4006-776-356 出国就医服务电话

免费获得国外相关药品，最快 1 个工作日回馈药物信息

出境医 / 临床实验 / Flublok or Fluzone With Advax-CpG55.2 or AF03

Flublok or Fluzone With Advax-CpG55.2 or AF03

Study Description
Brief Summary:
This is a Phase I, randomized, double blinded, clinical trial in up to 240 males and non-pregnant females, 18-45 years of age, inclusive, who are in good health and meet all eligibility criteria. This clinical trial is designed to assess the safety, reactogenicity and immunogenicity of either the 2018/2019 seasonal Fluzone or Flublok Quadrivalent Influenza Vaccine (QIV) manufactured by Sanofi Pasteur (SP) given without adjuvant or with one of two adjuvant formulations, AF03 or Advax-CpG55.2. Eight Vaccine and Treatment Evaluation Unit (VTEU) sites will be included in the study. Study duration is approximately 18 months, and subject participation duration is 12 months. The primary objectives of this study are: 1) to assess the safety and reactogenicity of 2018/2019 Fluzone and Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 2) to assess the serum hemagglutination inhibition (HAI) antibody responses against 2018/2019 QIV strains from baseline (Day 1) to approximately Day 29 after receipt of 2018/2019 Fluzone and Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 3) to assess the serum neuraminidase inhibition antibody (NAI) responses by enzyme-linked lectin assay (ELLA) against NA antigens in the 2018/2019 QIV from baseline (Day 1) to approximately Day 29 after receipt of 2018/2019 Fluzone and Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 4) to assess the influenza neutralizing (Neut) antibody titer responses against 2018/2019 QIV strains from baseline (Day 1) to approximately Day 29 after receipt of 2018/2019 Fluzone and Flublok with and without AF03 or Advax- CpG55.2 adjuvant.

Condition or disease Intervention/treatment Phase
Influenza Influenza Immunisation Drug: AF03 Biological: Delta Inulin-CpG55.2 Biological: Influenza Virus Quadrivalent Inactivated Vaccine Biological: Quadrivalent Recombinant Seasonal Influenza Vaccine Phase 1

Detailed Description:
This is a Phase I, randomized, double blinded, clinical trial in up to 240 males and non-pregnant females, 18-45 years of age, inclusive, who are in good health and meet all eligibility criteria. This clinical trial is designed to assess the safety, reactogenicity and immunogenicity of either the 2018/2019 seasonal Fluzone or Flublok Quadrivalent Influenza Vaccine (QIV) manufactured by Sanofi Pasteur (SP) given without adjuvant or with one of two adjuvant formulations, AF03 or Advax-CpG55.2. Subjects will be stratified by prior receipt of licensed, seasonal influenza vaccine (defined as receipt of at least one of the 2017/2018 and/or 2018/2019 influenza vaccines) and will be randomly assigned to 1 of 6 treatment arms to receive a single dose of one of the two seasonal 2018/2019 QIV vaccine formulations with or without one of the two adjuvants (Day 1). On approximately Day 90, each subject will receive a single dose of the seasonal 2019/2020 QIV. Groups 1, 2 and 3 will receive 2019/2020 Fluzone QIV and Groups 4, 5 and 6 will receive 2019/2020 Flublok QIV. Eight Vaccine and Treatment Evaluation Unit (VTEU) sites will be included in the study. Study duration is approximately 18 months, and subject participation duration is 12 months. The primary objectives of this study are: 1) to assess the safety and reactogenicity of 2018/2019 Fluzone and Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 2) to assess the serum hemagglutination inhibition (HAI) antibody responses against 2018/2019 QIV strains from baseline (Day 1) to approximately Day 29 after receipt of 2018/2019 Fluzone and Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 3) to assess the serum neuraminidase inhibition antibody (NAI) responses by enzyme-linked lectin assay (ELLA) against NA antigens in the 2018/2019 QIV from baseline (Day 1) to approximately Day 29 after receipt of 2018/2019 Fluzone and Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 4) to assess the influenza neutralizing (Neut) antibody titer responses against 2018/2019 QIV strains from baseline (Day 1) to approximately Day 29 after receipt of 2018/2019 Fluzone and Flublok with and without AF03 or Advax- CpG55.2 adjuvant. The secondary objectives of this study are: 1) to assess protocol specified adverse events of special interest (AESI), medically-attended adverse events (MAAEs), including new-onset chronic medical conditions (NOCMCs) and potentially immune-mediated medical conditions (PIMMCs) that occur after receipt of study product; 2) to assess the HAI, Neut and NAI ELLA responses to the 2019/2020 QIV strains prior to (Day 1) and approximately 28 days after vaccination with the 2019/2020 QIV in all study groups; 3) to assess the HAI antibody responses against heterologous influenza A/H1 and H3 strains from baseline (Day 1) to approximately Days 8, 29, 57, 90 and 118 after receipt of 2018/2019 Fluzone or Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 4) to assess NAI ELLA responses against heterologous N1 and N2 NA antigens from baseline (Day 1) to approximately Days 8, 29, 57, 90 and 118 after administration of 2018/2019 Fluzone with and without AF03 or Advax-CpG55.2 adjuvant; 5) to assess the influenza neutralizing (Neut) antibody titer responses against heterologous influenza A/H1 and H3 strains from baseline (Day 1) to approximately Days 8, 29, 57, 90 and 118 after administration of 2018/2019 Fluzone and Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 6) to assess the longitudinal kinetics and durability of the HAI, NAI, and Neut responses against the 2018/2019 QIV strains on approximately Days 8, 57, 90 and 118 following receipt of the 2018/2019 Fluzone and Flublok with and without AF03 or Advax-CpG55.2 adjuvant.
Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 241 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: A Phase I Study to Assess the Safety, Reactogenicity and Immunogenicity of Two Quadrivalent Seasonal Influenza Vaccines (Fluzone(R) or Flublok(R)) With or Without One of Two Adjuvants (AF03 or Advax-CpG55.2) in Healthy Adults 18-45 Years of Age
Actual Study Start Date : June 10, 2019
Actual Primary Completion Date : September 18, 2020
Actual Study Completion Date : September 18, 2020
Arms and Interventions
Arm Intervention/treatment
Experimental: Group 1
0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90, n=40
 Biological: Influenza Virus Quadrivalent Inactivated Vaccine
2018/2019 Fluzone QIV and 2019/2020 Fluzone QIV vaccines will be given with 90 days interval
Experimental: Group 2
0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90, n=40
 Drug: AF03
A squalene-in-PBS emulsion stabilized by nonionic surfactants, sorbitan oleate and macrogol cetostearyl ether

Biological: Influenza Virus Quadrivalent Inactivated Vaccine
2018/2019 Fluzone QIV and 2019/2020 Fluzone QIV vaccines will be given with 90 days interval
Experimental: Group 3
0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90, n=40
 Biological: Delta Inulin-CpG55.2
A combination adjuvant supplied as two separate components, Delta Inulin (Sypharma Pty Ltd.) and CpG55.2 (Nikko Denka Avecia and Sypharma Pty Ltd)

Biological: Influenza Virus Quadrivalent Inactivated Vaccine
2018/2019 Fluzone QIV and 2019/2020 Fluzone QIV vaccines will be given with 90 days interval
Experimental: Group 4
0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90, n=40
 Biological: Quadrivalent Recombinant Seasonal Influenza Vaccine
2018/2019 Flublok QIV and 2019/2020 Flublok QIV vaccines will be given with 90 days interval
Experimental: Group 5
0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90, n=40
 Drug: AF03
A squalene-in-PBS emulsion stabilized by nonionic surfactants, sorbitan oleate and macrogol cetostearyl ether

