A Study of PRN1008 in Adult Patients With Immune Thrombocytopenia (ITP)

Brief Summary
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.
Brief Title
A Study of Rilzabrutinib in Adult Patients With Immune Thrombocytopenia (ITP)
Detailed Description
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.
Completion Date
Completion Date Type
Estimated
Conditions
Immune Thrombocytopenia
Immune Thrombocytopenic Purpura
Eligibility Criteria
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
Inclusion Criteria
Inclusion Criteria:

* Male or female patients, aged 18 to 80 years old
* Immune-related ITP (both primary and secondary)

Gender
All
Gender Based
false
Keywords
ITP
Healthy Volunteers
No
Last Update Submit Date
Maximum Age
80 Years
Minimum Age
18 Years
NCT Id
NCT03395210
Org Class
Industry
Org Full Name
Sanofi
Org Study Id
DFI17124
Overall Status
Active, not recruiting
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
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
Primary Outcomes
Outcome Description
Including clinically significant changes in physical examination, laboratory tests, electrocardiogram (ECG), and vital signs.
Outcome Measure
Part A and B: Incidence of Treatment Emergent Adverse Events (Safety Outcome Measure)
Outcome Time Frame
24 weeks of treatment, long term extension and 4 weeks of follow up post last dose]
Outcome Description
Proportion of patients able to achieve 2 or more consecutive platelet counts, separated by at least 5 days, of ≥50,000/μL AND an increase of platelet count of ≥20,000/μL from baseline, by dose level, without use of rescue medication in the 4 weeks prior to the latest elevated platelet count.
Outcome Measure
Part A: Consecutive Increased Platelet Counts (Efficacy Outcome Measure)
Outcome Time Frame
24 weeks
Outcome Description
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 after 10 weeks of active treatment.
Outcome Measure
Part B: Sustained Increase in Platelet Counts (Efficacy Outcome Measure)
Outcome Time Frame
24 weeks
Secondary Ids
Secondary Id
PRN1008-010
Secondary Id
U1111-1260-4044
Secondary Id
2023-509397-39
Secondary Outcomes
Outcome Time Frame
24 weeks
Outcome Measure
Part A: Percent of weeks with platelet counts ≥ 50,000/μL by dose level and overall
Outcome Time Frame
24 weeks
Outcome Measure
Part A: Proportion of patients with 4 out of the final 8 platelet counts ≥ 50,000/μL across all dose levels
Outcome Time Frame
24 weeks
Outcome Measure
Part A: Change from baseline to the average of the post Day 1 platelet counts by dose level and overall for patients who had >4 weeks of study drug on that given dose level
Outcome Time Frame
24 weeks
Outcome Measure
Part A: Number of weeks with platelet counts ≥50,000/μL across all dose levels.
Outcome Time Frame
24 weeks
Outcome Measure
Part A: Number of weeks with platelet counts ≥30,000/μL across all dose levels
Outcome Time Frame
24 weeks
Outcome Measure
Part A: Time to first platelet count ≥50,000/μL across all dose levels
Outcome Time Frame
24 weeks
Outcome Measure
Part B: Number of weeks with platelet count ≥50,000/μL OR ≥30,000/μL and doubling the baseline in the absence of rescue therapy (platelet counts will be censored for 4 weeks after the use of rescue medication, if given)
Outcome Time Frame
24 weeks
Outcome Measure
Part B: Proportion of all treated patients able to achieve≥2 consecutive platelet counts, separated by≥5days, of≥50,000/μL AND increase of platelet count of≥20,000/μL from baseline w/o rescue medication use in 4wks prior to latest elevated platelet count
Outcome Time Frame
24 weeks
Outcome Measure
Part B: Number of weeks with platelet counts ≥30,000/μL and doubling from baseline over the 24-week treatment period (platelet counts will be censored for 4 weeks after the use of rescue medication, if given)
Outcome Time Frame
24 weeks
Outcome Measure
Part B: Proportion of patients receiving rescue medication
Outcome Time Frame
24 weeks
Outcome Measure
Part B: Change from baseline in ITP Bleeding Assessment Tool (ITP-BAT)
Outcome Time Frame
24 weeks
Outcome Measure
Part A: Proportion of patients receiving rescue medication at each dosing level and overall
Outcome Time Frame
24 weeks
Outcome Measure
Part A: Proportion of patients with a Grade 2 or higher bleeding event at each dosing level and overall
Outcome Time Frame
24 weeks
Outcome Measure
Part A: Bleeding scale (ITP-BAT scale) at the end of treatment period for each dosing level
Outcome Time Frame
Up to long term extension and 4 weeks of follow up post last dose
Outcome Measure
Part A and B: Plasma PK parameters of rilzabrutinib
Start Date
Start Date Type
Actual
Status Verified Date
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
80
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Irina Murakhovskaya
Investigator Email
imurakho@montefiore.org
Investigator Phone
IMURAKHO