Immune Thrombocytopenia
Conditions
Sponsors
Principia Biopharma, a Sanofi Company
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Part A: 1. Male and female patients, aged 18 to 80 years old (Czech Republic and Norway only: aged 18 to 65 years old) 2. Immune-related ITP (both primary and secondary) 3. Refractory or relapsed patients with no available and approved therapeutic options with a platelet count of count 9 g/dL, AST/ALT =1.5 × ULN, albumin =3 g/dL, total bilirubin =1.5 × ULN, estimated glomerular filtration rate [eGFR] > 60 mL/min (Cockcroft and Gault method) (C1D1 pre-dose may be checked up to Day -3 prior to C1D1) 6. Female patients who are of reproductive potential must agree for the duration of active treatment in the study to use a highly effective means of contraception (hormonal contraception methods that inhibits ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal ligation, vasectomized partner, sexual abstinence when this is in line with the preferred and usual lifestyle of the patient). Unless surgically sterile, postmenopausal females should have menopause confirmed by FSH testing 7. Able to provide written informed consent and agreeable to the schedule of assessments Part B: 1. Male or female patients, aged 18 to 80 years old 2. Patients with immune-related ITP (both primary and secondary) as defined by current guidelines with at least 3 months duration 3. Patients who had a response (achievement of platelet count = 50,000/µL) to IVIg/anti-D or corticosteroid that was not sustained and failed at least one other ITP therapy (that was not IVIg or corticosteroid) 4. Patients with a platelet count of 9 g/dL, AST/ALT =1.5 × ULN, albumin =3 g/dL, total bilirubin =1.5 × ULN, eGFR >50 mL/min (Cockcroft and Gault method) (pre-dose may be checked up to Day -3) 6. Female patients who are of reproductive potential must agree for the duration of active treatment in the study to use a highly effective means of contraception (hormonal contraception methods that inhibits ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal ligation, vasectomized partner, or true abstinence; when this is in line with the preferred and usual lifestyle of the patient). Unless surgically sterile, postmenopausal females should have menopause confirmed by follicle-stimulating hormone (FSH) testing. 7. Able to provide written informed consent and agreeable to the schedule of assessments Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 67 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 16
Exclusion criteria
Exclusion criteria: Part A: 1. Pregnant or lactating women 2. ECG findings of QTcF > 450 msec (males) or > 470 msec (females), poorly controlled atrial fibrillation (i.e., symptomatic patients or a ventricular rate above 100 beats/min on ECG), or other clinically significant abnormalities 3. History of current, active malignancy requiring or likely to require chemotherapeutic or surgical treatment during the trial, with the exception of non-melanoma skin cancer 4. Transfusion with blood or blood products or plasmapheresis within 2 weeks before Day 1 5. Change in corticosteroid and/or TPO agonist dose within 2 weeks prior to Day 1 (more than 10% variation from Day 1 daily doses) 6. Use of rescue medications other than corticosteroids or TPO in Exclusion Criterion #5 in the two weeks before Day 1 7. Immunosuppressant drugs other than corticosteroids – these drugs should be discontinued for at least 14 days before Day 1 8. Treatment with rituximab or splenectomy within the 3 months prior to Day 1 9. Ongoing need for the use of proton pump inhibitor drugs such as omeprazole and esomeprazole (it is acceptable to change patient to H2 receptor blocking drugs prior to Day 1) 10. Concomitant use of known strong-to-moderate inducers or inhibitors of CYP3A within 3 days or 5 half-lives (whichever is longer) of Day 1 11. Use of CYP3A-sensitive substrate drugs with a narrow therapeutic index within 3 days or 5 half-lives (whichever is longer) of study drug dosing including, but not limited to, alfentanil, astemizole, cisapride, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, or terfenadine 12. Planned or concomitant use of any anticoagulants and platelet aggregation inhibiting drugs such as aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), thienopyridenes (within 14 days of planned dosing through end of follow-up) 13. 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 14. Current drug or alcohol abuse 15. Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate study drug absorption 16. History of solid organ transplant 17. Positive for screening for HIV, hepatitis B (surface antigen and core antibodies unrelated to vaccination), or hepatitis C (anti-HCV antibody confirmed with HCV RNA) 18. History of serious infections requiring intravenous therapy within the last 3 months before Day 1 19. Clinically significant cognitive dysfunction (= Grade 1) or medical history suggestive of increased risk for cognitive dysfunction during the study 20. Live vaccine within 28 days prior to Day 1 or plan to receive one during the study 21. Planned surgery in the time frame of the dosing period 22. Any other clinically significant disease, condition, or medical history that, in the opinion of the Investigator, would interfere with patient safety, study evaluations, and/or study procedures Part B: 1. Pregnant or lactating women 2. ECG findings of QTcF > 450 msec (males) or > 470 msec (females), poorly controlled atrial fibrillation (i.e., symptomatic patients or a ventricular rate above 100 beats/min on ECG), or other clinically significant abnormalities 3. History (within 5 years of SD1) or current, active malignancy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Part A: • Effect of rilzabrutinib on platelet autoantibody levels • Effect of rilzabrutinib on markers of hemolysis • Effect of rilzabrutinib on thrombopoietin (TPO) levels • Effect of rilzabrutinib on quality of life (QoL) using the Euro-QoL 5-Dimension Visual Analog Scale (EQ-5D VAS) • Plasma metabolite analysis of rilzabrutinib Part B: • To explore effect of rilzabrutinib on markers of hemolysis • To explore effect of rilzabrutinib on thrombopoietin (TPO) levels • To explore effect of rilzabrutinib on IgG, IgG1, IgG4, IgM, IgE levels • To explore effect of rilzabrutinib on quality of life (QOL) using the EQ-5D VAS and Immune Thrombocytopenic Purpura Patient Assessment Questionnaire (ITP-PAQ);Primary end point(s): Outcome Measures of the Study: Part A: Primary Safety endpoints: Safety will be assessed by the incidence, severity and relationship of TEAEs, including clinically significant changes in physical examination, laboratory tests, and vital signs. Treatment-emergent adverse events in the post treatment follow-up period will also be assessed and examined for possible relationship to the prior rilzabrutinib treatment. Adverse events (AEs) will be categorized as treatment emergent after the first dose of rilzabrutinib has been received. Primary Efficacy Endpoint: Proportion of patients able to achieve two 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. Outcome Measures of the Study: Part B: Primary Safety endpoints: Safety will be assessed by the incidence, severity and relationship of TEAEs, including clinically significant changes in physical examination, laboratory tests, and vital signs. Bleeding TEAEs will be tabulated and a proportion of patients with a Grade 2 or higher bleeding event will be provided. Primary Efficacy endp | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety Endpoints: • Proportion of patients receiving rescue medication at each dosing level and overall • Proportion of patients with a Grade 2 or higher bleeding event at each dosing level and overall • Bleeding scale (ITP-BAT) at the end of treatment period for each dosing level Efficacy Endpoints: Part A: • Percent of weeks with platelet counts = 50,000/µL by dose level and overall • Proportion of patients with 4 out of the final 8 platelet counts = 50,000/µL across all dose levels • 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 • Number of weeks with platelet counts = 50,000/µL across all dose levels • Number of weeks with platelet counts = 30,000/µL across all dose levels • Time to first platelet count = 50,000/µL across all dose levels 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) • Proportion of all treated patients able to achieve two 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 • 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) • Proportion of patients receiving rescue medication • Change from baseline in ITP Bleeding Assessment Tool (ITP-BAT) Pharmacokinetic Outcome Measures: Plasma PK parameters (maximum observed plasma concentration [Cmax], Tmax, area under the plasma concentration-time curve [AUC], elimination half-life [t½], apparent volume of distribution of the drug after ora | — |
Countries
Australia, Bulgaria, Canada, Czechia, Czech Republic, Netherlands, Norway, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Desk
Principia Biopharma, a Sanofi Company
Outcome results
None listed