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

• ClinicalTrials.gov Identifier: NCT03951623
• Recruitment Status: Unknown
• First Posted: May 15, 2019
• Last Update Posted: October 22, 2020
• Sponsor: Hutchison Medipharma Limited
• Information provided by (Responsible Party): Hutchmed ( Hutchison Medipharma Limited )

Tracking Information

• First Submitted Date: May 14, 2019
• First Posted Date: May 15, 2019
• Last Update Posted Date: October 22, 2020
• Actual Study Start Date: August 12, 2019
• Estimated Primary Completion Date: December 31, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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

Current Secondary Outcome Measures (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 (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: The Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of HMPL-523 in Immune Thrombocytopenia Patients
• 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
• 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: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Immune Thrombocytopenia (ITP)

Intervention

• 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

• 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

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: May 14, 2019): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2021
• Estimated Primary Completion Date: December 31, 2021 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03951623
• Other Study ID Numbers: 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

• Plan to Share IPD: No

• Current Responsible Party: Hutchmed ( Hutchison Medipharma Limited )
• Original Responsible Party: Same as current
• Current Study Sponsor: Hutchison Medipharma Limited
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Hongyan Yin; Hutchison MediPharma

• PRS Account: Hutchmed
• Verification Date: September 2020