Biological: Quadrivalent Recombinant Seasonal Influenza Vaccine
2018/2019 Flublok QIV and 2019/2020 Flublok QIV vaccines will be given with 90 days interval
Experimental: Group 6
0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90, n=40
 Biological: Delta Inulin-CpG55.2
A combination adjuvant supplied as two separate components, Delta Inulin (Sypharma Pty Ltd.) and CpG55.2 (Nikko Denka Avecia and Sypharma Pty Ltd)

Biological: Quadrivalent Recombinant Seasonal Influenza Vaccine
2018/2019 Flublok QIV and 2019/2020 Flublok QIV vaccines will be given with 90 days interval
Outcome Measures
Primary Outcome Measures :
  1. Geometric mean fold rise (GMFR) in hemagglutination inhibition (HAI) titers against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 29 ]
  2. Geometric mean fold rise (GMFR) in neuraminidase inhibition (NAI) titers against neuraminidase (NA) antigens in the 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 29 ]
  3. Geometric mean fold rise (GMFR) in neutralizing (Neut) titers against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 1 through Day 29 ]
  4. Geometric mean titers (GMTs) of serum hemagglutination inhibition (HAI) against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) strain [ Time Frame: Day 1 through Day 29 ]
  5. Occurrence of abnormal clinical safety laboratory adverse events (AEs) [ Time Frame: Day 1 through Day 8 ]
  6. Occurrence of all serious adverse events (SAEs) [ Time Frame: Day 1 through Day 365 ]
  7. Occurrence of solicited reactogenicity events [ Time Frame: Day 1 through Day 8 ]
    Both local and systemic AEs will be assessed

  8. Occurrence of unsolicited adverse events (AEs) [ Time Frame: Day 1 through Day 29 ]
  9. Percentage of subjects achieving hemagglutination inhibition (HAI) titer seroconversion against 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 29 ]
    HAI seroconversion defined as either a pre-vaccination titer < 1:10 and a post-vaccination titer >/= 1:40 or a pre-vaccination titer >/= 1:10 and a minimum four-fold rise in post-vaccination antibody titer.

  10. Percentage of subjects achieving neuraminidase inhibition (NAI) seroconversion [ Time Frame: Day 29 ]
    NAI seroconversion defined as >/= 4-fold rise in post vaccination antibody titers against the NA antigens in the 2018/2019 QIV.

  11. Percentage of subjects achieving neutralizing (Neut) titer seroconversion against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 29 ]
    Neut titer seroconversion defined as either a pre-vaccination titer < 1:10 and a post-vaccination titer >/= 1:40 or a pre-vaccination titer >/= 1:10 and a minimum four-fold rise in post-vaccination antibody titer.

  12. Percentage of subjects with a neutralizing (Neut) titer >/= 1:40 against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 1 through Day 29 ]
  13. Percentage of subjects with hemagglutination inhibition (HAI) titer >/= 1:40 against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 1 through Day 29 ]
  14. Ratio of geometric mean titers (GMTs) of serum hemagglutination inhibition (HAI) against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains between adjuvanted and unadjuvanted study groups [ Time Frame: Day 1 through Day 29 ]
  15. Ratio of serum neuraminidase inhibition (NAI) geometric mean titer (GMT) between adjuvanted and unadjuvanted study groups [ Time Frame: Day 1 through Day 29 ]
  16. Ratio of serum neutralizing (Neut) geometric mean titer (GMT) between adjuvanted and unadjuvanted study groups [ Time Frame: Day 1 through Day 29 ]
  17. Serum neuraminidase inhibition (NAI) geometric mean titer (GMT) [ Time Frame: Day 1 through Day 29 ]
  18. Serum neutralizing (Neut) geometric mean titer (GMT) [ Time Frame: Day 1 through Day 29 ]

Secondary Outcome Measures :
  1. Geometric mean fold rise (GMFR) in hemagglutination inhibition (HAI) against heterologous H1 and H3 influenza strains [ Time Frame: Day 1 through Day 118 ]
  2. Geometric mean fold rise (GMFR) in hemagglutination inhibition (HAI) titers against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 1 through Day 118 ]
  3. Geometric mean fold rise (GMFR) in neuraminidase inhibition (NAI) titers against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 1 through Day 118 ]
    NAI titers will only be assessed on study groups 1, 2, and 3.

  4. Geometric mean fold rise (GMFR) in neutralizing (Neut) titers against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 1 through Day 118 ]
  5. Geometric mean fold rise (GMFR) in serum neuraminidase inhibition (NAI) against heterologous N1 and N2 neuraminidase (NA) antigens [ Time Frame: Day 1 through Day 118 ]
    NAI titers will only be assessed on study groups 1, 2, and 3.

  6. Geometric mean fold rise (GMFR) of neutralizing (Neut) antibody titers against heterologous H1 and H3 influenza strains [ Time Frame: Day 1 through Day 118 ]
  7. Occurrence of protocol specified adverse events of special interests (AESIs) [ Time Frame: Day 1 through Day 365 ]
  8. Occurrence of protocol specified medically-attended adverse events (MAAEs [ Time Frame: Day 1 through Day 365 ]
    Including new-onset chronic medical conditions (NOCMCs) and potentially immune-mediated medical conditions (PIMMCs)

  9. Percentage of subjects achieving a hemagglutination inhibition (HAI) titer >/= 1:40 against 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 8 through Day 118 ]
  10. Percentage of subjects achieving a hemagglutination inhibition (HAI) titer >/= 1:40 against 2019/2020 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 90 through Day 118 ]
  11. Percentage of subjects achieving a hemagglutination inhibition (HAI) titer >/= 1:40 against heterologous H1 and H3 influenza strains [ Time Frame: Day 1 through Day 118 ]
  12. Percentage of subjects achieving hemagglutination inhibition (HAI) titer seroconversion against 2018/2019 Quadrivalent Influenza Vaccine (QIV) antigens and strains [ Time Frame: Day 8 through Day 118 ]
  13. Percentage of subjects achieving hemagglutination inhibition (HAI) titer seroconversion against 2019/2020 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 118 ]
  14. Percentage of subjects achieving hemagglutination inhibition (HAI) titer seroconversion against heterologous H1 and H3 influenza strains [ Time Frame: Day 8 through Day 118 ]
  15. Percentage of subjects achieving neuraminidase inhibition (NAI) titer seroconversion against 2018/2019 Quadrivalent Influenza Vaccine (QIV) antigens and strains [ Time Frame: Day 8 through Day 118 ]
    NAI titers will only be assessed on study groups 1, 2, and 3.

  16. Percentage of subjects achieving neuraminidase inhibition (NAI) titer seroconversion against 2019/2020 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 118 ]
    NAI titers will only be assessed on study groups 1, 2, and 3.

  17. Percentage of subjects achieving neutralizing (Neut) titer >/= 1:40 against 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 8 through Day 118 ]
  18. Percentage of subjects achieving neutralizing (Neut) titer seroconversion against 2018/2019 Quadrivalent Influenza Vaccine (QIV) antigens and strains [ Time Frame: Day 8 through Day 118 ]
  19. Percentage of subjects achieving neutralizing (Neut) titer seroconversion against 2019/2020 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 118 ]
  20. Percentage of subjects achieving neutralizing (Neut) titer seroconversion against heterologous H1 and H3 influenza strains [ Time Frame: Day 8 through Day 118 ]
  21. Percentage of subjects achieving seroconversion against heterologous N1 and N2 neuraminidase (NA) antigens [ Time Frame: Day 8 through Day 118 ]
    NA antigens will only be assessed on study groups 1, 2, and 3.

