Deucrictibant for angioedema due to acquired C1-inhibitor deficiency: A randomized-controlled trial

Abstract

BackgroundAngioedema due to acquired C1-inhibitor deficiency is a very rare but serious disease, with an estimated prevalence of 1 per 500,000 persons. There are no approved therapies to treat or prevent angioedema swellings in patients with this condition. Deucrictibant is a specific, orally bioavailable, competitive antagonist of the bradykinin B2 receptor currently under investigation for hereditary angioedema. ObjectiveTo assess the efficacy and safety of deucrictibant as acute and prophylactic treatment for angioedema due to acquired C1-inhibitor deficiency. MethodsA two-part, randomized, double-blind, placebo-controlled crossover study was conducted. In Part 1, four consecutive angioedema attacks were treated with three doses of deucrictibant (10 mg, 20 mg, and 30 mg) or placebo. In Part 2, deucricibant 20 mg or placebo was administered bidaily for two treatment periods of eight weeks. ResultsThree patients were enrolled of which one completed both study parts and two completed only Part 2. In Part 1, a reduction in attack severity was observed in the three attacks treated with deucrictibant as opposed to an increase in severity of the attack treated with placebo. In Part 2, the individual mean monthly attack rates were 2.0, 0.6 and 1.0 during the placebo period and 0.0 across all patients during treatment with deucrictibant. There were no severe adverse events, and one self-limiting treatment-emergent adverse event (abdominal pain). ConclusionsDeucrictibant has the potential to effectively and safely treat and prevent angioedema attacks due to acquired C1-inhibitor deficiency.