Efficacy and Safety of Beceltinib Capsules in the Treatment of Persistent or Chronic Primary Immune Thrombocytopenia: A Multicenter, Randomized, Open-Label, Phase 1/2 Study

Abstract:

Introduction:

Immune thrombocytopenia (ITP) is a complex autoimmune disease characterized by abnormally low blood platelet count, resulting in an increased risk of bleeding. Beceltinib, an oral irreversible covalent inhibitor of Bruton's tyrosine kinase, has shown potential as a therapeutic approach for ITP. This study aimed to evaluate the efficacy and safety of Beceltinib in adult patients with persistent or chronic ITP.

Methods:

In this multicenter, randomized, open-label, phase 1/2 study, adult patients with primary ITP who had previously failed standard therapy or could not tolerate it were enrolled. Patients were randomly assigned to receive either 50mg, 75mg, or 100mg of Beceltinib twice daily for 24 weeks. The primary endpoint was the proportion of patients achieving platelet counts of ≥50×10⁹/L for at least two consecutive weeks during the treatment period. The secondary efficacy end points were sustained platelet response which defined as the proportion of patients with at least 4 platelet counts≥50×10⁹/L during the last 6 visits within 24 weeks without rescue medication use. Safety monitoring, including adverse events, physical examinations, and bleeding risk assessments, was conducted throughout the trial. Pharmacokinetics and pharmacodynamics of Beceltinib were also explored.

Results:

A total of 32 patients were enrolled in the study, and 13 patients (40.6%) achieved the primary endpoint which is two consecutive platelet counts of at least 50 x 10⁹/L during 24-week treatment period. Out of the responders, 11 patients (84.6%) demonstrated a sustained response, indicating that majority of the patients who positively responded to Beceltinib exhibited continued efficacy. The median cumulative response duration was 22 weeks (interquartile range, 12 to 31). The median time to the first platelet counts of at least≥50×10⁹/L was 3 week (range, 1 to 9). Patients who had responded to glucocorticoids in the past showed better primary platelet response (61.5%, 8 of 13) and sustained platelet response (53.8%, 7 of 13). Dose adjustments were made in some patients, and the effective rate varied across different dose levels. The incidence of adverse reactions was 43.8%, with most being mild (grades 1 or 2). The study demonstrated that Beceltinib was generally well-tolerated by ITP patients.

Conclusion:

This study suggests that Beceltinib may have potential efficacy and safety for the second-line treatment of ITP. The findings provide new treatment options for clinical practice. Further studies are needed to validate these results and assess the long-term effects of Beceltinib in ITP patients.

Fu:Takeda (China) International Trading Co., Ltd: Consultancy, Honoraria, Research Funding.