  22. Ratio of serum hemagglutination inhibition (HAI) geometric mean titer (GMT) against 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains between adjuvanted and unadjuvanted study groups [ Time Frame: Day 8 through Day 118 ]
  23. Ratio of serum hemagglutination inhibition (HAI) geometric mean titer (GMT) against heterologous H1 and H3 influenza strains between adjuvanted and unadjuvanted study groups [ Time Frame: Day 1 through Day 118 ]
  24. Ratio of serum hemagglutination inhibition (HAI) geometric mean titers (GMTs) against 2019/2020 Quadrivalent Influenza Vaccine (QIV) strains between adjuvanted and unadjuvanted study groups [ Time Frame: Day 90 through Day 118 ]
  25. Ratio of serum neuraminidase inhibition (NAI) geometric mean titer (GMT) against 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains between adjuvanted and unadjuvanted study groups [ Time Frame: Day 8 through Day 118 ]
    NAI titers will only be assessed on study groups 1, 2, and 3.

  26. Ratio of serum neuraminidase inhibition (NAI) geometric mean titers (GMTs) against 2019/2020 Quadrivalent Influenza Vaccine (QIV) strains between adjuvanted and unadjuvanted study groups [ Time Frame: Day 90 through Day 118 ]
    NAI titers will only be assessed on study groups 1, 2, and 3.

  27. Ratio of serum neuraminidase inhibition (NAI) geometric mean titers (GMTs) against heterologous N1 and N2 neuraminidase (NA) antigens between adjuvanted and unadjuvanted study groups [ Time Frame: Day 1 through Day 118 ]
    NAI titers will only be assessed on study groups 1, 2, and 3.

  28. Ratio of serum neutralizing (Neut) geometric mean titer (GMT) against 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains between adjuvanted and unadjuvanted study groups [ Time Frame: Day 8 through Day 118 ]
  29. Ratio of serum neutralizing (Neut) geometric mean titers (GMTs) against 2019/2020 Quadrivalent Influenza Vaccine (QIV) strains between adjuvanted and unadjuvanted study groups [ Time Frame: Day 90 through Day 118 ]
  30. Ratio of serum neutralizing (Neut) geometric mean titers (GMTs) against heterologous H1 and H3 influenza strains between adjuvanted and unadjuvanted study groups [ Time Frame: Day 1 through Day 118 ]
  31. Serum hemagglutination inhibition (HAI) geometric mean fold rise (GMFR) against 2019/2020 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 90 through Day 118 ]
  32. Serum hemagglutination inhibition (HAI) geometric mean titer (GMT) against 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 8 through Day 118 ]
  33. Serum hemagglutination inhibition (HAI) geometric mean titer (GMT) against heterologous H1 and H3 influenza strains [ Time Frame: Day 1 through Day 118 ]
  34. Serum hemagglutination inhibition (HAI) geometric mean titers (GMTs) against 2019/2020 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 90 through Day 118 ]
  35. Serum neuraminidase inhibition (NAI) geometric mean fold rise (GMFR) against 2019/2020 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 90 through Day 118 ]
    NAI titers will only be assessed on study groups 1, 2, and 3.

  36. Serum neuraminidase inhibition (NAI) geometric mean titer (GMT) against 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 8 through Day 118 ]
    NAI titers will only be assessed on study groups 1, 2, and 3.

  37. Serum neuraminidase inhibition (NAI) geometric mean titers (GMTs) against 2019/2020 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 90 through Day 118 ]
    NAI titers will only be assessed on study groups 1, 2, and 3.

  38. Serum neuraminidase inhibition (NAI) geometric mean titers (GMTs) against heterologous N1 and N2 neuraminidase (NA) antigens [ Time Frame: Day 1 through Day 118 ]
    NAI titers will only be assessed on study groups 1, 2, and 3.

  39. Serum neutralizing (Neut) geometric mean fold rise (GMFR) against 2019/2020 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 90 through Day 118 ]
  40. Serum neutralizing (Neut) geometric mean titer (GMT) against 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 8 through Day 118 ]
  41. Serum neutralizing (Neut) geometric mean titer (GMT) against heterologous H1 and H3 influenza strains [ Time Frame: Day 1 through 118 ]
  42. Serum neutralizing (Neut) geometric mean titers (GMTs) against 2019/2020 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 90 through Day 118 ]

Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Provide written informed consent prior to initiation of any study procedures.
  2. Are able to understand and comply with planned study procedures and be available for all study visits.
  3. Must agree to the collection of venous blood per protocol.
  4. Are males or non-pregnant females, 18 to 45 years of age, inclusive at time of enrollment.
  5. Are in good health*. *As determined by medical history and physical examination to evaluate acute or currently ongoing chronic medical or psychiatric diagnoses or conditions, defined as those that have been present for at least 90 days, which would affect the assessment of the safety of subjects or the immunogenicity of study vaccinations. Chronic medical diagnoses or conditions should be stable for the last 60 days (no hospitalizations, emergency room or urgent care for condition, or invasive medical procedure and no adverse symptoms that need medical intervention such as medication change/supplemental oxygen). This includes no change in chronic prescription medication, dose or in the 60 days prior to enrollment. Any prescription change that is due to change of health care provider, insurance company, etc., or that is done for financial reasons, as long as in the same class of medication, will not be considered a deviation of this inclusion criterion. Subjects may be on chronic or as needed (prn) medications if, in the opinion of the site PI or appropriate sub-investigator, they pose no additional risk to subject safety or assessment of reactogenicity and immunogenicity and do not indicate a worsening or treatment of continued symptoms of medical diagnosis or condition. Note: Low dose topical, corticosteroids as outlined in the Subject Exclusion Criteria as well as herbals, vitamins and supplements are permitted.
  6. Oral temperature is less than 100.0 degrees Fahrenheit.
  7. Pulse is 47 to 100 beats per minute, inclusive.
  8. Systolic blood pressure is 85 to 140 mmHg, inclusive.
  9. Diastolic blood pressure is 55 to 90 mmHg, inclusive.

  10. Screening laboratories (Erythrocyte Sedimentation Rate (ESR), White Blood Cells (WBC), Hemoglobin (Hgb), Platelets (PLTs), Alanine Aminotransferase (ALT), Total Bilirubin (T. Bili), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase (GGT), Alkaline Phosphatase (ALP) serum lipase, serum amylase and Creatinine (Cr)) are within acceptable parameters*.

    *ESR must be below 30 mm/hr; WBC >3.90 K/MM3 and <10.60 K/MM3; Hgb >/= 11.5 g/dl (women) or >/= 12.5 g/dl (men); PLTs (EDTA) 140-415 K/MM3; PLTs (Citrate) 125-325 K/MM3 ALT </= 43 U/L (women) or </= 60 U/L (men); T Bili </=1.20 mg/dl; Cr < 1.1 mg/dl (women) or < 1.4 mg/dl (men); AST 10-36 U/L (women) or 10-43 U/L (men); GGT 5--32 U/L (women) or 10-49 U/L (men); ALP 30-115 U/L (women) or 43-115 U/L (men); lipase 13-60 U/L; amylase (Total) 35-121 U/L, for subjects to qualify for randomization and vaccination.

  11. Women of childbearing potential* must use an acceptable contraception method** from at least 30 days before the first study vaccination until 60 days after the second study vaccination.

