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

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

This was 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 was completed. Part B treatment dose was 400 mg twice daily.

Study Overview

• Status: Completed
• Conditions: Immune Thrombocytopenia
• Intervention / Treatment: Drug: Rilzabrutinib

Detailed Description

This was 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 enrolled patients with ITP who were refractory or relapsed with no available and approved therapeutic options. Eligible patients had 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 was 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 was allowed to up-titrate their dose after 28 days of PRN1008 therapy, if they did not experience a platelet response or a dose-limiting toxicity (DLT) at the last dose level. Patients who responded to PRN1008 per protocol may enter a long term-extension.

Part B of the study included approximately 25 patients with ITP who had relapsed or had an insufficient response to prior therapies. Eligible patients had a platelet count <30,000/µL on two occasions no less than 7 days apart, within 15 days before treatment began and a platelet count of ≤35,000/µL on Study Day 1 (SD1). The study consisted of a 28-day screening period, 24-week active treatment period, and a long-term extension. After the last dose of PRN1008 there was a 4-week safety follow-up period.

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Australian Capital Territory
    • Canberra, Australian Capital Territory, Australia, 2605
      • Investigational Site Number : 105
  • New South Wales
    • Sydney, New South Wales, Australia, 2139
      • Investigational Site Number : 104
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Investigational Site Number : 102
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Investigational Site Number : 101
    • Parkville, Victoria, Australia, 3050
      • Investigational Site Number : 106
  • Western Australia
    • Perth, Western Australia, Australia, 6005
      • Investigational Site Number : 103
• Bulgaria
  • Pleven, Bulgaria, 5800
    • Investigational Site Number : 213
  • Sofia, Bulgaria, 1431
    • Investigational Site Number : 214
  • Varna, Bulgaria, 9010
    • Investigational Site Number : 211
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5B 1W8
      • Investigational Site Number : 1161
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
      • Investigational Site Number : 1162
• Czechia
  • Brno, Czechia, 62500
    • Investigational Site Number : 431
  • Hradec Králové, Czechia, 50005
    • Investigational Site Number : 433
  • Ostrava - Poruba, Czechia, 70852
    • Investigational Site Number : 434
  • Prague, Czechia, 12808
    • Investigational Site Number : 432
• Netherlands
  • Rotterdam, Netherlands, 3015 GD
    • Investigational Site Number : 727
  • The Hague, Netherlands, 2545 CH
    • Investigational Site Number : 728
• Norway
  • Bergen, Norway, N-5021
    • Investigational Site Number : 542
  • Grålum, Norway, 1714
    • Investigational Site Number : 541
• United Kingdom
  • Birmingham, United Kingdom, B15 2GW
    • Investigational Site Number : 984
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom, LE1 5WW
      • Investigational Site Number : 981
  • London, City of
    • London, London, City of, United Kingdom, E1 2ES
      • Investigational Site Number : 983
    • London, London, City of, United Kingdom, W12 0HS
      • Investigational Site Number : 980
• United States
  • Illinois
    • Peoria, Illinois, United States, 61614-2868
      • Bleeding and Clotting Disorders Institute- Site Number : 1087
  • Maryland
    • Bethesda, Maryland, United States, 20817-1915
      • RCCA MC LLC- Site Number : 1091
  • Massachusetts
    • Boston, Massachusetts, United States, 02114-2603
      • Massachusetts General Hospital Cancer Center- Site Number : 1092
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center- Site Number : 1099
  • Michigan
    • Midland, Michigan, United States, 48670
      • Mid Michigan Medical Center- Site Number : 1086
  • New York
    • New York, New York, United States, 10021
      • New York Presbyterian Hospital/Weill Cornell Medical Center- Site Number : 1097
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Pitt County Memorial Hospital- Site Number : 1095
  • Washington
    • Seattle, Washington, United States, 98109-4405
      • Seattle Cancer Care Alliance Site Number : 1098

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Rilzabrutinib (PRN1008) Daily; 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: Rilzabrutinib; BTK inhibitor; Other Names: PRN1008

