Condition or disease | Intervention/treatment | Phase |
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Rabies Rabies Immunisation | Biological: ChAd155-RG Other: Placebo Biological: Rabies Vaccine | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 50 participants |
Allocation: | Randomized |
Intervention Model: | Sequential Assignment |
Masking: | Double (Participant, Investigator) |
Primary Purpose: | Prevention |
Official Title: | A Phase 1, Dosage-Escalation Study of the Safety and Immunogenicity of a Novel Rabies Vaccine ChAd155-RG vs. the Comparator RABAVERT Vaccine in Healthy Adult Subjects |
Actual Study Start Date : | September 19, 2019 |
Estimated Primary Completion Date : | January 24, 2022 |
Estimated Study Completion Date : | January 24, 2022 |
Arm | Intervention/treatment |
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Experimental: Arm A
One dose (1 ml (5x10^10 vp)) of ChAd155-RG vaccine administered intramuscularly on Day 1, and 1 ml of matching placebo administered intramuscularly on Days 8, 15, 22. N=14 (3 sentinel, 11 non-sentinel)
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Biological: ChAd155-RG
The ChAd155-RG Vaccine consists of a replication-defective group C ChAd, ChAd155, expressing RG under the control of the CMV promoter. The RG sequence cloned into the ChAd155 vector is a medoid, a natural viral strain with the highest average percent of amino acid identity among all RG sequences annotated in the NCBI database. The selected RG (NCBI strain AGN94271) shares an average 94% percent identity to the RGs in current vaccines.
Other: Placebo 0.9% Sodium Chloride, USP injection.
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Experimental: Arm B
One dose (1 ml (1x10^11 vp)) of ChAd155-RG vaccine administered intramuscularly on Day 1, and 1 ml of matching placebo administered intramuscularly on Days 8, 15, 22. N=14 (3 sentinel, 11 non-sentinel)
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Biological: ChAd155-RG
The ChAd155-RG Vaccine consists of a replication-defective group C ChAd, ChAd155, expressing RG under the control of the CMV promoter. The RG sequence cloned into the ChAd155 vector is a medoid, a natural viral strain with the highest average percent of amino acid identity among all RG sequences annotated in the NCBI database. The selected RG (NCBI strain AGN94271) shares an average 94% percent identity to the RGs in current vaccines.
Other: Placebo 0.9% Sodium Chloride, USP injection.
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Experimental: Arm C
Two doses (1 ml (1x10^11 vp) each) of ChAd155-RG vaccine administered intramuscularly on Day 1 (first dose) and Day 15 (second dose), and 1 ml of matching placebo administered intramuscularly on Days 8 and 22. N=10
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Biological: ChAd155-RG
The ChAd155-RG Vaccine consists of a replication-defective group C ChAd, ChAd155, expressing RG under the control of the CMV promoter. The RG sequence cloned into the ChAd155 vector is a medoid, a natural viral strain with the highest average percent of amino acid identity among all RG sequences annotated in the NCBI database. The selected RG (NCBI strain AGN94271) shares an average 94% percent identity to the RGs in current vaccines.
Other: Placebo 0.9% Sodium Chloride, USP injection.
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Active Comparator: Arm D
Three doses (1 ml each) of RABAVERT vaccine administered intramuscularly on Day 1 (first dose), Day 8 (second dose), and Day 22 (third dose), and 1 ml of matching placebo administered intramuscularly on Day 15. N=12 (2 sentinel, 10 non-sentinel)
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Other: Placebo
0.9% Sodium Chloride, USP injection.
Biological: Rabies Vaccine The RABAVERT Vaccine is an inactivated, purified chick embryo cell vaccine (PCECV). It consists of lyophilized rabies virus (strain Flury LEP) that has been propagated in chicken fibroblasts, inactivated with beta-propiolactone, and concentrated and purified by centrifugation
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Ages Eligible for Study: | 18 Years to 49 Years (Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Must be in good health based on physical examination, vital signs*, medical history, safety labs**, and the investigator's clinical judgment.
*Vital signs must be within the normal ranges. If a subject has elevated systolic or diastolic blood pressure, subject may rest for 10 minutes in a quiet room and the blood pressure may be retaken.
**Safety lab normal ranges will be those used by the reference clinical lab. Protocol-specific criteria for individual subjects are listed in criteria #5.
Must have acceptable* lab values within 28 days before enrollment. *Acceptable values include:
Women of childbearing potential* must have a negative serum pregnancy test at screening and negative urine pregnancy tests within 24 hours before each vaccination.
Women of childbearing potential must use an acceptable method of contraception* from 28 days before the first vaccination until = / >60 days after the last vaccination.