    *Not sterilized via bilateral oophorectomy, tubal ligation/ salpingectomy, hysterectomy, or successful Essure(R) placement (permanent, non-surgical, non-hormonal sterilization) with documented radiological confirmation test at least 90 days after the procedure, and still menstruating or <1 year has passed since the last menses if menopausal.

    • Includes non-male sexual relationships, full abstinence from sexual intercourse with a male partner, monogamous relationship with vasectomized partner who has been vasectomized for 180 days or more and shown to be azoospermic prior to the subject receiving the study vaccination, barrier methods such as condoms or diaphragms/cervical cap with spermicide, effective intrauterine devices, NuvaRing(R), and licensed hormonal methods such as implants, injectables or oral contraceptives ("the pill").
  12. Women of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to the first study vaccination.
  13. For a woman with potential to become pregnant, she understands that in the event of pregnancy during the study she will be approached to enroll in the Sanofi Pregnancy Registry.
  14. Must agree to have residual specimens (i.e. residual/excess of per protocol specifications).

Exclusion Criteria:

  1. Have an acute illness*, as determined by the site Principal Investigator (PI) or appropriate sub-investigator, within 72 hours prior to study vaccination.

    *An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the site PI or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol.

  2. Have any medical disease or condition that, in the opinion of the site PI or appropriate sub-investigator, is a contraindication to study participation*.

    *Including acute, subacute, intermittent or chronic medical disease or condition that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this trial.

  3. Have immunosuppression as a result of an underlying illness or treatment, a recent history or current use of immunosuppressive or immunomodulating disease therapy.
  4. Use of anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior to study vaccination.
  5. Have known active or recently active (12 months) neoplastic disease or a history of any hematologic malignancy. Non-melanoma, treated, skin cancers are permitted.
  6. Have known human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection.
  7. Have known hypersensitivity or allergy to eggs, egg or chicken protein, squalene-based adjuvants, or other components of the study vaccine.
  8. Have a history of severe reactions following previous immunization with licensed or unlicensed influenza vaccines.
  9. Have a history of Guillain-Barré Syndrome (GBS).
  10. Have a history of convulsions or encephalomyelitis within 90 days prior to study vaccination.
  11. Have a history of Potentially Immune-Mediated Medical Conditions (PIMMCs).
  12. Have a history of alcohol or drug abuse within 5 years prior to study vaccination.

  13. Have any diagnosis, current or past, of schizophrenia, bipolar disease or other psychiatric diagnosis that may interfere* with subject compliance or safety evaluations.

    *As determined by the site PI or appropriate sub-investigator.

  14. Have been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others within 5 years prior to study vaccination.
  15. Have taken oral or parenteral (including intra-articular) corticosteroids of any dose within 30 days prior to study vaccination.

  16. Have taken high-dose inhaled corticosteroids* within 30 days prior to study vaccination.

    *High-dose defined as per age as using inhaled high-dose per reference chart in the National Heart, Lung and Blood Institute Guidelines for the Diagnosis and Management of Asthma (EPR-3) or other lists published in UPTODATE.

  17. Received or plan to receive a licensed, live vaccine (excluding all licensed, seasonal LAIVs) within 30 days before or after the study vaccination.
  18. Received or plan to receive a licensed, inactivated vaccine (excluding all licensed, seasonal IIVs) within 14 days before or after each study vaccination.
  19. Have received any 2018/2019 seasonal influenza vaccine within the 6 months prior to enrollment.
  20. Plans to receive any 2019/2020 seasonal influenza vaccine within approximately 90 days of receipt of the first study vaccination.
  21. Have a known history of documented influenza infection within the past 6 months.
  22. Received immunoglobulin or other blood products (except Rho D immunoglobulin) within 90 days prior to study vaccination.

  23. Received an experimental agent* within 30 days prior to the study vaccination or expect to receive another experimental agent* during the trial-reporting period*.

    *Including vaccine, drug, biologic, device, blood product, or medication.

    **Other than from participation in this trial.

    ***Approximately 12 months after the first study vaccination.

  24. Are participating or plan to participate in another clinical trial with an interventional agent* that will be received during the trial-reporting period**.

    *Including licensed or unlicensed vaccine, drug, biologic, device, blood product, or medication.

    **Approximately 12 months after the first study vaccination.

  25. Female subjects who are breastfeeding or plan to breastfeed from the time of the first study vaccination through 30 days after the last study vaccination.
  26. Plan to travel outside the US (continental US, Hawaii and Alaska) from the time of study vaccination through approximately 90 days after the first study vaccination.
  27. Planning to donate blood within 4 months following first vaccination.

Exclusion Criteria for Second Study Vaccination:

All study participants will be expected to receive the second study vaccination except under the circumstances listed below. The second study vaccination will not be administered to a subject if any of the following criteria are met:

  • Meets the contraindication on the package insert to receipt of licensed influenza vaccine.
  • As deemed necessary by the site principal investigator or appropriate sub-investigator for noncompliance or other reasons.
  • Subject refusal of further study vaccination.
  • Withdrawal of consent.
  • Subject is lost to follow-up.
  • Termination of this trial.
  • New information becomes available that makes further participation unsafe.
Contacts and Locations