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Percentage of Participants Who Achieved 2 or More Consecutive Platelet Counts by Starting Dose Level and Overall	The percentage of participants who achieved 2 or more consecutive platelet counts, separated by at least 5 days, of >=50,000/ microliter (μL) and an increase of platelet count of >=20,000/μL from baseline, by starting dose level and overall, without use of rescue medication in the 4 weeks prior to the latest elevated platelet count. 95% confidence interval (CI) was based on the Clopper-Pearson method. The average of the 2 screening results and the Cycle 1 Day 1 result were used as the baseline value.	Up to 24 Weeks
Part B: Percentage of Participants Who Achieved Platelet Counts >=50,000/μL	The percentage of participants who achieved 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. 95% CI was based on the Clopper-Pearson exact method.	Up to 24 Weeks
Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Related Treatment-Emergent Adverse Events	Adverse event (AE): any untoward medical occurrence in participant or clinical study participant, temporally associated with the use of rilzabrutinib, whether or not considered related to rilzabrutinib. TEAEs: AEs that developed or worsened or became serious on or after the first dose administration of rilzabrutinib (Day 1). Any TEAEs are considered treatment-related TEAEs as per Investigator's evaluation of participant's circumstances surrounding the event, and an evaluation of any potential alternative causes to determine whether an TEAE can be considered as related to the rilzabrutinib.	From first dose of rilzabrutinib (Day 1) up to last dose + 1 (up to 294 days)
Part B: Number of Participants With Treatment-Emergent Adverse Events and Treatment Related Treatment-Emergent Adverse Events	AE any untoward medical occurrence in participant or clinical study participant, temporally associated with the use of rilzabrutinib, whether or not considered related to rilzabrutinib. TEAEs: AEs that developed or worsened or became serious during the treatment-emergent period, defined as any time after the first dose administration of rilzabrutinib (Day 1). Any TEAEs are considered treatment-related TEAEs as per Investigator's evaluation of participant's circumstances surrounding the event, and an evaluation of any potential alternative causes to determine whether an TEAE can be considered as related to rilzabrutinib.	From first dose of rilzabrutinib (Day 1) up to last dose + 1 (approximately 170 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Percentage of Weeks With Platelet Counts >=50,000/μL by Starting Dose Level and Overall	The percentage of weeks in which participants achieved platelet counts >=50,000/μL in the treatment period are summarized here.	Up to 24 Weeks
Part A: Percentage of Participants With 4 Out of the Final 8 Platelet Counts >=50,000/μL by Starting Dose Level and Overall	The percentage of participants who had at least 4 out of the final 8 platelet counts >=50,000/μL are summarized here. The final 8 scheduled platelet counts are the measurements performed in the last 8 weeks of rilzabrutinib (depending on treatment duration, not necessarily from Week 19 to Week 24) in the treatment period. 95% CI was based on the Clopper-Pearson method.	Up to 24 Weeks
Part A: Change From Baseline to the Average of Post Day 1 Platelet Counts by Dose Level and Overall	Average of post Day 1 platelet count is equivalent to average of (average of each participant's post-Day 1 platelet counts), included platelet counts up to 1 day after the date of last dose of rilzabrutinib and excluded platelet counts on or after date of rescue, if applicable. The average of the 2 screening results and the Cycle 1 Day 1 result measured on different date were used as the baseline value.	Baseline and up to 24 Weeks
Part A: Number of Weeks With Platelet Counts >=50,000/μL by Starting Dose Level and Overall	The number of weeks in which participant achieved platelet counts >=50,000/μL in the treatment period are summarized here. The number of weeks is based on the number of scheduled weekly assessments, by study day.	Up to 24 Weeks
Part A: Number of Weeks With Platelet Counts >=30,000/μL by Starting Dose Level and Overall	The number of weeks in which participant achieved platelet counts >=30,000/μL in the treatment period are summarized here. The number of weeks is based on the number of scheduled weekly assessments, by study day.	Up to 24 Weeks
Part A: Time to First Platelet Count >=50,000/μL Across All Dose Levels	Time to first platelet count >=50,000/μL during the treatment period in days was calculated as: (date of first occurrence of platelet count >=50,000/μL - date of first rilzabrutinib dosing) +1.	Up to 24 Weeks
Part B: Number of Weeks With Platelet Counts >= 50,000/μL or >= 30,000/μL and Doubling the Baseline	The number of weeks in which participant achieved platelet counts with thresholds as: >=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) are summarized here. Baseline is defined as the average of 3 platelet counts: 2 qualified screening platelet counts collected in electronic case report form (eCRF) and Week 1 (study day 1) platelet count.	Up to 24 Weeks
Part B: Percentage of Participants Who Achieved 2 or More Consecutive Platelet Counts	Percentage of participants who achieved 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 without use of rescue medication in the 4 weeks prior to the latest elevated platelet count are summarized here. Baseline is defined as the average of 3 platelet counts: 2 qualified screening platelet counts collected in eCRF and Week 1 (study day 1) platelet count. 95% CI was based on the Clopper-Pearson exact method.	Up to 24 Weeks