*Acceptable methods of contraception include: prescription oral contraceptives, contraceptive injections, intrauterine device (IUD), implants, vaginal ring, double-barrier method, contraceptive patch, male partner who had a vasectomy at least 6 months prior to study enrollment, abstinence (defined as refraining from heterosexual intercourse during participation in this trial [from 28 days before the first vaccination until = / >60 days after the last vaccination]).
Male subjects who have not had a vasectomy* and are sexually active with a woman of childbearing potential must agree to use an acceptable method of contraception**.
*Men who have had a vasectomy must have had the procedure performed at least 6 months prior to study enrollment.
**Acceptable methods of contraception must be used from the first vaccination until = / >60 days after the last vaccination, and include: abstinence (defined as refraining from heterosexual intercourse with a female partner of childbearing potential during participation in this trial [from 28 days before the first vaccination until = / >60 days after the last vaccination]; a double-barrier method, such as condom with spermicidal foam/gel/film/cream/suppository and partner with occlusive cap (diaphragm, cervical/vault caps); if the female partner is using an acceptable method of contraception (see Inclusion Criterion #7), a single-barrier method for the male subject is acceptable.
Exclusion Criteria:
Was ever vaccinated with a licensed or investigational rabies vaccine* or was diagnosed with rabies exposure, infection, or disease.
*Includes RABAVERT and Imovax. Subject's verbal history will suffice.
Has a higher risk than the average US resident with regard to exposure to rabies, per the Rabavert package insert and rabies vaccination recommendations from the CDC*.
Has known allergy or history of anaphylaxis or other serious adverse reaction to a vaccine or vaccine products*.
*Including egg products, aminoglycosides, gelatin, sorbitol, tris (hydroxymethyl)-amino methane (THAM), or any of the constituents of the study vaccines.
Has an acute illness or temperature = / >38.0 Degrees Celsius on Day 1*.
*Subjects with fever or acute illness on the day of vaccination may be re-assessed and enrolled if healthy or only minor residual symptoms remain within 3 days.
Has history of malignancy other than squamous cell or basal cell skin cancer, unless there has been surgical excision that is considered to have achieved cure*.
*Subjects with a history of skin cancer must not be vaccinated at the previous tumor site.
Has known or suspected congenital or acquired immunodeficiency, or recent history or current use of immunosuppressive therapy*.
*Anti-cancer chemotherapy or radiation therapy within the preceding 6 months, or long-term (= / >2 weeks within the previous 3 months) systemic corticosteroid therapy (at a dosage of = / >0.5 mg/kg/day). Intranasal or topical prednisone (or equivalent) are allowed.
Has history of diabetes mellitus type 1 or type 2, including cases controlled with diet alone.
*Note: history of isolated gestational diabetes is not an exclusion criterion.
Has history of hypertension, even if medically controlled.
*Note: Vital signs must be normal by protocol toxicity grading scale. In the event of an abnormal heart rate or blood pressure due to physiological variation or activity, the subject may rest for 10 minutes in a quiet room, and then blood pressure and/or heart rate re-measured. Repeated vital signs may be used to determine eligibility.
Received live attenuated vaccines from 30 days before first vaccination until 30 days after final vaccination*.
*Not including licensed or authorized COVID-19 vaccines.
Received killed or inactivated vaccines from 14 days before first vaccination until 30 days after final vaccination*.
*Not including licensed COVID-19 vaccines
Received experimental therapeutic agents within 3 months before first vaccination or plans to receive any experimental therapeutic agents during this trial*.
*That that in the opinion of the investigator would interfere with safety or immunogenicity assessments.
Is currently participating or plans to participate in another clinical study which would involve receipt of the following:*
* An investigational product, blood drawing, or an invasive medical procedure that would require administration of anesthetics, intravenous (IV) dyes, or removal of tissue during this trial and, in the opinion of the investigator, would interfere with safety or immunogenicity assessments.
-Includes endoscopy, bronchoscopy, and administration of IV contrast.
Is a site employee* or staff who are paid entirely or partially by/through the OCRR contract for this trial, or staff who are supervised by the Principal Investigator (PI) or sub-investigators.
*Including the PI, sub-investigators listed on Form FDA 1572 or Investigator of Record Form.
