Study to Evaluate Rilzabrutinib in Adults and Adolescents With Persistent or Chronic Immune Thrombocytopenia (ITP)

Phase 3Active Not RecruitingNCT04562766

Principia Biopharma, a Sanofi Company232 enrolled

Overview

This is a randomized, double-blind study of rilzabrutinib in patients with persistent or chronic ITP, with an average platelet count of \<30,000/μL (and no single platelet count \>35,000/μL) on two counts at least 5 days apart in the 14 days before treatment begins. Patients will receive rilzabrutinib or placebo 400mg twice daily. For each patient, the study will last up to 60 weeks from the start of the Screening Period to the End of Study (EOS) visit. This includes Screening (up to 4 weeks) through a 12 to 24-week Blinded Treatment Period followed by a 28-week Open-Label Period. Followed by a 4-week post dose follow-up. For adult participants, the maximum duration of the long-term extension (LTE) period will be 12 months from the date of the last adult participant to enter the LTE. For pediatric participants, the maximum duration of the LTE period will be 12 months from the date of the last pediatric participant to enter the LTE.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

232

Conditions

Immune Thrombocytopenia

Interventions

Eligibility

Sex: ALLMin age: 10 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Patients will be male and female with primary ITP with duration of \>6 months in pediatric participants aged 12 to \<18 years (pediatric participants aged 10 to \<12 years will be enrolled in the EU \[EEA countries\] only) and duration of \>3 months in ages 18 years and above 2. Patients who had a response (achievement of platelet count ≥50,000/µL) to IVIg/anti-D or CSs that was not sustained and who have documented intolerance, insufficient response or any contra-indication to any appropriate courses of standard of care ITP therapy 3. An average of 2 platelet counts at least 5 days apart of \<30,000/µL during the Screening period and no single platelet count \>35,000/µL, within 14 days prior to the first dose of study drug. \- Pediatric patients must additionally be determined to need treatment for ITP as per clinical assessment by the Investigator. 4. Adequate hematologic, hepatic, and renal function (absolute neutrophil count ≥1.5 X 10\^9/L, AST/ALT ≤1.5 x upper limit of normal \[ULN\], albumin ≥3 g/dL, total bilirubin ≤1.5 x ULN \[unless the patient has documented Gilbert syndrome\], glomerular filtration rate \>50 \[Cockcroft and Gault method for adult and Bedside Schwartz Equation for Pediatric participants\]) 5. Hemoglobin \>9 g/dL within 1 week prior to Study Day 1 6. All contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies 7. Patients must be able to provide written informed consent or informed assent with corresponding informed consent obtained from the patient's guardian and agree to the schedule of assessments Exclusion Criteria: 1. Patients with secondary ITP 2. Pregnant or lactating women 3. History (within 5 years of Study Day 1) or current, active malignancy requiring or likely to require chemotherapeutic or surgical treatment during the study, with the exception of non melanoma skin cancer 4. Transfusion with blood, blood products, plasmapheresis, or use of any other rescue medications with intent to increase platelet count within 14 days before Study Day 1 5. Change in CS and/or TPO-RA dose within 14 days prior to Study Day 1 (more than 10% variation from current doses) 6. Immunosuppressant drugs other than CSs within 5 times the elimination half-life of the drug or 14 days of Study Day 1, whichever is longer 7. Treatment with rituximab or splenectomy within the 3 months prior to Study Day 1 \- Patients treated with rituximab will have normal B-cell counts prior to enrollment 8. Has received any investigational drug within the 30 days before receiving the first dose of study medication, or at least 5 times elimination half-life of the drug (whichever is longer); patient should not be using an investigational device at the time of dosing * Patients who previously received treatment with Bruton's Tyrosine Kinase (BTK) inhibitors (except rilzabrutinib) within 30 days before the first dose of study drug are not eligible * Patients who previously received rilzabrutinib at any time are not eligible 9. History of solid organ transplant 10. Myelodysplastic syndrome 11. Live vaccine within 28 days prior to Study Day 1 or plan to receive one during the study 12. Planned surgery in the time frame of the dosing period

Locations (155)

University of Southern California_Investigational Site Number 84024

Los Angeles, California, United States

UCSF Benioff Children's Hospital San Francisco_Investigational Site Number 84020

San Francisco, California, United States

Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center_Investigational Site Number 84037

