A Study of Rilzabrutinib in Adult Patients With Immune Thrombocytopenia (ITP)

Study Overview
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Brief Summary
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This is a 2 part (Part A and B) adaptive, open-label, dose-finding study of PRN1008 in patients with ITP who are refractory or relapsed with no available and approved therapeutic options, with a platelet count <30,000/μL on two counts no sooner than 7 days apart in the 15 days before treatment begins. The dose-finding portion of the study has been completed. Part B treatment dose is 400 mg twice daily.

Detailed Description
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This is a 2 part (Part A and B) adaptive, open-label, dose-finding study of PRN1008 in approximately 60 patients in Part A and approximately 25 patients in Part B. Part A enrolls patients with ITP who are refractory or relapsed with no available and approved therapeutic options. Eligible patients have a platelet count <30,000/μL on two counts no sooner than 7 days apart in the 15 days before treatment begins. The active treatment period is 24 weeks and the post-treatment follow-up period is 4 weeks. In the dose-finding part of the study, each patient enrolled in the study is allowed to up-titrate their dose after 28 days of PRN1008 therapy, if they do not experience a platelet response or a dose-limiting toxicity (DLT) at the last dose level. Patients who respond to PRN1008 per protocol may enter a long term-extension. Part B of the study will include approximately 25 patients with ITP who have relapsed or have an insufficient response to prior therapies. Eligible patients will have a platelet count <30,000/µL on two occasions no less than 7 days apart, within 15 days before treatment begins and a platelet count of ≤35,000/µL on Study Day 1 (SD1). The study consists of a 28-day screening period, 24-week active treatment period, and a long-term extension. After the last dose of PRN1008 there will be a 4-week safety follow-up period.

Official Title
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An Adaptive, Open-Label, Dose-Finding, Phase 1/2 Study Investigating the Safety, Pharmacokinetics, and Clinical Activity of PRN1008, an Oral BTK Inhibitor, in Patients With Relapsed Immune Thrombocytopenia

Conditions
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Immune Thrombocytopenia, Immune Thrombocytopenic Purpura

Intervention / Treatment
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* Drug: PRN1008


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients, aged 18 to 80 years old Immune-related ITP (both primary and secondary) Exclusion Criteria: Pregnant or lactating women Current drug or alcohol abuse History of solid organ transplant Positive screening for HIV, hepatitis B, or hepatitis C

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
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRN1008 Daily<br>Part A approximately 60 patients: Up to 24 weeks open-label treatment with PRN1008 400mg BID; safety and dose evaluation. Patients who respond to PRN1008 per protocol may enter a long-term extension. Part B approximately 25 patients: Up to 24 weeks open-label treatment with PRN1008 400mg BID; safety and dose evaluation. Patients who respond to PRN1008 per protocol may enter a long-term extension | Drug: PRN1008<br>* BTK inhibitor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A and B: Incidence of Treatment Emergent Adverse Events (Safety Outcome Measure) | The incidence, severity and relationship of TEAEs during the treatment period and at the 4-week follow-up from last dose received. | 24 weeks of treatment, long term extension and 4 weeks of follow up post last dose] | 
| Part A: Consecutive Increased Platelet Counts (Efficacy Outcome Measure) | Proportion of subjects able to achieve two or more consecutive platelet counts of ≥ 50,000/μL AND an increase of platelet count of ≥20,000/μL from baseline, without the use of rescue medication | 24 weeks | 
| Part B: Sustained Increase in Platelet Counts (Efficacy Outcome Measure) | Proportion of patients able to achieve platelet counts ≥50,000/μL on at least 8 out of the last 12 weeks of the 24-week treatment period without the use of rescue medication | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ITP