Rilzabrutinib versus placebo in adults and adolescents with persistent or chronic immune thrombocytopenia: LUNA 3 phase III study

David J Kuter; James B Bussel; Waleed Ghanima; Nichola Cooper; Terry Gernsheimer; Michele P Lambert; Howard A Liebman; Michael D Tarantino; Michelle Lee; Hailing Guo; Ahmed Daak

doi:10.1177/20406207231205431

Rilzabrutinib versus placebo in adults and adolescents with persistent or chronic immune thrombocytopenia: LUNA 3 phase III study

Ther Adv Hematol. 2023 Oct 18:14:20406207231205431. doi: 10.1177/20406207231205431. eCollection 2023.

Authors

David J Kuter¹, James B Bussel², Waleed Ghanima^{3

4}, Nichola Cooper⁵, Terry Gernsheimer⁶, Michele P Lambert⁷, Howard A Liebman⁸, Michael D Tarantino⁹, Michelle Lee¹⁰, Hailing Guo¹⁰, Ahmed Daak¹¹

Affiliations

¹ Hematology Division, Massachusetts General Hospital, Harvard Medical School, Bartlett Hall 150, 140 Blossom Street, Boston, MA 02114-2603, USA.
² Division of Pediatric Hematology/Oncology, Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA.
³ Østfold Hospital Trust, Grålum, Norway.
⁴ Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁵ Department of Immunology and Inflammation, Imperial College London, London, UK.
⁶ University of Washington Medical Center and Fred Hutchinson Cancer Center, Seattle, WA, USA.
⁷ Department of Pediatrics, Children's Hospital of Philadelphia Division of Hematology and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
⁸ Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁹ The Bleeding and Clotting Disorders Institute, University of Illinois College of Medicine Peoria, Peoria, IL, USA.
¹⁰ Sanofi, Bridgewater, NJ, USA.
¹¹ Sanofi, Cambridge, MA, USA.

Abstract

Background: Immune thrombocytopenia (ITP) is characterized by primarily autoantibody-mediated platelet destruction and impaired platelet production resulting in thrombocytopenia and an increased risk of bleeding. Other manifestations include increased risk of thrombosis and diminished quality of life. Current treatment approaches are directed toward lowering the rate of platelet destruction or stimulating platelet production to prevent bleeding. Rilzabrutinib is an oral, reversible, potent Bruton tyrosine kinase inhibitor that was specifically designed to treat immune-mediated diseases and mediates its therapeutic effect through a dual mechanism of action: (1) inhibiting B-cell activation and (2) interrupting antibody-coated cell phagocytosis by Fc gamma receptor in spleen and liver. A 24-week dose-finding phase I/II study of rilzabrutinib in patients with ITP showed a 40% platelet response (⩾2 consecutive platelet counts of ⩾50 × 10⁹/L and increase from baseline ⩾20 × 10⁹/L without rescue medication use) and a well-tolerated safety profile with only grade 1/2 transient adverse events across dose levels.

Objectives: Assess the efficacy and safety of oral rilzabrutinib in adult and adolescent patients with persistent or chronic ITP.

Design: Rilzabrutinib 400 mg BID is being evaluated in the ongoing LUNA 3 multicenter, double-blind, placebo-controlled phase III study.

Methods and analysis: The primary endpoint is durable platelet response, defined as achieving platelet counts of ⩾50 × 10⁹/L for at least two-thirds of ⩾8 available weekly scheduled platelet measurements during the last 12 weeks (including ⩾2 available measurements within the last 6 weeks) of the 24-week blinded treatment period in the absence of rescue therapy.

Ethics: Ethical guidelines and informed consent are followed.

Discussion: The LUNA 3 trial will further investigate rilzabrutinib's safety and efficacy in adult and adolescent patients, with the primary goal of addressing a major objective in treating patients with ITP: durability of platelet response.

Trail registration: ClinicalTrials.gov NCT04562766: https://clinicaltrials.gov/ct2/show/NCT04562766; EU Clinical Trials Register EudraCT 2020-002063-60: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2020-002063-60.

Keywords: B cells; BTK inhibition; autoimmunity; bleeding; immune thrombocytopenia; platelets; rilzabrutinib.

Associated data

ClinicalTrials.gov/NCT04562766