Immune thrombocytopenia (ITP) is an autoimmune disease associated with autoantibody-mediated platelet destruction and impaired platelet production, resulting in thrombocytopenia and a predisposition to bleeding. The ongoing, global phase 1/2 study showed that rilzabrutinib, a Bruton tyrosine kinase inhibitor specifically developed to treat autoimmune disorders, could be an efficacious and well-tolerated treatment for ITP. Clinical activity, durability of response, and safety were evaluated in 16 responding patients who continued rilzabrutinib 400 mg twice daily in the long-term extension (LTE) study. At LTE entry, the median platelet count was 87 × 109/L in all patients, 68 × 109/L in those who had rilzabrutinib monotherapy (n = 5), and 156 × 109/L in patients who received concomitant ITP medication (thrombopoietin-receptor agonists and/or corticosteroids, n = 11). At a median duration of treatment of 478 days (range, 303-764), 11 of 16 patients (69%) continued to receive rilzabrutinib. A platelet count of ≥50 × 109/L was reported in 93% of patients for more than half of their monthly visits. The median percentage of LTE weeks with platelet counts ≥30 × 109/L and ≥50 × 109/L was 100% and 88%, respectively. Five patients discontinued concomitant ITP therapy and maintained median platelet counts of 106 × 109/L at 3 to 6 months after stopping concomitant ITP therapy. Adverse events related to treatment were grade 1 or 2 and transient, with no bleeding, thrombotic, or serious adverse events. With continued rilzabrutinib treatment in the LTE, platelet responses were durable and stable over time with no new safety signals. This trial is registered at www.clinicaltrials.gov as #NCT03395210 and www.clinicaltrialsregister.eu as EudraCT 2017-004012-19.

1st Department of Medicine Department of Haematology 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic

4th Department of Internal Medicine and Hematology Faculty of Medicine University Hospital of Hradec Kralove Hradec Kralove Czech Republic

Barts Health NHS Trust The Royal London Hospital London United Kingdom

Canberra Hospital Garran Australia

Clinic of Hematology University Hospital Pleven Bulgaria

Department of Hemato Oncology Faculty of Medicine University of Ostrava Ostrava Czech Republic

Department of Hemato Oncology University Hospital Ostrava Czech Republic

Department of Immunology and Inflammation Imperial College London United Kingdom

Department of Internal Medicine Hematology and Oncology Masaryk University Hospital Brno Czech Republic

Erasmus MC University Medical Center Rotterdam The Netherlands

Hematology Division Massachusetts General Hospital Harvard Medical School Boston MA

Leicester Royal Infirmary Leicester United Kingdom

Monash Medical Centre Clayton Australia

Østfold Hospital Foundation Gralum Norway and Institute of Clinical Medicine University of Oslo Oslo Norway

Perth Blood Institute Murdoch University Perth Australia

Princess Alexandra Hospital Woolloongabba Australia

Sanofi Cambridge MA

University Multiprofile Hospital for Active Treatment St Marina Varna Varna Bulgaria

University of Washington and Fred Hutchinson Cancer Center Seattle WA

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An adaptive, open-label, dose-finding, phase 1/2 study investigating the safety, pharmacokinetics, and clinical activity of rilzabrutinib (PRN1008), an oral BTK inhibitor, in patients with relapsed immune thrombocytopenia (EudraCT Number: 2017-004012-19) https://www.clinicaltrialsregister.eu/ctr-search/search?query=2017-004012-19 Accessed 1 October 2022.

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Efficacy and Safety Results With Rilzabrutinib, an Oral Bruton Tyrosine Kinase Inhibitor, in Patients With Immune Thrombocytopenia: Phase 2 Part B Study

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ClinicalTrials.gov
NCT03395210

EudraCT
2017-004012-19