ITP platelet disorder
Conditions
Interventions
Participants will receive one 400 mg tablet of rilzabrutinib or placebo BID in
the double-blind portion of the study. Participants will receive one 400 mg
tablet of rilzabrutinib BID in the open lab
Sponsors
Principia Biopharma, Inc.
Eligibility
Age
2 Years to 64 Years
Inclusion criteria
Inclusion criteria: Patients may be included in the study if ALL of the following criteria are met: 1. Patients will be male and female with primary ITP with duration of >6 months in pediatric participants aged 12 to 3 months in adults aged >=18 years 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 35,000/µL within 14 days prior to the first dose of study drug • Pediatric participants must additionally be determined to need treatment for ITP as per clinical assessment by the Investigator (see Appendix 10.7 for EU [EEA countries] specific requirements). 4. Adequate hematologic, hepatic, and renal function (absolute neutrophil count >=1.5 X 10^9/L, AST/ALT =3 g/dL, total bilirubin 50 [Cockcroft and Gault method]) 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 A) Male participants Male participants are eligible to participate if they agree to the following during the intervention period and for at least 13 weeks after the last administration of study intervention: • Refrain from donating or cryopreserving sperm Plus either: - Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR - Must agree to use contraception/barrier as detailed below - A male condom; the participant should also be advised of the benefit for a female partner to use a highly effective method of contraception (as described in Appendix 13 Contraceptive and barrier guidance of the protocol) as a condom may break or leak when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant B) Female participants A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: • Is a woman of nonchildbearing potential (WONCBP) as defined in Appendix 13 of the protocol. OR • Is a woman of childbearing potential (WOCBP) and agrees to use a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, as described in Appendix 13 of the protocol, during the study intervention period (to be effective before starting the intervention) and for at least 4 weeks after the last administration of study intervention AND agrees not to donate or cryopreserve eggs (ova, oocytes) for the purpose of reproduction during this period. • A WOCBP must have a negative highly sensitive pregnancy test (
Exclusion criteria
Exclusion criteria: Patients will be excluded from the study if any of the following criteria are met: 1. Patients with secondary ITP 2. Pregnant or lactating women 3. Electrocardiogram (ECG) findings for participants: o Aged >=10 and 449 msec (males) or >457 msec (females) o Aged >=16 and 450 msec (males) or >460 msec (females) o Aged >=18 years, of QTcF >450 msec (males) or >470 msec (females), poorly controlled atrial fibrillation (ie, symptomatic participants or a ventricular rate above 100 beats/min on ECG), or other clinically significant abnormalities 4. 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 5. 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 6. Change in CS and/or TPO-RA dose within 14 days prior to Study Day 1 (more than 10% variation from current doses) 7. 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 8. 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 9. Ongoing need for the use of proton pump inhibitor drugs such as omeprazole and esomeprazole (it is acceptable to change participant to histamine 2 receptor blocking drugs prior to Study Day 1) 10. Use of known strong-to-moderate inducers or inhibitors of CYP3A within 14 days or 5 half-lives (whichever is longer) of Study Day 1 and until the end of the active treatment period 11. Planned or concomitant use of any anticoagulants and platelet aggregation inhibiting drugs such as aspirin (except for low dose aspirin up to 100 mg per day), nonsteroidal anti-inflammatory drugs, and/or thienopyridines within 14 days of Study Day 1 and until the end of the active treatment period 12. 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); participant should not be using an investigational device at the time of dosing o 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 o Patients who previously received rilzabrutinib at any time are not eligible 13. Current drug or alcohol abuse 14. Refractory nausea and vomiting, malabsorption, external biliary shunt, significant bowel resection, or any other condition that would preclude adequate study drug absorption 15. History of solid organ transplant 16. Positive at Screening for human immunodeficiency virus (HIV), hepatitis B virus (HBV) (surface and core antibodies unrelated to vaccination), or hepatitis C virus (anti-HCV antibody confirmed with Hep C RNA) o Patients who are hepatitis B virus surface antigen (HBsAg) positive will not be eligible. o Patients who are HBsAg negative and hepatitis B core antigen antibody (HBcAb) positive will be tested for HBV surface antibody (HBsAb) a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Efficacy Endpoint (Blinded Treatment Period) • Durable platelet response 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 during the last 6 weeks of the 24-week blinded treatment period; see Appendix 10.7 for country specific definition of durable platelet response (EU [EEA countries] and UK). | — |
Secondary
| Measure | Time frame |
|---|---|
| Key Secondary Efficacy Endpoints (Blinded Treatment Period) • Number of weeks with platelet count >=50,000/µL OR between >=30,000/µL and =30,000/µL and at least doubled from baseline over the 24-week blinded treatment period in the absence of rescue therapy • Time to first platelet count of >=50,000/µL OR between >=30,000/µL and =18 years) at Week 13 See Appendix 10.7 for EU (EEA countries) and UK specific requirements. Other Secondary Endpoints Efficacy Endpoint • Stability of response defined as the proportion of participants able to achieve stable platelet response, which 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, within a period of 24 weeks following initial achievement of the platelet response (initial platelet response defined as platelet count >=50,000/µL within 12 weeks of initiation of treatment with rilzabrutinib during the study) Safety Endpoints • Frequency and severity of TEAEs • Frequency and severity of bleeding TEAEs • Change from baseline in physical examination, ECG, vital signs and clinical laboratory tests results: serum chemistry and hematology (except for platelet counts included in the primary efficacy endpoint) Pharmacokinetic Endpoints • Plasma concentrations of rilzabrutinib Quality of Life (QOL) Endpoints • Change from baseline on the Symptoms, Bother and Activity domains of the ITP Patient Assessment Questionnaire (ITP-PAQ) in adult participants (>=18 years) • Change from baseline in disease-specific QoL as measured by the Kids* ITP Tools (ITP-KIT) score in pediatric participants | — |
Countries
Netherlands
Outcome results
None listed