TY - JOUR
T1 - Deucrictibant for angioedema due to acquired C1-inhibitor deficiency
T2 - A randomized-controlled trial
AU - Petersen, Remy S.
AU - Fijen, Lauré M.
AU - Kelder, Johannes P.
AU - Cohn, Danny M.
N1 - Publisher Copyright: © 2024 The Authors
PY - 2024
Y1 - 2024
N2 - Background: Angioedema 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 swelling in patients with this condition. Deucrictibant is a specific, orally bioavailable, competitive antagonist of the bradykinin B2 receptor currently under investigation for hereditary angioedema. Objective: Our aim was to assess the efficacy and safety of deucrictibant as acute and prophylactic treatment for angioedema due to acquired C1-inhibitor deficiency. Methods: A 2-part, randomized, double-blind, placebo-controlled crossover study was conducted. In Part 1, 4 consecutive angioedema attacks were treated with 3 doses of deucrictibant (10 mg, 20 mg, and 30 mg) or placebo. In Part 2, deucricibant, 20 mg, or placebo was administered twice daily for 2 treatment periods of 8 weeks. Results: Three patients were enrolled; of those 3 patients, 1 completed both study parts and 2 completed only Part 2. In Part 1, a reduction in attack severity was observed in the 3 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 1 self-limiting treatment-emergent adverse event (abdominal pain). Conclusions: Deucrictibant has the potential to effectively and safely treat and prevent angioedema attacks due to acquired C1-inhibitor deficiency.
AB - Background: Angioedema 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 swelling in patients with this condition. Deucrictibant is a specific, orally bioavailable, competitive antagonist of the bradykinin B2 receptor currently under investigation for hereditary angioedema. Objective: Our aim was to assess the efficacy and safety of deucrictibant as acute and prophylactic treatment for angioedema due to acquired C1-inhibitor deficiency. Methods: A 2-part, randomized, double-blind, placebo-controlled crossover study was conducted. In Part 1, 4 consecutive angioedema attacks were treated with 3 doses of deucrictibant (10 mg, 20 mg, and 30 mg) or placebo. In Part 2, deucricibant, 20 mg, or placebo was administered twice daily for 2 treatment periods of 8 weeks. Results: Three patients were enrolled; of those 3 patients, 1 completed both study parts and 2 completed only Part 2. In Part 1, a reduction in attack severity was observed in the 3 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 1 self-limiting treatment-emergent adverse event (abdominal pain). Conclusions: Deucrictibant has the potential to effectively and safely treat and prevent angioedema attacks due to acquired C1-inhibitor deficiency.
KW - Deucrictibant
KW - acquired C1-inhibitor deficiency
KW - acute treatment
KW - angioedema
KW - bradykinin B2 receptor
KW - long-term prophylaxis
KW - randomized controlled trial
UR - http://www.scopus.com/inward/record.url?scp=85189434627&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2024.03.007
DO - 10.1016/j.jaci.2024.03.007
M3 - Article
C2 - 38494092
SN - 0091-6749
JO - Journal of allergy and clinical immunology
JF - Journal of allergy and clinical immunology
ER -