Recombinant Human C1 Inhibitor (rHC1INH) Is Efficacious and Well Tolerated As Prophylaxis for Prevention of Hereditary Angioedema (HAE) Attacks: A Randomized, Phase 2 Trial

Abstract

rhC1INH is currently administered for the treatment of acute HAE attacks. Repeat rhC1INH treatment for recurrent attacks during open-label extension studies have maintained efficacy while being well tolerated, supporting a potential role for rhC1INH in prophylaxis. A randomized, double-blind, 3-period, crossover study was conducted in patients ≥13 years of age with functional C1INH levels <50% of normal and ≥4 HAE attacks during the previous 3 months. Patients received rhC1INH 50 IU/kg (max, 4200 IU) once or twice weekly or placebo in three, 4-week periods; each treatment was separated by 1 week and symptoms monitored by a daily diary. Primary endpoint was number of HAE attacks per 4-week period. Additional endpoints included percentage of patients with ≥25%, ≥50% (clinical response), or ≥75% reduction in number of HAE attacks versus placebo and number of days with HAE symptoms. Thirty-two patients were randomized (mean age, 45.9 years [range, 16.9–73.5 years]). Mean number of HAE attacks was reduced from 7.2 (placebo) to 4.4 (rhC1INH once weekly; P=0.0004) and 2.7 (rhC1INH twice weekly; P<0.0001). Percentage of patients with ≥25%, ≥50%, and ≥75% reduction in HAE attacks versus placebo was 64.5%, 41.9%, and 19.4% for rhC1INH once weekly and 80.6%, 74.2%, and 41.9% rhC1INH twice weekly, respectively. Number of days with HAE symptoms was lower with rhC1INH twice weekly (5.1 days) and once weekly (8.0 days) versus placebo (10.2 days). rhC1INH was efficacious for the prevention of HAE attacks and data support continued investigation of rhC1INH as prophylaxis.