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出境医 / 临床实验 / The Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of HMPL-523 in Immune Thrombocytopenia Patients

The Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of HMPL-523 in Immune Thrombocytopenia Patients

Study Description
Brief Summary:
This is a randomized, double blinded, placebo-controlled phase Ib clinical trial in adult patients with immune thrombocytopenia. Cross-over treatment will be allowed during the study.

Condition or disease Intervention/treatment Phase
Immune Thrombocytopenia (ITP) Drug: HMPL-523 Drug: Placebo Phase 1

Detailed Description:
Approximate 51 to 60 patients will be enrolled in dose escalation (3 cohorts, 8-20 subjects each with the ratio of 3:1 vs Placebo) .
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of HMPL-523, a Syk Inhibitor in Adult Patients of Immune Thrombocytopenia: a Randomized, Double Blinded, Placebo Controlled Phase Ib Study
Actual Study Start Date : August 12, 2019
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021
Arms and Interventions
Arm Intervention/treatment
Active Comparator: treatment arm
Eligible subjects will be treated with planned dose of 100 mg, 200 mg and 300 mg HMPL-523 once daily for 8 weeks and 16 weeks open-label treatment.
Drug: HMPL-523
HMPL-523 will be oral administrated once daily for 8 weeks and 16 weeks open-label treatment.

Placebo Comparator: placebo arm
Eligible subjects will be treated with HMPL-523 matching placebo once daily for 8 weeks and 16 weeks open-label treatment.
Drug: HMPL-523
HMPL-523 will be oral administrated once daily for 8 weeks and 16 weeks open-label treatment.

Drug: Placebo
HMPL-523 matching placebo will be oral administrated once daily for 8 weeks and 16 weeks open-label treatment.

Outcome Measures
Primary Outcome Measures :
  1. Number of Participants with any Adverse Event [ Time Frame: From first dose to within 28 days after the last dose ]
    Adverse Events evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0


Secondary Outcome Measures :
  1. Maximum plasma concentration (Cmax) [ Time Frame: Day 15, 16, 29, 43 and 47 ]
    Maximum plasma concentration (Cmax)

  2. Area under the concentration-time curve in a selected time interval (AUC0-t) [ Time Frame: Day 15, 16, 29, 43 and 47 ]
    Area under the concentration-time curve in a selected time interval (AUC0-t)

  3. Rate of Clinical Remission [ Time Frame: Day 1 to 8 weeks treatment ]
    Rate of Clinical Remission was defined as the proportion of patients with two consecutive visits in the first 8 weeks (including the 8th week) during the medication period, platelet count ≥30×10^9/L, and a 2-fold increase from baseline (no emergency treatment during the period)


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed informed consent form
  2. 18~75 years old male of female
  3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  4. Diagnosed immune thrombocytopenia before randomization with platelet decrease for more than 6 months.
  5. Patients with refractory or relapsed ITP who have been treated with 1st line anti-ITP regimen or have experienced splenectomy.
  6. Relative stable disease with World Health Organization (WHO) bleeding score of 0-1 and no rescue treatment needed within 2 weeks based on investigator's judgment.
  7. Laboratory tests meet the following conditions:

    • During screening stage, twice PLT<30x10^9/L(exceed 24 hours)
    • Hb≥90g/L(if iron-deficiency anemia,Hb>80g/L),WBC>2.5x10^9/L, NEU>1.8x10^9/L
    • Crea≤1.5xULN and CCR≥50mL/min
    • TBIL、ALT、AST≤1.5xULN
    • Amylase、lipase<ULN
    • INR、APTT<20%xULN

Exclusion Criteria:

  1. Patients with secondary thrombocytopenia or patients have other auto immune diseases who need long term steroids or immunosuppressants treatment.
  2. Patients with Myelofibrosis, Myelodysplastic syndrome, Aplastic anemia, or other hematologic malignancies.
  3. Have splenectomy within 12 weeks before randomization
  4. Major surgery was performed within 4 weeks before randomization;Or require major elective surgery during the study period.
  5. Have malignant tumor(except basal cell carcinoma of skin and carcinoma in situ of cervix)
  6. Have previous/significant arterial/venous embolic disease
  7. History of serious cardiovascular disease, or QTc≥450 ms.
  8. Patients with resistant hypertension (Systolic blood pressure ≥140 mmHg or Diastolic blood pressure ≥90 mmHg)
  9. Has a history of severe gastrointestinal diseases, such as dysphagia, active gastric ulcer, and is unable to take oral medication or has absorption disorder
  10. HIV infection
  11. Uncontrolled, active infections
  12. Known history of clinically significant liver disease, such as hepatitis b(HBV DNA ≥2000IU/mL (or ≥1×104 copies)), hepatitis c, or cirrhosis
  13. Prior anti-ITP emergency treatment within 2 weeks before randomization.
  14. Prior anti-ITP treatment within 4 weeks before randomization except for stable dose steroids, including but not limited to Thrombopoietin, thrombopoietin receptor agonist, azathioprine, cyclosporine A and mycophenolate mofetil.
  15. Any condition requiring anti-coagulant therapy or the regular use of any medication having effluence to Platelet function.
  16. Exposure to Rituximab 14 weeks prior to randomization.
  17. Treament with Chinese medicine within 1 week before randomization.
  18. Use of strong cytochrome P450 isoform 3A inhibitors and inducers and drugs metabolized by cytochrome P450 isoform 3A, cytochrome P450 isoform 2B6, and cytochrome P450 isoform 1A2, and are identified as narrow therapeutic drugs within 14 days or 5 half-lives, whichever is longer, prior to initiation of study treatment.
  19. Prior treatment with any spleen tyrosine kinase (SYK) inhibitors (eg, fostamatinib)
  20. Allergic to study drug active ingredient or excipient
  21. Subjects who have participated in clinical studies of drugs or invasive medical devices within 4 week before randomization
  22. Subjects have severe psychological or mental abnormalities
  23. Alcoholic or drug abuser
  24. Female subjects during pregnancy and lactation
  25. The investigator considered that the subjects were not suitable to participate in the study
Contacts and Locations

Contacts
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Contact: jiayi Mai 086-021-20673063 Jiayim@hmplglobal.com

Locations
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China, Tianjin
Blood diseases hospital, Chinese academy of medical university Recruiting
Tianjin, Tianjin, China, 300000
Contact: Renchi Yang       rcyang65@163.com   
Sponsors and Collaborators
Hutchison Medipharma Limited
Investigators
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Study Director: Hongyan Yin Hutchison MediPharma
Tracking Information
First Submitted Date  ICMJE May 14, 2019
First Posted Date  ICMJE May 15, 2019
Last Update Posted Date October 22, 2020
Actual Study Start Date  ICMJE August 12, 2019
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 27, 2019)
Number of Participants with any Adverse Event [ Time Frame: From first dose to within 28 days after the last dose ]
Adverse Events evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Original Primary Outcome Measures  ICMJE
 (submitted: May 14, 2019)
Adverse Events [ Time Frame: From first dose to within 28 days after the last dose ]
Adverse Events evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 20, 2020)
  • Maximum plasma concentration (Cmax) [ Time Frame: Day 15, 16, 29, 43 and 47 ]
    Maximum plasma concentration (Cmax)
  • Area under the concentration-time curve in a selected time interval (AUC0-t) [ Time Frame: Day 15, 16, 29, 43 and 47 ]
    Area under the concentration-time curve in a selected time interval (AUC0-t)
  • Rate of Clinical Remission [ Time Frame: Day 1 to 8 weeks treatment ]
    Rate of Clinical Remission was defined as the proportion of patients with two consecutive visits in the first 8 weeks (including the 8th week) during the medication period, platelet count ≥30×10^9/L, and a 2-fold increase from baseline (no emergency treatment during the period)
Original Secondary Outcome Measures  ICMJE
 (submitted: May 14, 2019)
  • Maximum plasma concentration (Cmax) [ Time Frame: Day 15, 16, 29, 43 and 47 in dose esclation phase and Day 15, 29, 43 and 57 in dose expansion phase ]
    Maximum plasma concentration (Cmax)
  • Area under the concentration-time curve in a selected time interval (AUC0-t) [ Time Frame: Day 15, 16, 29, 43 and 47 in dose esclation phase and Day 15, 29, 43 and 57 in dose expansion phase ]
    Area under the concentration-time curve in a selected time interval (AUC0-t)
  • Clinical remission rate [ Time Frame: 1st dose to 8 weeks treatment ]
    Clinical remission rate defined as the proportion of patients who have PLT ≥30×10^9/L and increased ≥20×10^9/L vs baseline without anti-ITP emergency treatment during the study
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of HMPL-523 in Immune Thrombocytopenia Patients
Official Title  ICMJE The Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of HMPL-523, a Syk Inhibitor in Adult Patients of Immune Thrombocytopenia: a Randomized, Double Blinded, Placebo Controlled Phase Ib Study
Brief Summary This is a randomized, double blinded, placebo-controlled phase Ib clinical trial in adult patients with immune thrombocytopenia. Cross-over treatment will be allowed during the study.
Detailed Description Approximate 51 to 60 patients will be enrolled in dose escalation (3 cohorts, 8-20 subjects each with the ratio of 3:1 vs Placebo) .
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Immune Thrombocytopenia (ITP)
Intervention  ICMJE
  • Drug: HMPL-523
    HMPL-523 will be oral administrated once daily for 8 weeks and 16 weeks open-label treatment.
  • Drug: Placebo
    HMPL-523 matching placebo will be oral administrated once daily for 8 weeks and 16 weeks open-label treatment.
Study Arms  ICMJE
  • Active Comparator: treatment arm
    Eligible subjects will be treated with planned dose of 100 mg, 200 mg and 300 mg HMPL-523 once daily for 8 weeks and 16 weeks open-label treatment.
    Intervention: Drug: HMPL-523
  • Placebo Comparator: placebo arm
    Eligible subjects will be treated with HMPL-523 matching placebo once daily for 8 weeks and 16 weeks open-label treatment.
    Interventions:
    • Drug: HMPL-523
    • Drug: Placebo
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 14, 2019)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Signed informed consent form
  2. 18~75 years old male of female
  3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  4. Diagnosed immune thrombocytopenia before randomization with platelet decrease for more than 6 months.
  5. Patients with refractory or relapsed ITP who have been treated with 1st line anti-ITP regimen or have experienced splenectomy.
  6. Relative stable disease with World Health Organization (WHO) bleeding score of 0-1 and no rescue treatment needed within 2 weeks based on investigator's judgment.
  7. Laboratory tests meet the following conditions:

    • During screening stage, twice PLT<30x10^9/L(exceed 24 hours)
    • Hb≥90g/L(if iron-deficiency anemia,Hb>80g/L),WBC>2.5x10^9/L, NEU>1.8x10^9/L
    • Crea≤1.5xULN and CCR≥50mL/min
    • TBIL、ALT、AST≤1.5xULN
    • Amylase、lipase<ULN
    • INR、APTT<20%xULN

Exclusion Criteria:

  1. Patients with secondary thrombocytopenia or patients have other auto immune diseases who need long term steroids or immunosuppressants treatment.
  2. Patients with Myelofibrosis, Myelodysplastic syndrome, Aplastic anemia, or other hematologic malignancies.
  3. Have splenectomy within 12 weeks before randomization
  4. Major surgery was performed within 4 weeks before randomization;Or require major elective surgery during the study period.
  5. Have malignant tumor(except basal cell carcinoma of skin and carcinoma in situ of cervix)
  6. Have previous/significant arterial/venous embolic disease
  7. History of serious cardiovascular disease, or QTc≥450 ms.
  8. Patients with resistant hypertension (Systolic blood pressure ≥140 mmHg or Diastolic blood pressure ≥90 mmHg)
  9. Has a history of severe gastrointestinal diseases, such as dysphagia, active gastric ulcer, and is unable to take oral medication or has absorption disorder
  10. HIV infection
  11. Uncontrolled, active infections
  12. Known history of clinically significant liver disease, such as hepatitis b(HBV DNA ≥2000IU/mL (or ≥1×104 copies)), hepatitis c, or cirrhosis
  13. Prior anti-ITP emergency treatment within 2 weeks before randomization.
  14. Prior anti-ITP treatment within 4 weeks before randomization except for stable dose steroids, including but not limited to Thrombopoietin, thrombopoietin receptor agonist, azathioprine, cyclosporine A and mycophenolate mofetil.
  15. Any condition requiring anti-coagulant therapy or the regular use of any medication having effluence to Platelet function.
  16. Exposure to Rituximab 14 weeks prior to randomization.
  17. Treament with Chinese medicine within 1 week before randomization.
  18. Use of strong cytochrome P450 isoform 3A inhibitors and inducers and drugs metabolized by cytochrome P450 isoform 3A, cytochrome P450 isoform 2B6, and cytochrome P450 isoform 1A2, and are identified as narrow therapeutic drugs within 14 days or 5 half-lives, whichever is longer, prior to initiation of study treatment.
  19. Prior treatment with any spleen tyrosine kinase (SYK) inhibitors (eg, fostamatinib)
  20. Allergic to study drug active ingredient or excipient
  21. Subjects who have participated in clinical studies of drugs or invasive medical devices within 4 week before randomization
  22. Subjects have severe psychological or mental abnormalities
  23. Alcoholic or drug abuser
  24. Female subjects during pregnancy and lactation
  25. The investigator considered that the subjects were not suitable to participate in the study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: jiayi Mai 086-021-20673063 Jiayim@hmplglobal.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03951623
Other Study ID Numbers  ICMJE 2018-523-00CH1
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Hutchison Medipharma Limited
Study Sponsor  ICMJE Hutchison Medipharma Limited
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Hongyan Yin Hutchison MediPharma
PRS Account Hutchison Medipharma Limited
Verification Date September 2020

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