Long-Term Prophylactic Treatment with Oral Deucrictibant Improved Health-Related Quality of Life in Participants with Hereditary Angioedema: Final Results of the Phase 2 CHAPTER-1 Open-Label Extension Study

Abstract

Rationale: Deucrictibant is a potent, selective, orally administered bradykinin B2 receptor antagonist under development for prophylactic and on-demand treatment of bradykinin-mediated angioedema attacks. During the randomized, placebo-controlled period (RCT) of the two-part phase 2 CHAPTER-1 study (NCT05047185), participants with hereditary angioedema (HAE) reported improved health-related quality of life (HRQoL) with deucrictibant vs placebo from as early as week 4 and through week 12. Final results of the open-label extension (OLE) on the impact of deucrictibant on HRQoL are presented. Method(s): Of 34 participants enrolled, 30 completed the 12-week RCT, during which they self-administered deucrictibant 20 mg/day (n=11), 40 mg/day (n=10), or placebo (n=9), and continued into the OLE and self-administered deucrictibant 40 mg/day. HRQoL was measured using the Patient Global Assessment of Change (PGA-C) and Angioedema QoL Questionnaire (AE-QoL). Result(s): Of the 30 participants who entered the OLE, 21 rolled over into the phase 3 CHAPTER-4 open-label study (NCT06679881). At the time of OLE end, 24 participants had reached at least the week 86 visit. All (100%) participants reported an improvement in PGA-C, indicating improved HRQoL, at week 86 compared with RCT baseline; all reported feeling "much better". The mean AE-QoL total score improved by 26.9 points from RCT baseline to a score of 14.8 points at week 86. The AE-QoL domains showing the greatest improvement with deucrictibant treatment at week 86 were "functioning" and "fear/shame" (39.4- and 35.5-point improvement, respectively). Conclusion(s): The final CHAPTER-1 OLE results provide further evidence on the effects of long-term prophylactic treatment with oral deucrictibant on HRQoL in HAE. Copyright © 2025 Elsevier Inc.