Clinical trial NCT03395210: A Study of Rilzabrutinib in Adult Patients With Immune Thrombocytopenia (ITP)
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Immune Thrombocytopenia
Immune Thrombocytopenic Purpura
Keywords: ITP
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2018-01-10
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Part A and B: Incidence of Treatment Emergent Adverse Events (Safety Outcome Measure)
timeFrame: 24 weeks of treatment, long term extension and 4 weeks of follow up post last dose]
measure: Part A: Consecutive Increased Platelet Counts (Efficacy Outcome Measure)
timeFrame: 24 weeks
measure: Part B: Sustained Increase in Platelet Counts (Efficacy Outcome Measure)
timeFrame: 24 weeks
Secondary outcomes:
measure: Part A: Percent of weeks with platelet counts ≥ 50,000/μL by dose level and overall
timeFrame: 24 weeks
measure: Part A: Proportion of patients with 4 out of the final 8 platelet counts ≥ 50,000/μL across all dose levels
timeFrame: 24 weeks
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
timeFrame: 24 weeks
measure: Part A: Number of weeks with platelet counts ≥50,000/μL across all dose levels.
timeFrame: 24 weeks
measure: Part A: Number of weeks with platelet counts ≥30,000/μL across all dose levels
timeFrame: 24 weeks
measure: Part A: Time to first platelet count ≥50,000/μL across all dose levels
timeFrame: 24 weeks
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)
timeFrame: 24 weeks
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
timeFrame: 24 weeks
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)
timeFrame: 24 weeks
measure: Part B: Proportion of patients receiving rescue medication
timeFrame: 24 weeks
measure: Part B: Change from baseline in ITP Bleeding Assessment Tool (ITP-BAT)
timeFrame: 24 weeks
measure: Part A: Proportion of patients receiving rescue medication at each dosing level and overall
timeFrame: 24 weeks
measure: Part A: Proportion of patients with a Grade 2 or higher bleeding event at each dosing level and overall
timeFrame: 24 weeks
measure: Part A: Bleeding scale (ITP-BAT scale) at the end of treatment period for each dosing level
timeFrame: 24 weeks
measure: Part A and B: Plasma PK parameters of rilzabrutinib
timeFrame: Up to long term extension and 4 weeks of follow up post last dose
Other outcomes:
Locations:
city: Peoria
country: United States
facility: Bleeding and Clotting Disorders Institute Site Number : 1087
state: Illinois
city: Bethesda
country: United States
facility: RCCA MC LLC Site Number : 1091
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center Site Number : 1092
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center Site Number : 1099
state: Massachusetts
city: Midland
country: United States
facility: Mid Michigan Medical Center Site Number : 1086
state: Michigan
city: New York
country: United States
facility: New York Presbyterian Hospital/Weill Cornell Medical Center Site Number : 1097
state: New York
city: Greenville
country: United States
facility: Pitt County Memorial Hospital Site Number : 1095
state: North Carolina
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance Site Number : 1098
state: Washington
city: Canberra
country: Australia
facility: Investigational Site Number : 105
state: Australian Capital Territory
city: Sydney
country: Australia
facility: Investigational Site Number : 104
state: New South Wales
city: Woolloongabba
country: Australia
facility: Investigational Site Number : 102
state: Queensland
city: Clayton
country: Australia
facility: Investigational Site Number : 101
state: Victoria
city: Parkville
country: Australia
facility: Investigational Site Number : 106
state: Victoria
city: Perth
country: Australia
facility: Investigational Site Number : 103
state: Western Australia
city: Pleven
country: Bulgaria
facility: Investigational Site Number : 213
city: Sofia
country: Bulgaria
facility: Investigational Site Number : 214
city: Varna
country: Bulgaria
facility: Investigational Site Number : 211
city: Toronto
country: Canada
facility: Investigational Site Number : 1161
state: Ontario
city: Montreal
country: Canada
facility: Investigational Site Number : 1162
state: Quebec
city: Brno
country: Czechia
facility: Investigational Site Number : 431
city: Hradec Kralove
country: Czechia
facility: Investigational Site Number : 433
city: Ostrava - Poruba
country: Czechia
facility: Investigational Site Number : 434
city: Praha 2
country: Czechia
facility: Investigational Site Number : 432
city: Rotterdam
country: Netherlands
facility: Investigational Site Number : 727
city: s-Gravenhage
country: Netherlands
facility: Investigational Site Number : 728
city: Bergen
country: Norway
facility: Investigational Site Number : 542
city: Gralum
country: Norway
facility: Investigational Site Number : 541
city: Leicester
country: United Kingdom
facility: Investigational Site Number : 981
state: Leicestershire
city: London
country: United Kingdom
facility: Investigational Site Number : 983
state: London, City Of
city: London
country: United Kingdom
facility: Investigational Site Number : 980
state: London, City Of
city: Birmingham
country: United Kingdom
facility: Investigational Site Number : 984
Study officials:
affiliation: Principia Biopharma
name: Olga Bandman, MD
role: STUDY_DIRECTOR
References:
citation: Kuter DJ, Efraim M, Mayer J, Trneny M, McDonald V, Bird R, Regenbogen T, Garg M, Kaplan Z, Tzvetkov N, Choi PY, Jansen AJG, Kostal M, Baker R, Gumulec J, Lee EJ, Cunningham I, Goncalves I, Warner M, Boccia R, Gernsheimer T, Ghanima W, Bandman O, Burns R, Neale A, Thomas D, Arora P, Zheng B, Cooper N. Rilzabrutinib, an Oral BTK Inhibitor, in Immune Thrombocytopenia. N Engl J Med. 2022 Apr 14;386(15):1421-1431. doi: 10.1056/NEJMoa2110297.
citation: Del Pozo Martin Y. 2021 ASH annual meeting. Lancet Haematol. 2022 Feb;9(2):e92-e93. doi: 10.1016/S2352-3026(21)00384-7. Epub 2021 Dec 16. No abstract available.