Abstract
Background: Hereditary angioedema (HAE) with C1 inhibitor deficiency (C1-INH) is characterized by swelling of subcutaneous and/or submucosal tissues. Objective: To evaluate efficacy/safety of fixed-dose subcutaneous plasma-derived C1-INH (pdC1-INH) liquid for HAE attack prevention (NCT02584959). Methods: Eligible patients were ≥12 years with ≥2 monthly attacks prescreening or pre–long-term prophylaxis. In a partial crossover design, 80% of patients were randomized to placebo or pdC1-INH liquid for 14 weeks and crossed over from active to placebo or vice versa for another 14 weeks. The remainder were randomized to pdC1-INH liquid for 28 weeks. The primary efficacy endpoint was normalized number of attacks (NNA) versus placebo. Key additional endpoints were the proportion of patients achieving NNA reduction ≥50%, attack severity, number of attack-free days, and safety. Results: Seventy-five patients were randomized and 58 (77%) completed the study. Mean age 41 years; 88% HAE type I. Least-squares means of NNA were reduced from 3.9 with placebo to 1.6 with pdC1-INH (from day 1; P < .0001). Most patients had ≥50% NNA reduction with pdC1-INH (from day 1, 78%). A total of 8.8% of placebo-treated patients were attack-free and 5.3%, 22.8%, and 63.2% had mild, moderate, and severe attacks, respectively; 37.5% of pdC1-INH–treated patients were attack-free and 8.9%, 26.8%, and 26.8% had mild, moderate, and severe attacks, respectively. Treatment-emergent adverse event rates were similar between groups (52% vs 56% for pdC1-INH crossover vs placebo, respectively). Conclusions: Fixed-dose subcutaneous pdC1-INH liquid was superior to placebo in preventing HAE attacks and demonstrated a favorable safety profile.