LUNA3 Phase III Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial of the Oral BTK Inhibitor Rilzabrutinib in Adults and Adolescents with Persistent or Chronic Immune Thrombocytopenia

• Published in: Blood 2021-11, Vol.138 (Supplement 1), p.1010-1010
• Main Authors: Kuter, David J., Bussel, James B, Cooper, Nichola, Gernsheimer, Terry, Lambert, Michele P., Liebman, Howard, Tarantino, Michael D, Bandman, Olga, Arora, Puneet, Neale, Ann, Burns, Regan, Yao, Mengjie, Ghanima, Waleed
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2021-144504

Background: The autoimmune disorder immune thrombocytopenia (ITP) is characterized by immune-mediated platelet destruction and impaired production, leading to a predisposition to bleeding and diminished quality of life. Although initially responsive to standard therapy, most patients do not attain durable remission or are challenged by long-term tolerability. Rilzabrutinib is the first oral, reversible Bruton tyrosine kinase (BTK) inhibitor that targets mechanisms driving ITP without effects on normal platelet aggregation. Preclinical studies showed simultaneous rapid anti-inflammatory effects of rilzabrutinib and neutralization and prevention of autoantibody signaling (Langrish J Immunol 2021). In an ongoing phase I/II study, the optimal dose of 400 mg bid rilzabrutinib (± concomitant ITP therapy) was well tolerated and resulted in rapid and durable platelet response across several subgroups of patients and with extended treatment. Study Design and Methods: LUNA3 is the first randomized, multicenter, phase III study evaluating the efficacy and safety of rilzabrutinib vs placebo with open-label extension in adult and adolescent patients with persistent or chronic ITP (NCT04562766; EudraCT 2020-002063-60). Eligible patients must have primary ITP for >6 months if aged 12-17 years or >3 months if aged ≥18 years and an average of 2 platelet counts 35×10 9/L) within 2 weeks prior to study treatment. Additionally, patients should have a previous response (platelet count ≥50×10 9/L) to corticosteroids or intravenous immunoglobulin/anti-D that was insufficient or not sustained, or documented intolerance or insufficient response to any appropriate courses of standard-of-care ITP therapy. Randomization is carried out separately for the 2 age groups (12-17 years and ≥18 years), and then patients are stratified by splenectomy status (yes/no) and thrombocytopenia severity (platelet counts