CHAPTER-1 PHASE 2 TRIAL OF ORAL BRADYKININ B2 RECEPTOR ANTAGONIST DEUCRICTIBANT FOR HEREDITARY ANGIOEDEMA PROPHYLAXIS

Abstract

Introduction

Deucrictibant is an orally-administered bradykinin B2 receptor antagonist under development for on-demand and prophylactic treatment of HAE attacks.

Methods

CHAPTER-1 (NCT05047185) is an ongoing 2-part Phase 2 study evaluating deucrictibant for long-term prophylaxis of HAE attacks. In part 1, participants received double-blind treatment with placebo or deucrictibant 20mg/day or 40mg/day (immediate-release capsule formulation) for 12 weeks. Thirty-four participants were enrolled. In part 2 (ongoing), participants may receive treatment with open-label deucrictibant 40mg/day. Participants were aged ≥18 and ≤75 years, diagnosed with HAE-1/2, not receiving other prophylactic treatments at the time of screening, and experienced ≥3 attacks within 3 months prior to screening or ≥2 attacks during screening (up to 8 weeks).

Results

In placebo-controlled part 1, the monthly attack rate (primary endpoint) was reduced by 84.5% (P=0.0008) by deucrictibant 40mg/day (least squares mean: 0.30; 95% CI: 0.11, 0.82) vs placebo (1.94; 1.31, 2.87). A ≥50%, ≥70%, and ≥90% reduction in attack rate from baseline was achieved in 9, 8, and 6 of 10 participants receiving deucrictibant 40mg/day vs 2, 2, and 0 of 11 receiving placebo. Forty percent of participants receiving deucrictibant 40mg/day vs 0 receiving placebo were attack-free. Both deucrictibant doses were well-tolerated. Four mild treatment-related treatment-emergent adverse events (TEAEs) were reported by 4 participants: 1 receiving placebo, 2 deucrictibant 20mg/day, and 1 deucrictibant 40mg/day. There were no serious TEAEs, severe TEAEs, or TEAEs leading to treatment discontinuation.

Conclusion

CHAPTER-1 provides evidence on efficacy and safety of deucrictibant for the prevention of HAE attacks, supporting its further development.