Locations
Layout table for location information
United States, Georgia
Emory Children's Center - Pediatric Infectious Diseases
Atlanta, Georgia, United States, 30322-1014
United States, Iowa
University of Iowa - Vaccine Research and Education Unit
Iowa City, Iowa, United States, 52242-2600
United States, Maryland
University of Maryland Baltimore - School of Medicine - Medicine
Baltimore, Maryland, United States, 21201-1509
United States, Missouri
Saint Louis University - Center for Vaccine Development
Saint Louis, Missouri, United States, 63104-1015
United States, North Carolina
Duke Human Vaccine Institute - Duke Vaccine and Trials Unit
Durham, North Carolina, United States, 27704
United States, Ohio
Cincinnati Children's Hospital Medical Center - Infectious Diseases
Cincinnati, Ohio, United States, 45229-3039
United States, Tennessee
Vanderbilt University - Pediatric - Vanderbilt Vaccine Research Center
Nashville, Tennessee, United States, 37232-2573
United States, Texas
Baylor College of Medicine - Molecular Virology and Microbiology
Houston, Texas, United States, 77030-3411
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Tracking Information
First Submitted Date  ICMJE May 9, 2019
First Posted Date  ICMJE May 10, 2019
Last Update Posted Date March 2, 2021
Actual Study Start Date  ICMJE June 10, 2019
Actual Primary Completion Date September 18, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 25, 2021)
  • Geometric mean fold rise (GMFR) in hemagglutination inhibition (HAI) titers against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 29 ]
  • Geometric mean fold rise (GMFR) in neuraminidase inhibition (NAI) titers against neuraminidase (NA) antigens in the 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 29 ]
  • Geometric mean fold rise (GMFR) in neutralizing (Neut) titers against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 1 through Day 29 ]
  • Geometric mean titers (GMTs) of serum hemagglutination inhibition (HAI) against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) strain [ Time Frame: Day 1 through Day 29 ]
  • Occurrence of abnormal clinical safety laboratory adverse events (AEs) [ Time Frame: Day 1 through Day 8 ]
  • Occurrence of all serious adverse events (SAEs) [ Time Frame: Day 1 through Day 365 ]
  • Occurrence of solicited reactogenicity events [ Time Frame: Day 1 through Day 8 ]
    Both local and systemic AEs will be assessed
  • Occurrence of unsolicited adverse events (AEs) [ Time Frame: Day 1 through Day 29 ]
  • Percentage of subjects achieving hemagglutination inhibition (HAI) titer seroconversion against 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 29 ]
    HAI seroconversion defined as either a pre-vaccination titer < 1:10 and a post-vaccination titer >/= 1:40 or a pre-vaccination titer >/= 1:10 and a minimum four-fold rise in post-vaccination antibody titer.
  • Percentage of subjects achieving neuraminidase inhibition (NAI) seroconversion [ Time Frame: Day 29 ]
    NAI seroconversion defined as >/= 4-fold rise in post vaccination antibody titers against the NA antigens in the 2018/2019 QIV.
  • Percentage of subjects achieving neutralizing (Neut) titer seroconversion against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 29 ]
    Neut titer seroconversion defined as either a pre-vaccination titer < 1:10 and a post-vaccination titer >/= 1:40 or a pre-vaccination titer >/= 1:10 and a minimum four-fold rise in post-vaccination antibody titer.
  • Percentage of subjects with a neutralizing (Neut) titer >/= 1:40 against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 1 through Day 29 ]
  • Percentage of subjects with hemagglutination inhibition (HAI) titer >/= 1:40 against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 1 through Day 29 ]
  • Ratio of geometric mean titers (GMTs) of serum hemagglutination inhibition (HAI) against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains between adjuvanted and unadjuvanted study groups [ Time Frame: Day 1 through Day 29 ]
  • Ratio of serum neuraminidase inhibition (NAI) geometric mean titer (GMT) between adjuvanted and unadjuvanted study groups [ Time Frame: Day 1 through Day 29 ]
  • Ratio of serum neutralizing (Neut) geometric mean titer (GMT) between adjuvanted and unadjuvanted study groups [ Time Frame: Day 1 through Day 29 ]
  • Serum neuraminidase inhibition (NAI) geometric mean titer (GMT) [ Time Frame: Day 1 through Day 29 ]
  • Serum neutralizing (Neut) geometric mean titer (GMT) [ Time Frame: Day 1 through Day 29 ]
Original Primary Outcome Measures  ICMJE
 (submitted: May 9, 2019)
  • Geometric mean fold rise (GMFR) in Hemagglutination Inhibition (HAI) antibodies against the 2018/2019 QIV strains [ Time Frame: Day 1 through Day 29 ]
  • Geometric mean fold rise (GMFR) in Neuraminidase Inhibition (NAI)in subjects receiving Fluzone injection [ Time Frame: Day 1 through Day 29 ]
  • Geometric mean fold rise (GMFR) in titers against the 2018/2019 QIV strains [ Time Frame: Day 1 through Day 90 ]
  • Geometric mean titers (GMT) of serum Neutralizing (Neut) antibodies against heterologous H3 influenza strains [ Time Frame: From Day 1 through Day 365 ]
  • Geometric mean titers (GMTs) of serum antibodies against the 2018/2019 QIV strains [ Time Frame: From Day 1 through Day 365 ]
  • Geometric mean titers (GMTs) of serum Hemagglutination Inhibition (HAI) antibodies against the 2018/2019 QIV strain [ Time Frame: Day 1 through Day 29 ]
  • Geometric mean titers (GMTs) of serum Hemagglutination Inhibition (HAI) antibodies against the heterologous H3 influenza strains [ Time Frame: From Day 1 through Day 365 ]
  • Geometric mean titers (GMTs) of serum Neuraminidase Inhibition (NAI) antibodies against the heterologous N1 and N2 Neuraminidase (NA) influenza strains in subjects receiving Fluzone injection [ Time Frame: From Day 1 through Day 365 ]
  • Occurrence of abnormal clinical safety laboratory adverse events (AEs) [ Time Frame: Day 1 through Day 8 ]
  • Occurrence of all serious adverse events (SAEs) [ Time Frame: Day 1 through Day 366 ]
  • Occurrence of solicited reactogenicity events [ Time Frame: Day 1 through Day 8 ]
  • Occurrence of unsolicited adverse events [ Time Frame: Day 1 through Day 29 ]
  • Percentage of subjects achieving Hemagglutination Inhibition (HAI) seroconversion against 2018/2019 QIV strains (pre-vaccination titer <1:10 and post-vacc. titer = / >1:40 or pre-vacc. titer = / >1:10 and min. 4-fold rise in post-vacc. antibody titer) [ Time Frame: Day 1 through Day 29 ]
  • Percentage of subjects achieving Hemagglutination Inhibition (HAI) titer = / > 1:40 against heterologous H3 influenza strains [ Time Frame: From Day 1 through Day 365 ]
  • Percentage of subjects achieving Neuraminidase Inhibition (NAI) seroconversion (defined as = / > 4-fold rise in post vaccination antibody titers against the Neuraminidase (NA) antigens in the 2018/2019 QIV) [ Time Frame: Day 1 through Day 29 ]
  • Percentage of subjects achieving Neutralizing (Neut) titer seroconversion against heterologous H3 influenza strains [ Time Frame: From Day 1 through Day 365 ]
  • Percentage of subjects achieving seroconversion against 2018/2019 QIV Neuraminidase (NA) antigens and strains [ Time Frame: From Day 1 through Day 365 ]
  • Percentage of subjects achieving seroconversion against heterologous N1 and N2 Neuraminidase (NA) antigens in subjects receiving Fluzone injection [ Time Frame: From Day 1 through Day 365 ]
  • Percentage of subjects achieving titer = / > 1:40 against 2018/2019 QIV strains [ Time Frame: From Day 1 through Day 365 ]
  • Percentage of subjects with Hemagglutination Inhibition (HAI) titer = / > 1:40 against the 2018/2019 QIV strains [ Time Frame: Day 1 through Day 29 ]
  • Percentages of subjects achieving Hemagglutination Inhibition (HAI) titer seroconversion against heterologous H3 influenza strains [ Time Frame: From Day 1 through Day 365 ]
  • Serum neuraminidase inhibition (NAI) geometric mean titer (GMT) [ Time Frame: Day 1 through Day 29 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 25, 2021)
  • Geometric mean fold rise (GMFR) in hemagglutination inhibition (HAI) against heterologous H1 and H3 influenza strains [ Time Frame: Day 1 through Day 118 ]
  • Geometric mean fold rise (GMFR) in hemagglutination inhibition (HAI) titers against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 1 through Day 118 ]
  • Geometric mean fold rise (GMFR) in neuraminidase inhibition (NAI) titers against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 1 through Day 118 ]
    NAI titers will only be assessed on study groups 1, 2, and 3.
  • Geometric mean fold rise (GMFR) in neutralizing (Neut) titers against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 1 through Day 118 ]
