PROPHYLACTIC TREATMENT WITH ORAL DEUCRICTIBANT IMPROVES HEREDITARY ANGIOEDEMA DISEASE CONTROL AND HEALTH-RELATED QUALITY OF LIFE

Abstract

Introduction

Hereditary angioedema (HAE) attacks are caused by excess bradykinin activating bradykinin B2 receptors. Deucrictibant is a selective, 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 efficacy and safety of deucrictibant for long-term prophylaxis of HAE attacks. In part 1, participants received double-blinded placebo or deucrictibant 20mg/day or 40mg/day (immediate-release capsule formulation) for 12 weeks. Thirty-four participants were enrolled. In the ongoing part 2, participants receive treatment with open-label deucrictibant 40mg/day. Disease control, health-related quality of life (HRQoL), and patient treatment satisfaction were assessed using Angioedema Control Test (AECT); Patient Global Assessment of Change (PGA-Change) and Angioedema QoL Questionnaire (AE-QoL); and Treatment Satisfaction Questionnaire for Medication (TSQM).

Results

In placebo-controlled part 1, at 12 weeks, 9/10 participants in both deucrictibant 20mg/day and 40mg/day dose-groups had well-controlled disease by AECT vs 3/8 receiving placebo (P=0.0430 both doses). By PGA-Change, 8/10 and 7/9 participants reported feeling “much better” in the deucrictibant 20mg/day and 40mg/day groups vs 1/8 in the placebo group. Mean AE-QoL total score improved from baseline to week 12 by 19.0, 25.9, and 11.9 points in participants receiving deucrictibant 20mg/day, 40mg/day, and placebo. Participants receiving deucrictibant experienced greater treatment satisfaction, with mean TSQM Global Scores of 89.2 and 85.8 with deucrictibant 20mg/day and 40mg/day vs 59.4 with placebo.

Conclusion

Prophylaxis with oral deucrictibant for 12 weeks resulted in improvement in disease control, HRQoL, and treatment satisfaction vs placebo in people with HAE.