A Study of Rilzabrutinib in Adult Patients With Immune Thrombocytopenia (ITP)
- Conditions
- Immune ThrombocytopeniaImmune Thrombocytopenic Purpura
- Interventions
- Registration Number
- NCT03395210
- Lead Sponsor
- Principia Biopharma, a Sanofi Company
- 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.
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 81
- Male or female patients, aged 18 to 80 years old
- Immune-related ITP (both primary and secondary)
- Pregnant or lactating women
- Current drug or alcohol abuse
- History of solid organ transplant
- Positive screening for HIV, hepatitis B, or hepatitis C
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Rilzabrutinib (PRN1008) Daily Rilzabrutinib 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
- Primary Outcome Measures
Name Time Method Part A and B: Incidence of Treatment Emergent Adverse Events (Safety Outcome Measure) 24 weeks of treatment, long term extension and 4 weeks of follow up post last dose] Including clinically significant changes in physical examination, laboratory tests, electrocardiogram (ECG), and vital signs.
Part A: Consecutive Increased Platelet Counts (Efficacy Outcome Measure) 24 weeks 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.
Part B: Sustained Increase in Platelet Counts (Efficacy Outcome Measure) 24 weeks 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.
- Secondary Outcome Measures
Name Time Method 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) 24 weeks Part A: Proportion of patients with 4 out of the final 8 platelet counts ≥ 50,000/μL across all dose levels 24 weeks 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 24 weeks Part A: Number of weeks with platelet counts ≥50,000/μL across all dose levels. 24 weeks 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 24 weeks Part A and B: Plasma PK parameters of rilzabrutinib Up to long term extension and 4 weeks of follow up post last dose Part A: Percent of weeks with platelet counts ≥ 50,000/μL by dose level and overall 24 weeks 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) 24 weeks Part B: Proportion of patients receiving rescue medication 24 weeks Part B: Change from baseline in ITP Bleeding Assessment Tool (ITP-BAT) 24 weeks Part A: Proportion of patients receiving rescue medication at each dosing level and overall 24 weeks Part A: Number of weeks with platelet counts ≥30,000/μL across all dose levels 24 weeks Part A: Time to first platelet count ≥50,000/μL across all dose levels 24 weeks Part A: Proportion of patients with a Grade 2 or higher bleeding event at each dosing level and overall 24 weeks Part A: Bleeding scale (ITP-BAT scale) at the end of treatment period for each dosing level 24 weeks
Trial Locations
- Locations (31)
Beth Israel Deaconess Medical Center Site Number : 1099
🇺🇸Boston, Massachusetts, United States
Investigational Site Number : 1162
🇨🇦Montreal, Quebec, Canada
Investigational Site Number : 103
🇦🇺Perth, Western Australia, Australia
Investigational Site Number : 102
🇦🇺Woolloongabba, Queensland, Australia
Massachusetts General Hospital Cancer Center Site Number : 1092
🇺🇸Boston, Massachusetts, United States
New York Presbyterian Hospital/Weill Cornell Medical Center Site Number : 1097
🇺🇸New York, New York, United States
RCCA MC LLC Site Number : 1091
🇺🇸Bethesda, Maryland, United States
Investigational Site Number : 104
🇦🇺Sydney, New South Wales, Australia
Investigational Site Number : 433
🇨🇿Hradec Kralove, Czechia
Investigational Site Number : 431
🇨🇿Brno, Czechia
Investigational Site Number : 542
🇳🇴Bergen, Norway
Investigational Site Number : 983
🇬🇧London, London, City Of, United Kingdom
Investigational Site Number : 432
🇨🇿Praha 2, Czechia
Investigational Site Number : 728
🇳🇱s-Gravenhage, Netherlands
Investigational Site Number : 980
🇬🇧London, London, City Of, United Kingdom
Investigational Site Number : 981
🇬🇧Leicester, Leicestershire, United Kingdom
Investigational Site Number : 984
🇬🇧Birmingham, United Kingdom
Pitt County Memorial Hospital Site Number : 1095
🇺🇸Greenville, North Carolina, United States
Seattle Cancer Care Alliance Site Number : 1098
🇺🇸Seattle, Washington, United States
Bleeding and Clotting Disorders Institute Site Number : 1087
🇺🇸Peoria, Illinois, United States
Investigational Site Number : 434
🇨🇿Ostrava - Poruba, Czechia
Investigational Site Number : 106
🇦🇺Parkville, Victoria, Australia
Investigational Site Number : 213
🇧🇬Pleven, Bulgaria
Investigational Site Number : 541
🇳🇴Gralum, Norway
Investigational Site Number : 1161
🇨🇦Toronto, Ontario, Canada
Investigational Site Number : 211
🇧🇬Varna, Bulgaria
Investigational Site Number : 214
🇧🇬Sofia, Bulgaria
Mid Michigan Medical Center Site Number : 1086
🇺🇸Midland, Michigan, United States
Investigational Site Number : 727
🇳🇱Rotterdam, Netherlands
Investigational Site Number : 105
🇦🇺Canberra, Australian Capital Territory, Australia
Investigational Site Number : 101
🇦🇺Clayton, Victoria, Australia