Part B: Number of Weeks With Platelet Counts >=30,000/μL and Doubling the Baseline	The number of weeks in which participant achieved platelet counts >=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) are summarized here. Baseline is defined as the average of 3 platelet counts: 2 qualified screening platelet counts collected in eCRF and Week 1 (study day 1) platelet count.	Up to 24 Weeks
Part B: Percentage of Participants Who Received Rescue Medication	Rescue medication is defined as any therapy used to rescue a participant (1 of intravenous immunoglobulin [IVIG], high-dose steroids, platelet infusion or anti-D immunoglobulin infusion). Percentage of participants who received rescue medication are summarized here. 95% CI was based on the Clopper-Pearson exact method.	Up to 24 Weeks
Part B: Change From Baseline in Idiopathic Thrombocytopenic Purpura Bleeding Scale (IBLS)	The IBLS is a bleeding assessment score. IBLS comprises of 11 sites for female and 10 sites for male, and each site is scored from 0 (none) to 2 (marked bleeding). The total overall score ranges from 0-22, with higher scores indicating higher presence of marked bleeding. For each participant, an IBLS score at each visit was calculated by taking the average across 11 items (10 for male and postmenopausal women) at 9 anatomical sites (8 for male and postmenopausal women). For each participant, a mean IBLS score was also calculated by taking the average across all post-baseline visits during the 24-week treatment period. IBLS average value ranges from 0 to 2. The smaller the IBLS average value is, the healthier the participants are. For change from baseline, negative value indicates an improvement. The baseline value is defined as the last available value before the first dose rilzabrutinib.	Baseline and up to 24 weeks
Part A: Percentage of Participants Who Received Rescue Medication by Dose Levels and Overall	Rescue medication is defined as any therapy used to rescue a participant (1 of IVIG, high-dose steroids, platelet infusion or anti-D immunoglobulin infusion). The percentage of participants who received rescue medication for each dose level and overall are summarized here. 95% CI was based on the Clopper-Pearson method.	Up to 24 Weeks
Part A: Percentage of Participants With Grade 2 or Higher Bleeding Event by Dose Level and Overall	The percentage of participants with intensity grade 2 or higher bleeding event are summarized for each dose level and overall. The TEAEs with standardized medical dictionary for regulatory activities (MedDRA) query (SMQ) hemorrhages were medically determined for analysis of bleeding events. 95% CI was based on the Clopper-Pearson method.	Up to 24 Weeks
Part A: Number of Participants With Idiopathic Thrombocytopenic Purpura/Immune Thrombocytopenia (ITP) Bleeding Assessment Tool (ITP-BAT) Scale by Dose Level	The ITP-BAT scale comprises of 11 grades from 0 (none) to 2 (marked bleeding), with higher scores indicating higher presence of marked bleeding, assessed at 9 anatomical sites (skin, oral, epistaxis, gastrointestinal [GI], urinary, gynecological [GYN], pulmonary, intracranial hemorrhage [HEM], subconjunctival HEM) by history over the previous week (Hx). In addition, 2 sites (skin and oral), were also assessed by physical examination (PE). The 'worst ever' bleeding experienced at each site was graded using the same system. Here, 0 indicates none; 1 indicates 1-5 bruises and/or scattered petechiae and 2 indicates >5 bruises with size >2 centimeter (cm) and/or diffuse petechiae. Each participant summed up the transformed scores across all 11 sites per visit assessment. The total overall score ranges from 0-22 with the higher score indicating worst outcome.	Up to 24 Weeks
Part A: Maximum Observed Plasma Concentration (Cmax) of Rilzabrutinib	Plasma samples were collected at specified timepoints to determine Cmax of rilzabrutinib.	Day 1 of Cycles 1, 2, 3, and 5 (each cycle 28 days)
Part A: Time of Observed Maximum Plasma Concentration (Tmax) of Rilzabrutinib	Plasma samples were collected at specified timepoints to determine tmax of rilzabrutinib.	Day 1 of Cycles 1, 2, 3, and 5 (each cycle 28 days)
Part A: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Rilzabrutinib	Plasma samples were collected at specified timepoints to determine AUClast of rilzabrutinib.	Day 1 of Cycles 1, 2, 3, and 5 (each cycle 28 days)
Part A: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Rilzabrutinib	Plasma samples were collected at specified timepoints to determine AUCinf of rilzabrutinib.	Day 1 of Cycles 1, 2, and 3 (each cycle 28 days)
Part A: Elimination Half-Life (t1/2) of Rilzabrutinib	Plasma samples were collected at specified timepoints to determine t1/2 of rilzabrutinib.	Day 1 of Cycles 1, 2, and 3 (each cycle 28 days)
Part A: Apparent Volume of Distribution of the Drug After Oral Administration (Vz/F) of Rilzabrutinib	Plasma samples were collected at specified timepoints to determine Vz/F of rilzabrutinib.	Day 1 of Cycles 1, 2, and 3 (each cycle 28 days)
Part A: Apparent Total Clearance of the Drug From Plasma After Oral Administration (CL/F) of Rilzabrutinib	Plasma samples were collected at specified timepoints to determine CL/F of rilzabrutinib.	Day 1 of Cycles 1, 2, and 3 (each cycle 28 days)
Part B: Plasma Concentration of Rilzabrutinib	Plasma samples were collected at specified timepoints for evaluation of rilzabrutinib pharmacokinetic (PK) concentrations.	Pre-dose and 2 hours post-dose on Days 1, 29, and 57