Contact: Varun Phadke | 14047121585 | vphadke@emory.edu |
United States, Georgia | |
Emory Vaccine Center - The Hope Clinic | Recruiting |
Decatur, Georgia, United States, 30030-1705 |
Tracking Information | |||||||
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First Submitted Date ICMJE | July 11, 2019 | ||||||
First Posted Date ICMJE | July 15, 2019 | ||||||
Last Update Posted Date | June 4, 2021 | ||||||
Actual Study Start Date ICMJE | September 19, 2019 | ||||||
Estimated Primary Completion Date | January 24, 2022 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE | Same as current | ||||||
Change History | |||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||
Descriptive Information | |||||||
Brief Title ICMJE | Dosage-Escalation Study of the Safety and Immunogenicity of a Novel Rabies Vaccine ChAd155-RG vs. the Comparator RABAVERT Vaccine in Healthy Adult Subjects | ||||||
Official Title ICMJE | A Phase 1, Dosage-Escalation Study of the Safety and Immunogenicity of a Novel Rabies Vaccine ChAd155-RG vs. the Comparator RABAVERT Vaccine in Healthy Adult Subjects | ||||||
Brief Summary | This is a single-center, observer-blinded, dosage-escalation trial to evaluate the safety, tolerability, reactogenicity, and immunogenicity of ChAd155-RG compared with RABAVERT in rabies virus-naïve healthy male and non-pregnant female adult subjects ages 18-49. There are 4 dose groups: Group A will receive ChAd155-RG at the lower dosage (5x1010vp) on Day 1, then placebo injections on Days 8, 15, and 22; Group B will receive ChAd155-RG at the higher dosage (1x1011vp) on Day 1, then placebo injections on Days 8, 15, and 22; Group C will receive ChAd155-RG at the higher dosage (1x1011vp) on Days 1 and 15, and placebo injections on Days 8 and 22; Group D will receive RABAVERT at the standard dose (1 mL) on Days 1, 8, and 22, and a placebo injection on Day 15. Since this is a dosage-escalation study, sentinel subjects will be used at each dosage level before non-sentinel subjects will be enrolled. The study will be conducted at Emory University Vaccine and Treatment Evaluation Unit (VTEU). This trial is expected to take approximately 48 months to complete. The duration of each subject's participation is approximately 13 months, from recruitment through the last study visit. The primary objectives of this study are: 1) Assessment of the safety, tolerability, and reactogenicity of one dose of ChAd155-RG at 5x1010vp per dose, or one or two doses of ChAd155-RG at 1x1011vp per dose; 2) Comparison of the safety, tolerability, and reactogenicity of one or two doses of ChAd155-RG, with three doses of RABAVERT. | ||||||
Detailed Description | This is a single-center, observer-blinded, Phase 1, dosage-escalation trial to evaluate the safety, tolerability, reactogenicity, and immunogenicity of ChAd155-RG compared with RABAVERT in rabies virus-naïve healthy male and non-pregnant female adult subjects ages 18-49. Subjects who have never received a licensed or investigational rabies virus vaccine, or an Ad-based investigational vaccine, and who have never been exposed to a rabid animal will be eligible for enrollment. There are 4 dose groups: Group A will receive ChAd155-RG at the lower dosage (5x1010vp) on Day 1, then placebo injections on Days 8, 15, and 22; Group B will receive ChAd155-RG at the higher dosage (1x1011vp) on Day 1, then placebo injections on Days 8, 15, and 22; Group C will receive ChAd155-RG at the higher dosage (1x1011vp) on Days 1 and 15, and placebo injections on Days 8 and 22; Group D will receive RABAVERT at the standard dose (1 mL) on Days 1, 8, and 22, and a placebo injection on Day 15. Since this is a dosage-escalation study, sentinel subjects will be used at each dosage level before non-sentinel subjects will be enrolled. The SMC will review the available safety, reactogenicity, AE, and lab data of all the sentinel subjects, and will decide if the remaining non-sentinel subjects should be enrolled. The study will be conducted at Emory University Vaccine and Treatment Evaluation Unit (VTEU). This trial is expected to take approximately 48 months to complete. The duration of each subject's participation is approximately 13 months, from recruitment through the last study visit. The primary objectives of this study are: 1) Assessment of the safety, tolerability, and reactogenicity of one dose of ChAd155-RG at 5x1010vp per dose, or one or two doses of ChAd155-RG at 1x1011vp per dose; 2) Comparison of the safety, tolerability, and reactogenicity of one or two doses of ChAd155-RG, with three doses of RABAVERT. The secondary objective is to assess the serum rabies VNA levels by a standard, WHO-approved, RFFIT, as assessed by immune response kinetics (through approximately 12 months after first dose of vaccine), seroconversion rates, and peak GMT in each treatment arm. | ||||||
Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 1 | ||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Sequential Assignment Masking: Double (Participant, Investigator) Primary Purpose: Prevention |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||
Recruitment Status ICMJE | Recruiting | ||||||
Estimated Enrollment ICMJE |
50 | ||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||
Estimated Study Completion Date ICMJE | January 24, 2022 | ||||||
Estimated Primary Completion Date | January 24, 2022 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years to 49 Years (Adult) | ||||||
Accepts Healthy Volunteers ICMJE | Yes | ||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | United States | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT04019444 | ||||||
Other Study ID Numbers ICMJE | 17-0089 HHSN272201300018I |
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Has Data Monitoring Committee | Not Provided | ||||||
U.S. FDA-regulated Product |
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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 | March 2021 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |