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
Overview
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Hutchison Medipharma Limited
- Enrollment
- 45
- Locations
- 1
- Primary Endpoint
- Number of Participants with any Adverse Event
Overview
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Signed informed consent form
- •18\~75 years old male of female
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Diagnosed immune thrombocytopenia before randomization with platelet decrease for more than 6 months.
- •Patients with refractory or relapsed ITP who have been treated with 1st line anti-ITP regimen or have experienced splenectomy.
- •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.
- •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
Exclusion Criteria
- •Patients with secondary thrombocytopenia or patients have other auto immune diseases who need long term steroids or immunosuppressants treatment.
- •Patients with Myelofibrosis, Myelodysplastic syndrome, Aplastic anemia, or other hematologic malignancies.
- •Have splenectomy within 12 weeks before randomization
- •Major surgery was performed within 4 weeks before randomization;Or require major elective surgery during the study period.
- •Have malignant tumor(except basal cell carcinoma of skin and carcinoma in situ of cervix)
- •Have previous/significant arterial/venous embolic disease
- •History of serious cardiovascular disease, or QTc≥450 ms.
- •Patients with resistant hypertension (Systolic blood pressure ≥140 mmHg or Diastolic blood pressure ≥90 mmHg)
- •Has a history of severe gastrointestinal diseases, such as dysphagia, active gastric ulcer, and is unable to take oral medication or has absorption disorder
- •HIV infection
Arms & Interventions
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: HMPL-523 (Drug)
placebo arm
Eligible subjects will be treated with HMPL-523 matching placebo once daily for 8 weeks and 16 weeks open-label treatment.
Intervention: HMPL-523 (Drug)
placebo arm
Eligible subjects will be treated with HMPL-523 matching placebo once daily for 8 weeks and 16 weeks open-label treatment.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
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 Outcomes
- Rate of Clinical Remission(Day 1 to 8 weeks treatment)
- Maximum plasma concentration (Cmax)(Day 15, 16, 29, 43 and 47)
- Area under the concentration-time curve in a selected time interval (AUC0-t)(Day 15, 16, 29, 43 and 47)