A study published in The Lancet Hematology evaluated the efficacy and safety of deucrictibant for the on-demand treatment of hereditary angioedema (HAE) attacks.
Hereditary angioedema (HAE) is a rare condition characterized by recurrent episodes of severe swelling of the skin and mucous membranes. These attacks generally become more frequent after puberty, and continue throughout life, often affecting the skin, gastrointestinal tract, and upper airway. Triggers for these episodic HAE attacks vary but may include emotional and physical stressors, including dental procedures. HAE may be caused by genetic changes in the SERPING1 gene (also called the C1NH gene) or in the F12 gene. In some cases, the genetic cause is not yet certain.
Deucrictibant is an orally bioavailable bradykinin B2 receptor antagonist currently being developed for prophylaxis and on-demand treatment of HAE attacks. The RAPIDe-1 clinical trial (NCT04618211) was a double-blind, randomized, placebo-controlled, crossover, dose-ranging, phase 2 trial that recruited adults ages 18 to 75 years with HAE type 1 or 2. Participants were required to have experienced two or more attacks within the past 2 months or three or more attacks within the past 4 months before screening.
Patients were randomly assigned to receive oral deucrictibant (immediate-release capsule) 10 mg, 20 mg, or 30 mg during an attack-free period to assess pharmacokinetics and safety in the part 1 of the study. In part 2, patients received a crossover treatment sequence of two administrations of the same deucrictibant dose (10 mg, 20 mg, or 30 mg) and one of placebo to treat three investigator-confirmed HAE attacks.
A total of 89 patients were screened, of whom 74 were randomly assigned. For the primary analysis set, the median follow-up was 130 days for the deucrictibant 10 mg group, 166.5 days for the deucrictibant 20 mg group, and 172 days for the deucrictibant 30 mg group. The primary efficacy analysis included 147 attacks in 62 patients. Least squares mean differences of change in visual analog scale 3 (VAS-3) score between deucrictibant and placebo was −16.75 for 10 mg, −15.02 for 20 mg, and −16.28 for 30 mg.
In part 1, all treatment-emergent adverse events were grades 1 or 2, with the most common being headache and nasopharyngitis in the deucrictibant 30 mg group. In part 2, no single treatment-emergent adverse event was reported by two or more patients in any treatment group. Most adverse events were considered unrelated to the study drug and there were no grade 3 or worse adverse events.
To learn more about HAE and other rare genetic conditions, visit https://checkrare.com/diseases/congenital-and-genetic-conditions/