  • Geometric mean fold rise (GMFR) in serum neuraminidase inhibition (NAI) against heterologous N1 and N2 neuraminidase (NA) antigens [ Time Frame: Day 1 through Day 118 ]
    NAI titers will only be assessed on study groups 1, 2, and 3.
  • Geometric mean fold rise (GMFR) of neutralizing (Neut) antibody titers against heterologous H1 and H3 influenza strains [ Time Frame: Day 1 through Day 118 ]
  • Occurrence of protocol specified adverse events of special interests (AESIs) [ Time Frame: Day 1 through Day 365 ]
  • Occurrence of protocol specified medically-attended adverse events (MAAEs [ Time Frame: Day 1 through Day 365 ]
    Including new-onset chronic medical conditions (NOCMCs) and potentially immune-mediated medical conditions (PIMMCs)
  • Percentage of subjects achieving a hemagglutination inhibition (HAI) titer >/= 1:40 against 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 8 through Day 118 ]
  • Percentage of subjects achieving a hemagglutination inhibition (HAI) titer >/= 1:40 against 2019/2020 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 90 through Day 118 ]
  • Percentage of subjects achieving a hemagglutination inhibition (HAI) titer >/= 1:40 against heterologous H1 and H3 influenza strains [ Time Frame: Day 1 through Day 118 ]
  • Percentage of subjects achieving hemagglutination inhibition (HAI) titer seroconversion against 2018/2019 Quadrivalent Influenza Vaccine (QIV) antigens and strains [ Time Frame: Day 8 through Day 118 ]
  • Percentage of subjects achieving hemagglutination inhibition (HAI) titer seroconversion against 2019/2020 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 118 ]
  • Percentage of subjects achieving hemagglutination inhibition (HAI) titer seroconversion against heterologous H1 and H3 influenza strains [ Time Frame: Day 8 through Day 118 ]
  • Percentage of subjects achieving neuraminidase inhibition (NAI) titer seroconversion against 2018/2019 Quadrivalent Influenza Vaccine (QIV) antigens and strains [ Time Frame: Day 8 through Day 118 ]
    NAI titers will only be assessed on study groups 1, 2, and 3.
  • Percentage of subjects achieving neuraminidase inhibition (NAI) titer seroconversion against 2019/2020 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 118 ]
    NAI titers will only be assessed on study groups 1, 2, and 3.
  • Percentage of subjects achieving neutralizing (Neut) titer >/= 1:40 against 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 8 through Day 118 ]
  • Percentage of subjects achieving neutralizing (Neut) titer seroconversion against 2018/2019 Quadrivalent Influenza Vaccine (QIV) antigens and strains [ Time Frame: Day 8 through Day 118 ]
  • Percentage of subjects achieving neutralizing (Neut) titer seroconversion against 2019/2020 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 118 ]
  • Percentage of subjects achieving neutralizing (Neut) titer seroconversion against heterologous H1 and H3 influenza strains [ Time Frame: Day 8 through Day 118 ]
  • Percentage of subjects achieving seroconversion against heterologous N1 and N2 neuraminidase (NA) antigens [ Time Frame: Day 8 through Day 118 ]
    NA antigens will only be assessed on study groups 1, 2, and 3.
  • Ratio of serum hemagglutination inhibition (HAI) geometric mean titer (GMT) against 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains between adjuvanted and unadjuvanted study groups [ Time Frame: Day 8 through Day 118 ]
  • Ratio of serum hemagglutination inhibition (HAI) geometric mean titer (GMT) against heterologous H1 and H3 influenza strains between adjuvanted and unadjuvanted study groups [ Time Frame: Day 1 through Day 118 ]
  • Ratio of serum hemagglutination inhibition (HAI) geometric mean titers (GMTs) against 2019/2020 Quadrivalent Influenza Vaccine (QIV) strains between adjuvanted and unadjuvanted study groups [ Time Frame: Day 90 through Day 118 ]
  • Ratio of serum neuraminidase inhibition (NAI) geometric mean titer (GMT) against 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains between adjuvanted and unadjuvanted study groups [ Time Frame: Day 8 through Day 118 ]
    NAI titers will only be assessed on study groups 1, 2, and 3.
  • Ratio of serum neuraminidase inhibition (NAI) geometric mean titers (GMTs) against 2019/2020 Quadrivalent Influenza Vaccine (QIV) strains between adjuvanted and unadjuvanted study groups [ Time Frame: Day 90 through Day 118 ]
    NAI titers will only be assessed on study groups 1, 2, and 3.
  • Ratio of serum neuraminidase inhibition (NAI) geometric mean titers (GMTs) against heterologous N1 and N2 neuraminidase (NA) antigens between adjuvanted and unadjuvanted study groups [ Time Frame: Day 1 through Day 118 ]
    NAI titers will only be assessed on study groups 1, 2, and 3.
  • Ratio of serum neutralizing (Neut) geometric mean titer (GMT) against 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains between adjuvanted and unadjuvanted study groups [ Time Frame: Day 8 through Day 118 ]
  • Ratio of serum neutralizing (Neut) geometric mean titers (GMTs) against 2019/2020 Quadrivalent Influenza Vaccine (QIV) strains between adjuvanted and unadjuvanted study groups [ Time Frame: Day 90 through Day 118 ]
  • Ratio of serum neutralizing (Neut) geometric mean titers (GMTs) against heterologous H1 and H3 influenza strains between adjuvanted and unadjuvanted study groups [ Time Frame: Day 1 through Day 118 ]
  • Serum hemagglutination inhibition (HAI) geometric mean fold rise (GMFR) against 2019/2020 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 90 through Day 118 ]
  • Serum hemagglutination inhibition (HAI) geometric mean titer (GMT) against 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 8 through Day 118 ]
  • Serum hemagglutination inhibition (HAI) geometric mean titer (GMT) against heterologous H1 and H3 influenza strains [ Time Frame: Day 1 through Day 118 ]
  • Serum hemagglutination inhibition (HAI) geometric mean titers (GMTs) against 2019/2020 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 90 through Day 118 ]
  • Serum neuraminidase inhibition (NAI) geometric mean fold rise (GMFR) against 2019/2020 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 90 through Day 118 ]
    NAI titers will only be assessed on study groups 1, 2, and 3.
  • Serum neuraminidase inhibition (NAI) geometric mean titer (GMT) against 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 8 through Day 118 ]
    NAI titers will only be assessed on study groups 1, 2, and 3.
  • Serum neuraminidase inhibition (NAI) geometric mean titers (GMTs) against 2019/2020 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 90 through Day 118 ]
    NAI titers will only be assessed on study groups 1, 2, and 3.
  • Serum neuraminidase inhibition (NAI) geometric mean titers (GMTs) against heterologous N1 and N2 neuraminidase (NA) antigens [ Time Frame: Day 1 through Day 118 ]
    NAI titers will only be assessed on study groups 1, 2, and 3.
  • Serum neutralizing (Neut) geometric mean fold rise (GMFR) against 2019/2020 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 90 through Day 118 ]
  • Serum neutralizing (Neut) geometric mean titer (GMT) against 2018/2019 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 8 through Day 118 ]
  • Serum neutralizing (Neut) geometric mean titer (GMT) against heterologous H1 and H3 influenza strains [ Time Frame: Day 1 through 118 ]
  • Serum neutralizing (Neut) geometric mean titers (GMTs) against 2019/2020 Quadrivalent Influenza Vaccine (QIV) strains [ Time Frame: Day 90 through Day 118 ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Flublok or Fluzone With Advax-CpG55.2 or AF03
Official Title  ICMJE A Phase I Study to Assess the Safety, Reactogenicity and Immunogenicity of Two Quadrivalent Seasonal Influenza Vaccines (Fluzone(R) or Flublok(R)) With or Without One of Two Adjuvants (AF03 or Advax-CpG55.2) in Healthy Adults 18-45 Years of Age
Brief Summary This is a Phase I, randomized, double blinded, clinical trial in up to 240 males and non-pregnant females, 18-45 years of age, inclusive, who are in good health and meet all eligibility criteria. This clinical trial is designed to assess the safety, reactogenicity and immunogenicity of either the 2018/2019 seasonal Fluzone or Flublok Quadrivalent Influenza Vaccine (QIV) manufactured by Sanofi Pasteur (SP) given without adjuvant or with one of two adjuvant formulations, AF03 or Advax-CpG55.2. Eight Vaccine and Treatment Evaluation Unit (VTEU) sites will be included in the study. Study duration is approximately 18 months, and subject participation duration is 12 months. The primary objectives of this study are: 1) to assess the safety and reactogenicity of 2018/2019 Fluzone and Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 2) to assess the serum hemagglutination inhibition (HAI) antibody responses against 2018/2019 QIV strains from baseline (Day 1) to approximately Day 29 after receipt of 2018/2019 Fluzone and Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 3) to assess the serum neuraminidase inhibition antibody (NAI) responses by enzyme-linked lectin assay (ELLA) against NA antigens in the 2018/2019 QIV from baseline (Day 1) to approximately Day 29 after receipt of 2018/2019 Fluzone and Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 4) to assess the influenza neutralizing (Neut) antibody titer responses against 2018/2019 QIV strains from baseline (Day 1) to approximately Day 29 after receipt of 2018/2019 Fluzone and Flublok with and without AF03 or Advax- CpG55.2 adjuvant.
