A Study to Evaluate the Efficacy and Safety of Orelabrutinib in Adult Patients With Immune Thrombocytopenia

Study Overview
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Brief Summary
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The study is designed to be a randomized, open, multi-center, phase IIa/IIb seamless adaptive trial. Phase IIa: The study consists of a screening period, a core treatment period, an open label extension period, and a safety follow-up period Phase IIb: At present, a preliminary exploratory study (i.e., phase IIa study) will be conducted first. The design of the phase IIb study (including the selection of populations) will be clarified after a relatively clear understanding of the therapeutic effect, value, risks and benefits of the BTK inhibitor for ITP is obtained.

Official Title
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A Randomized, Multi-center, Adaptive Phase IIa/IIb Study to Evaluate the Efficacy and Safety of Orelabrutinib in Adult Patients With Persistent or Chronic Primary Immune Thrombocytopenia

Conditions
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Primary Immune Thrombocytopenia

Intervention / Treatment
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* Drug: Orelabrutinib( lower dose)
* Drug: Orelabrutinib( higher dose)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects have had a detailed understanding of the nature, significance, possible benefits, possible inconveniences, and potential risks of the trial, understood the study procedures, and voluntarily signed a written ICF before the study. Males or females aged from 18 to 80 years (including the marginal values). With a body weight of ≥ 35 kg at screening. Diagnostic criteria:the diagnosis of persistent (3-12 months) or chronic (≥ 12 months) ITP is met Patients who have failed at least 1 prior first-line standard therapy for ITP, or who have failed to tolerate a standard therapy. Women of childbearing potential must take a complementary barrier method of contraception in combination with a highly effective method of contraception at screening, throughout the trial, and within 90 days after the last dose of the investigational drug. The mean of two platelet counts is less than 30 × 109/L and no platelet count is greater than 35 × 109/L during the screening visit and/or before the first dose. Exclusion Criteria: Severe hemorrhage occurred within 4 weeks prior to screening. Subjects suffer from severe ITP at screening Subjects have other diseases which mention in protocol Subjects develop intracranial hemorrhage within 6 months prior to screening. Active and uncontrollable infection Subjects have a history of coagulopathy other than ITP Subjects with a history of malignancies. History of major organ transplantation or hematopoietic stem cell/bone marrow transplantation. Subjects with a known history of hypersensitivity to the investigational drug as described in the Protocol, or any ingredients. Subjects with a Medication history and surgical history which mention in protocol Subjects do not meet the criterion of the laboratory test in protocol NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lower Dose<br>Orelabrutinib is a white, round, uncoated tablet | Drug: Orelabrutinib( lower dose)<br>* Orelabrutinib is a white, round, uncoated tablet, will be taken lower dose QD by patients with persistent or chronic primary immune thrombocytopenia<br>|
| Experimental: Higher Dose<br>Orelabrutinib is a white, round, uncoated tablet | Drug: Orelabrutinib( higher dose)<br>* Orelabrutinib is a white, round, uncoated tablet, will be taken higher dose QD by patients with persistent or chronic primary immune thrombocytopenia<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with the platelet count of ≥ 50 × 109/L after 12 weeks of treatment |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects who achieve a complete response (CR) over treatment time. CR is defined as a post-treatment platelet count of ≥100 × 109/L |  | 25 weeks | 
| Occurrence of treatment emergent adverse events (TEAE) and treatment-related adverse events (TRAE) were evaluated according to severity |  | 25 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Persistent or chronic