Torrance, California, United States

The Oncology Institute of Hope and Innovation_Investigational Site Number 84031

Whittier, California, United States

Children's Hospital Colorado_Investigational Site Number 84025

Aurora, Colorado, United States

Outcomes

Primary Outcomes

Durable platelet response during the last 6 weeks of the 24-week blinded treatment period (not for EU and UK)

Durable platelet response is defined as a proportion of participants able to achieve platelet counts at or above 50,000/μL for ≥ two-thirds of at least 8 non-missing weekly scheduled platelet measurements during the last 12 weeks of the 24-week blinded treatment period in the absence of rescue therapy, provided that at least 2 non-missing weekly scheduled platelet measurements are at or above 50,000/μL.

Time frame: 24 weeks

for EU and UK: Proportion of adult participants able to achieve platelet counts at or above 50,000/μL for at least 8 out of the last 12 weeks of the 24-week blinded treatment period in the absence of rescue therapy

Time frame: 24 weeks

Secondary Outcomes

Number of weeks with platelet count ≥50,000/μL OR between ≥30,000/μL and <50,000/μL and at least doubled from baseline over the 24-week blinded treatment period in the absence of rescue therapy

Time frame: 24 weeks

Number of weeks with platelet counts ≥30,000/μL and at least doubled from baseline over the 24-week blinded treatment period in the absence of rescue therapy

Time frame: 24 weeks

Time to first platelet count of ≥50,000/μL OR between ≥30,000/μL and <50,000/μL and doubled from baseline

Time frame: 24 weeks

Proportion of patients requiring rescue therapy during the 24-week blinded treatment period

Time frame: 24 weeks

Change from baseline on Item 10 of the ITP-Patient Assessment Questionnaire in adult patients (≥18 years) at Week 13

Time frame: From baseline to Week 13

for EU and UK: Change from baseline in Idiopathic Thrombocytopenic Purpura Bleeding Scale (IBLS) assessment at Week 25

Time frame: At Week 25

Proportion of participants who able to achieve stable platelet response, within a period of 24 weeks following initial achievement of the platelet response

Stable platelet response is defined as no 2 scheduled visits, at least 4 weeks apart, with a platelet count less than 50,000/µL, without an intervening visit with a platelet count ≥50,000/µL. Initial platelet response defined as platelet count ≥50,000/μL within 12 weeks of initiation of treatment with rilzabrutinib during the study.

Time frame: 24 weeks

Frequency and severity of Treatment Emergent Adverse Events

Including physical examination, ECG, clinical laboratory test results, vital signs and laboratory tests (serum chemistry, hematology, except for platelet counts included in the primary efficacy endpoint)

Time frame: 52 weeks of treatment, 12 months of long term extension and 4 weeks of follow up post last dose

Frequency and severity of bleeding TEAEs

Time frame: 52 weeks of treatment, 12 months of long term extension and 4 weeks of follow up post last dose

Plasma concentrations of rilzabrutinib

Time frame: Until 52 weeks

Change from baseline on the Symptoms, Bother and Activity domains of the ITP Patient Assessment Questionnaire (ITP-PAQ) in adult patients (≥18 years)

The ITP Patient Assessment Questionnaire™ (ITP-PAQ™) is a disease-specific instrument that was designed to measure the Quality of Life (QoL) of adult patients with immune thrombocytopenia. The items employ a 4-week recall with responses recorded on 4-, 5- or 7-point Likert scales. All item scores are transformed to a 0 to 100 continuum where higher scores represent better QoL and are weighted equally to derive the scale scores.

Time frame: 52 weeks of treatment, 12 months of long term extension and 4 weeks of follow up post last dose

Change from baseline in disease-specific QoL as measured by the Kids' ITP Tools (ITP-KIT) score in pediatric participants

The ITP-KIT include a battery of three disease-specific instruments, a child self-report form designed to be completed by children ≥7 years, a parent proxy report form for children \<7 and a parent impact form. Respondents record their disease experience based on a 1-week recall. The instrument yields a total score which is the summation of the items converted to a 0 to 100 score with higher scores indicating better disease-specific QoL.

Time frame: 52 weeks of treatment, 12 months of long term extension and 4 weeks of follow up post last dose