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

Immune Thrombocytopenia Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03395210
• Other study ID #: DFI17124
• Secondary ID: PRN1008-010U1111
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 22, 2018
• Est. completion date: December 31, 2025

Study information

• Verified date: May 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 81
• Est. completion date: December 31, 2025
• Est. primary completion date: January 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Immune Thrombocytopenia
• Immune Thrombocytopenic Purpura
• Purpura
• Purpura, Thrombocytopenic
• Purpura, Thrombocytopenic, Idiopathic
• Thrombocytopenia

Intervention

Drug:
• Rilzabrutinib
BTK inhibitor

Locations

Country	Name	City	State
Australia	Investigational Site Number : 105	Canberra	Australian Capital Territory
Australia	Investigational Site Number : 101	Clayton	Victoria
Australia	Investigational Site Number : 106	Parkville	Victoria
Australia	Investigational Site Number : 103	Perth	Western Australia
Australia	Investigational Site Number : 104	Sydney	New South Wales
Australia	Investigational Site Number : 102	Woolloongabba	Queensland
Bulgaria	Investigational Site Number : 213	Pleven
Bulgaria	Investigational Site Number : 214	Sofia
Bulgaria	Investigational Site Number : 211	Varna
Canada	Investigational Site Number : 1162	Montreal	Quebec
Canada	Investigational Site Number : 1161	Toronto	Ontario
Czechia	Investigational Site Number : 431	Brno
Czechia	Investigational Site Number : 433	Hradec Kralove
Czechia	Investigational Site Number : 434	Ostrava - Poruba
Czechia	Investigational Site Number : 432	Praha 2
Netherlands	Investigational Site Number : 727	Rotterdam
Netherlands	Investigational Site Number : 728	s-Gravenhage
Norway	Investigational Site Number : 542	Bergen
Norway	Investigational Site Number : 541	Gralum
United Kingdom	Investigational Site Number : 984	Birmingham
United Kingdom	Investigational Site Number : 981	Leicester	Leicestershire
United Kingdom	Investigational Site Number : 980	London	London, City Of
United Kingdom	Investigational Site Number : 983	London	London, City Of
United States	RCCA MC LLC Site Number : 1091	Bethesda	Maryland
United States	Beth Israel Deaconess Medical Center Site Number : 1099	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center Site Number : 1092	Boston	Massachusetts
United States	Pitt County Memorial Hospital Site Number : 1095	Greenville	North Carolina
United States	Mid Michigan Medical Center Site Number : 1086	Midland	Michigan
United States	New York Presbyterian Hospital/Weill Cornell Medical Center Site Number : 1097	New York	New York
United States	Bleeding and Clotting Disorders Institute Site Number : 1087	Peoria	Illinois
United States	Seattle Cancer Care Alliance Site Number : 1098	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Principia Biopharma, a Sanofi Company

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Canada,  Czechia,  Netherlands,  Norway,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A and B: Incidence of Treatment Emergent Adverse Events (Safety Outcome Measure)	Including clinically significant changes in physical examination, laboratory tests, electrocardiogram (ECG), and vital signs.	24 weeks of treatment, long term extension and 4 weeks of follow up post last dose]
Primary	Part A: Consecutive Increased Platelet Counts (Efficacy Outcome Measure)	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.	24 weeks
Primary	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 after 10 weeks of active treatment.	24 weeks
Secondary	Part A: Percent of weeks with platelet counts = 50,000/µL by dose level and overall		24 weeks
Secondary	Part A: Proportion of patients with 4 out of the final 8 platelet counts = 50,000/µL across all dose levels		24 weeks
Secondary	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
Secondary	Part A: Number of weeks with platelet counts =50,000/µL across all dose levels.		24 weeks
Secondary	Part A: Number of weeks with platelet counts =30,000/µL across all dose levels		24 weeks
Secondary	Part A: Time to first platelet count =50,000/µL across all dose levels		24 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	Part B: Proportion of patients receiving rescue medication		24 weeks
Secondary	Part B: Change from baseline in ITP Bleeding Assessment Tool (ITP-BAT)		24 weeks
Secondary	Part A: Proportion of patients receiving rescue medication at each dosing level and overall		24 weeks
Secondary	Part A: Proportion of patients with a Grade 2 or higher bleeding event at each dosing level and overall		24 weeks
Secondary	Part A: Bleeding scale (ITP-BAT scale) at the end of treatment period for each dosing level		24 weeks
Secondary	Part A and B: Plasma PK parameters of rilzabrutinib		Up to long term extension and 4 weeks of follow up post last dose