Collaborators and Investigators

• Sponsor: Principia Biopharma, a Sanofi Company
• Investigators: Study Director: Olga Bandman, MD, Principia Biopharma

Publications and helpful links

General Publications

• 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.
• 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.
• Cooper N, Jansen AJG, Bird R, Mayer J, Sholzberg M, Tarantino MD, Garg M, Ypma PF, McDonald V, Percy C, Kostal M, Goncalves I, Bogdanov LH, Gernsheimer TB, Diab R, Yao M, Daak A, Kuter DJ. Efficacy and Safety Results With Rilzabrutinib, an Oral Bruton Tyrosine Kinase Inhibitor, in Patients With Immune Thrombocytopenia: Phase 2 Part B Study. Am J Hematol. 2025 Mar;100(3):439-449. doi: 10.1002/ajh.27539. Epub 2025 Jan 22.
• Kuter DJ, Mayer J, Efraim M, Bogdanov LH, Baker R, Kaplan Z, Garg M, Trneny M, Choi PY, Jansen AJG, McDonald V, Bird R, Gumulec J, Kostal M, Gernsheimer T, Ghanima W, Daak A, Cooper N. Long-term treatment with rilzabrutinib in patients with immune thrombocytopenia. Blood Adv. 2024 Apr 9;8(7):1715-1724. doi: 10.1182/bloodadvances.2023012044.

Helpful Links

• DFI17124 Plain Language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2018
• Primary Completion (Actual): January 31, 2023
• Study Completion (Actual): December 11, 2025

Study Registration Dates

• First Submitted: December 22, 2017
• First Submitted That Met QC Criteria: January 3, 2018
• First Posted (Actual): January 10, 2018

Study Record Updates

• Last Update Posted (Actual): February 23, 2026
• Last Update Submitted That Met QC Criteria: February 3, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: ITP
• Additional Relevant MeSH Terms: Cytopenia; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Skin Manifestations; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Thrombocytopenia; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hemic and Lymphatic Diseases; Purpura, Thrombocytopenic, Idiopathic
• Other Study ID Numbers: DFI17124; PRN1008-010 (Other Identifier: Principia Biopharma); U1111-1260-4044 (Registry Identifier: ICTRP); 2023-509397-39 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No