D2.497 - Oral Deucrictibant Immediate-Release Capsule for On-Demand Treatment of Hereditary Angioedema Attacks: Results of the Phase 3 RAPIDe-3 Trial

Hereditary angioedema (HAE) attacks are caused by excess bradykinin activating bradykinin B2 receptors. Deucrictibant is a potent, selective, orally administered antagonist of the bradykinin B2 receptor under development for both prophylactic and on-demand treatment (ODT) of bradykinin-mediated angioedema attacks. The pivotal RAPIDe-3 trial investigated the efficacy and safety of deucrictibant immediate-release (IR) capsule for ODT of HAE attacks.

RAPIDe-3 (NCT06343779) was a global, Phase 3, randomized, double-blind, placebo-controlled trial in adolescent and adult participants (≥12 to ≤75 years old) with HAE. Participants self-administered oral deucrictibant IR capsule 20 mg or placebo, in a crossover design, to treat two qualifying attacks, including non-severe laryngeal attacks without breathing difficulties or stridor. The primary endpoint was time to onset of symptom relief, defined as a Patient Global Impression of Change (PGI-C) rating of at least “a little better” for two consecutive timepoints within 12 hours post-treatment. Secondary endpoints included time to substantial symptom relief, defined as PGI-C rating of at least “better” for 2 consecutive timepoints within 12 hours post-treatment, and time to complete resolution of attack manifestations, defined as PGI of severity (PGI-S) rating of “none” within 48 hours post-treatment. Safety outcomes assessed treatment-emergent adverse events (TEAEs).

RAPIDe-3 enrolled 134 participants across 6 continents. The primary efficacy analysis set included 88 participants with paired attacks treated with deucrictibant IR capsule and placebo. Median (95% CIs) time to onset of symptom relief was significantly reduced with deucrictibant IR capsule (1.28 hours [1.05 to 1.52]) versus placebo (>12 hours [5.82 to >12]; p<0.0001). Median (95% CIs) time to substantial symptom relief was also significantly reduced with deucrictibant IR capsule (2.85 hours [2.08 to 3.35]) versus placebo (>12 hours [10.30 to >12]; p<0.0001). Complete resolution was achieved significantly faster with a median (95% CIs) time of 11.95 hours (8.61 to 21.79) with deucrictibant IR capsule versus >48 hours (>48 to >48) with placebo (p<0.0001). Deucrictibant IR capsule was generally well tolerated, with no serious treatment-related TEAEs reported.

In the Phase 3 RAPIDe-3 placebo-controlled trial, oral deucrictibant IR capsule provided faster onset of symptom relief and complete resolution.