Long-Term Safety and Efficacy of Oral Deucrictibant for Prophylaxis in Hereditary Angioedema: Final Results of the Phase 2 CHAPTER-1 Open-Label Extension Study

Abstract

Rationale: Deucrictibant is a potent orally administered bradykinin B2 receptor antagonist under development for prophylactic and on-demand treatment of bradykinin-mediated angioedema attacks. The two-part, phase 2 CHAPTER-1 study (NCT05047185) evaluated the efficacy and safety of deucrictibant for prophylaxis of hereditary angioedema (HAE) attacks. Final results of the long-term open-label extension (OLE) are presented. Method(s): CHAPTER-1 included a 12-week randomized controlled trial (RCT) and a 30-month OLE. RCT enrolled 34 participants (>=18 and <=75 years) diagnosed with HAE-1/2. All 30 participants who completed RCT continued into the OLE. These participants self-administered deucrictibant 20 mg/day (n=11), 40 mg/day (n=10), or placebo (n=9) for 12 weeks during the RCT, and deucrictibant 40 mg/day (n=30) during the OLE. Result(s): The final OLE analysis included all 30 participants. Mean (standard deviation, SD) treatment duration in the OLE was 22.2 (8.1) months and maximum deucrictibant exposure during the entire study was 33.4 months. Deucrictibant was generally well tolerated with 1 treatment-related treatment emergent adverse event (TEAE) of mild gamma-glutamyl transferase elevation, no serious treatment-related TEAEs, and no TEAEs leading to study drug discontinuation. Mean (SD) attack rate was 2.18 (1.35) at RCT baseline and on-treatment least squares mean (LSM) attack rate was 0.12 (standard error [SE] 0.04) during the OLE. The LSM (SE) monthly rates of "moderate and severe" attacks and attacks treated with on-demand medication during the OLE were both 0.06 (0.02). Conclusion(s): The final CHAPTER-1 OLE results provide additional evidence on the long-term safety and efficacy of deucrictibant for prophylaxis of HAE attacks. Copyright © 2025 Elsevier Inc.