Detailed Description This is a Phase I, randomized, double blinded, clinical trial in up to 240 males and non-pregnant females, 18-45 years of age, inclusive, who are in good health and meet all eligibility criteria. This clinical trial is designed to assess the safety, reactogenicity and immunogenicity of either the 2018/2019 seasonal Fluzone or Flublok Quadrivalent Influenza Vaccine (QIV) manufactured by Sanofi Pasteur (SP) given without adjuvant or with one of two adjuvant formulations, AF03 or Advax-CpG55.2. Subjects will be stratified by prior receipt of licensed, seasonal influenza vaccine (defined as receipt of at least one of the 2017/2018 and/or 2018/2019 influenza vaccines) and will be randomly assigned to 1 of 6 treatment arms to receive a single dose of one of the two seasonal 2018/2019 QIV vaccine formulations with or without one of the two adjuvants (Day 1). On approximately Day 90, each subject will receive a single dose of the seasonal 2019/2020 QIV. Groups 1, 2 and 3 will receive 2019/2020 Fluzone QIV and Groups 4, 5 and 6 will receive 2019/2020 Flublok QIV. Eight Vaccine and Treatment Evaluation Unit (VTEU) sites will be included in the study. Study duration is approximately 18 months, and subject participation duration is 12 months. The primary objectives of this study are: 1) to assess the safety and reactogenicity of 2018/2019 Fluzone and Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 2) to assess the serum hemagglutination inhibition (HAI) antibody responses against 2018/2019 QIV strains from baseline (Day 1) to approximately Day 29 after receipt of 2018/2019 Fluzone and Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 3) to assess the serum neuraminidase inhibition antibody (NAI) responses by enzyme-linked lectin assay (ELLA) against NA antigens in the 2018/2019 QIV from baseline (Day 1) to approximately Day 29 after receipt of 2018/2019 Fluzone and Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 4) to assess the influenza neutralizing (Neut) antibody titer responses against 2018/2019 QIV strains from baseline (Day 1) to approximately Day 29 after receipt of 2018/2019 Fluzone and Flublok with and without AF03 or Advax- CpG55.2 adjuvant. The secondary objectives of this study are: 1) to assess protocol specified adverse events of special interest (AESI), medically-attended adverse events (MAAEs), including new-onset chronic medical conditions (NOCMCs) and potentially immune-mediated medical conditions (PIMMCs) that occur after receipt of study product; 2) to assess the HAI, Neut and NAI ELLA responses to the 2019/2020 QIV strains prior to (Day 1) and approximately 28 days after vaccination with the 2019/2020 QIV in all study groups; 3) to assess the HAI antibody responses against heterologous influenza A/H1 and H3 strains from baseline (Day 1) to approximately Days 8, 29, 57, 90 and 118 after receipt of 2018/2019 Fluzone or Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 4) to assess NAI ELLA responses against heterologous N1 and N2 NA antigens from baseline (Day 1) to approximately Days 8, 29, 57, 90 and 118 after administration of 2018/2019 Fluzone with and without AF03 or Advax-CpG55.2 adjuvant; 5) to assess the influenza neutralizing (Neut) antibody titer responses against heterologous influenza A/H1 and H3 strains from baseline (Day 1) to approximately Days 8, 29, 57, 90 and 118 after administration of 2018/2019 Fluzone and Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 6) to assess the longitudinal kinetics and durability of the HAI, NAI, and Neut responses against the 2018/2019 QIV strains on approximately Days 8, 57, 90 and 118 following receipt of the 2018/2019 Fluzone and Flublok with and without AF03 or Advax-CpG55.2 adjuvant.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Condition  ICMJE
  • Influenza
  • Influenza Immunisation
Intervention  ICMJE
  • Drug: AF03
    A squalene-in-PBS emulsion stabilized by nonionic surfactants, sorbitan oleate and macrogol cetostearyl ether
  • Biological: Delta Inulin-CpG55.2
    A combination adjuvant supplied as two separate components, Delta Inulin (Sypharma Pty Ltd.) and CpG55.2 (Nikko Denka Avecia and Sypharma Pty Ltd)
  • Biological: Influenza Virus Quadrivalent Inactivated Vaccine
    2018/2019 Fluzone QIV and 2019/2020 Fluzone QIV vaccines will be given with 90 days interval
  • Biological: Quadrivalent Recombinant Seasonal Influenza Vaccine
    2018/2019 Flublok QIV and 2019/2020 Flublok QIV vaccines will be given with 90 days interval
Study Arms  ICMJE
  • Experimental: Group 1
    0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90, n=40
    Intervention: Biological: Influenza Virus Quadrivalent Inactivated Vaccine
  • Experimental: Group 2
    0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90, n=40
    Interventions:
    • Drug: AF03
    • Biological: Influenza Virus Quadrivalent Inactivated Vaccine
  • Experimental: Group 3
    0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90, n=40
    Interventions:
    • Biological: Delta Inulin-CpG55.2
    • Biological: Influenza Virus Quadrivalent Inactivated Vaccine
  • Experimental: Group 4
    0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90, n=40
    Intervention: Biological: Quadrivalent Recombinant Seasonal Influenza Vaccine
  • Experimental: Group 5
    0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90, n=40
    Interventions:
    • Drug: AF03
    • Biological: Quadrivalent Recombinant Seasonal Influenza Vaccine
  • Experimental: Group 6
    0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90, n=40
    Interventions:
    • Biological: Delta Inulin-CpG55.2
    • Biological: Quadrivalent Recombinant Seasonal Influenza Vaccine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 10, 2019) 		241
Original Estimated Enrollment  ICMJE
 (submitted: May 9, 2019) 		240
Actual Study Completion Date  ICMJE September 18, 2020
Actual Primary Completion Date September 18, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Provide written informed consent prior to initiation of any study procedures.
  2. Are able to understand and comply with planned study procedures and be available for all study visits.
  3. Must agree to the collection of venous blood per protocol.
  4. Are males or non-pregnant females, 18 to 45 years of age, inclusive at time of enrollment.
  5. Are in good health*. *As determined by medical history and physical examination to evaluate acute or currently ongoing chronic medical or psychiatric diagnoses or conditions, defined as those that have been present for at least 90 days, which would affect the assessment of the safety of subjects or the immunogenicity of study vaccinations. Chronic medical diagnoses or conditions should be stable for the last 60 days (no hospitalizations, emergency room or urgent care for condition, or invasive medical procedure and no adverse symptoms that need medical intervention such as medication change/supplemental oxygen). This includes no change in chronic prescription medication, dose or in the 60 days prior to enrollment. Any prescription change that is due to change of health care provider, insurance company, etc., or that is done for financial reasons, as long as in the same class of medication, will not be considered a deviation of this inclusion criterion. Subjects may be on chronic or as needed (prn) medications if, in the opinion of the site PI or appropriate sub-investigator, they pose no additional risk to subject safety or assessment of reactogenicity and immunogenicity and do not indicate a worsening or treatment of continued symptoms of medical diagnosis or condition. Note: Low dose topical, corticosteroids as outlined in the Subject Exclusion Criteria as well as herbals, vitamins and supplements are permitted.
  6. Oral temperature is less than 100.0 degrees Fahrenheit.
  7. Pulse is 47 to 100 beats per minute, inclusive.
  8. Systolic blood pressure is 85 to 140 mmHg, inclusive.
  9. Diastolic blood pressure is 55 to 90 mmHg, inclusive.

  10. Screening laboratories (Erythrocyte Sedimentation Rate (ESR), White Blood Cells (WBC), Hemoglobin (Hgb), Platelets (PLTs), Alanine Aminotransferase (ALT), Total Bilirubin (T. Bili), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase (GGT), Alkaline Phosphatase (ALP) serum lipase, serum amylase and Creatinine (Cr)) are within acceptable parameters*.

    *ESR must be below 30 mm/hr; WBC >3.90 K/MM3 and <10.60 K/MM3; Hgb >/= 11.5 g/dl (women) or >/= 12.5 g/dl (men); PLTs (EDTA) 140-415 K/MM3; PLTs (Citrate) 125-325 K/MM3 ALT </= 43 U/L (women) or </= 60 U/L (men); T Bili </=1.20 mg/dl; Cr < 1.1 mg/dl (women) or < 1.4 mg/dl (men); AST 10-36 U/L (women) or 10-43 U/L (men); GGT 5--32 U/L (women) or 10-49 U/L (men); ALP 30-115 U/L (women) or 43-115 U/L (men); lipase 13-60 U/L; amylase (Total) 35-121 U/L, for subjects to qualify for randomization and vaccination.

  11. Women of childbearing potential* must use an acceptable contraception method** from at least 30 days before the first study vaccination until 60 days after the second study vaccination.

    *Not sterilized via bilateral oophorectomy, tubal ligation/ salpingectomy, hysterectomy, or successful Essure(R) placement (permanent, non-surgical, non-hormonal sterilization) with documented radiological confirmation test at least 90 days after the procedure, and still menstruating or <1 year has passed since the last menses if menopausal.

    • Includes non-male sexual relationships, full abstinence from sexual intercourse with a male partner, monogamous relationship with vasectomized partner who has been vasectomized for 180 days or more and shown to be azoospermic prior to the subject receiving the study vaccination, barrier methods such as condoms or diaphragms/cervical cap with spermicide, effective intrauterine devices, NuvaRing(R), and licensed hormonal methods such as implants, injectables or oral contraceptives ("the pill").
  12. Women of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to the first study vaccination.
  13. For a woman with potential to become pregnant, she understands that in the event of pregnancy during the study she will be approached to enroll in the Sanofi Pregnancy Registry.
  14. Must agree to have residual specimens (i.e. residual/excess of per protocol specifications).

Exclusion Criteria:

  1. Have an acute illness*, as determined by the site Principal Investigator (PI) or appropriate sub-investigator, within 72 hours prior to study vaccination.

    *An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the site PI or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol.

  2. Have any medical disease or condition that, in the opinion of the site PI or appropriate sub-investigator, is a contraindication to study participation*.

    *Including acute, subacute, intermittent or chronic medical disease or condition that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this trial.

  3. Have immunosuppression as a result of an underlying illness or treatment, a recent history or current use of immunosuppressive or immunomodulating disease therapy.
  4. Use of anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior to study vaccination.
  5. Have known active or recently active (12 months) neoplastic disease or a history of any hematologic malignancy. Non-melanoma, treated, skin cancers are permitted.
  6. Have known human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection.
  7. Have known hypersensitivity or allergy to eggs, egg or chicken protein, squalene-based adjuvants, or other components of the study vaccine.
  8. Have a history of severe reactions following previous immunization with licensed or unlicensed influenza vaccines.
  9. Have a history of Guillain-Barré Syndrome (GBS).
  10. Have a history of convulsions or encephalomyelitis within 90 days prior to study vaccination.
  11. Have a history of Potentially Immune-Mediated Medical Conditions (PIMMCs).
  12. Have a history of alcohol or drug abuse within 5 years prior to study vaccination.

  13. Have any diagnosis, current or past, of schizophrenia, bipolar disease or other psychiatric diagnosis that may interfere* with subject compliance or safety evaluations.

    *As determined by the site PI or appropriate sub-investigator.

  14. Have been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others within 5 years prior to study vaccination.
  15. Have taken oral or parenteral (including intra-articular) corticosteroids of any dose within 30 days prior to study vaccination.

  16. Have taken high-dose inhaled corticosteroids* within 30 days prior to study vaccination.

    *High-dose defined as per age as using inhaled high-dose per reference chart in the National Heart, Lung and Blood Institute Guidelines for the Diagnosis and Management of Asthma (EPR-3) or other lists published in UPTODATE.

  17. Received or plan to receive a licensed, live vaccine (excluding all licensed, seasonal LAIVs) within 30 days before or after the study vaccination.
  18. Received or plan to receive a licensed, inactivated vaccine (excluding all licensed, seasonal IIVs) within 14 days before or after each study vaccination.
  19. Have received any 2018/2019 seasonal influenza vaccine within the 6 months prior to enrollment.
  20. Plans to receive any 2019/2020 seasonal influenza vaccine within approximately 90 days of receipt of the first study vaccination.
  21. Have a known history of documented influenza infection within the past 6 months.
  22. Received immunoglobulin or other blood products (except Rho D immunoglobulin) within 90 days prior to study vaccination.

  23. Received an experimental agent* within 30 days prior to the study vaccination or expect to receive another experimental agent* during the trial-reporting period*.

    *Including vaccine, drug, biologic, device, blood product, or medication.

    **Other than from participation in this trial.

    ***Approximately 12 months after the first study vaccination.

  24. Are participating or plan to participate in another clinical trial with an interventional agent* that will be received during the trial-reporting period**.

    *Including licensed or unlicensed vaccine, drug, biologic, device, blood product, or medication.

    **Approximately 12 months after the first study vaccination.

  25. Female subjects who are breastfeeding or plan to breastfeed from the time of the first study vaccination through 30 days after the last study vaccination.
  26. Plan to travel outside the US (continental US, Hawaii and Alaska) from the time of study vaccination through approximately 90 days after the first study vaccination.
  27. Planning to donate blood within 4 months following first vaccination.

Exclusion Criteria for Second Study Vaccination:

All study participants will be expected to receive the second study vaccination except under the circumstances listed below. The second study vaccination will not be administered to a subject if any of the following criteria are met:

  • Meets the contraindication on the package insert to receipt of licensed influenza vaccine.
  • As deemed necessary by the site principal investigator or appropriate sub-investigator for noncompliance or other reasons.
  • Subject refusal of further study vaccination.
  • Withdrawal of consent.
  • Subject is lost to follow-up.
  • Termination of this trial.
  • New information becomes available that makes further participation unsafe.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03945825
Other Study ID Numbers  ICMJE 18-0011
HHSN272201300015I
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date February 19, 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

治疗医院

新药特效药

治疗案例

前沿医讯