Methods: This open-label, multicenter study (47 sites) enrolled 146 subjects aged ≥1 year with HAE and ≥1 attack per month or history of laryngeal edema. C1 INH-nf was administered prophylactically at 1000U IV every 3 to 7 days. Subjects were also eligible to receive treatment with C1 INH-nf for acute attacks. Subjects documented all attacks on a daily basis. Safety was monitored through the recording of AEs, vital signs, virology and anti-C1 INH antibody assessments.
Results: Mean age was 37 years (range 3-82). Pre-enrollment, subjects had a median HAE attack rate of 3.0 per month (range: 0.08-28.0). On C1 INH-nf prophylaxis, the median number of HAE attacks per month was 0.2 (range: 0-4.6) and 86% experienced an average of ≤1 attack per month; 35% reported no attacks during the study. Exposure to C1 INH-nf varied (range: 8 to 959 days), 73% received C1 INH-nf over a period of at least 6 months. For subjects receiving therapy for at least one year, the median attack rate was consistently low at 0.3 per month (range 0-4.0). Irrespective of age, C1 INH antigenic and functional levels persistently increased following C1 INH-nf therapy. Of 74 subjects tested, no anti-C1 INH antibodies were detectable following C1 INH administration. AEs most frequently reported related to C1 INH-nf were: headache 5.5%, nausea 4.1%, rash 2.7%, erythema 2.1% and diarrhea 2.1%. The most commonly reported SAE was HAE attack (11.6%). Five subjects experienced thrombotic SAEs: MI, DVT, PE, and 2 CVA; none of these was considered to be related to C1 INH-nf. There were no severe hypersensitivity reactions related to C1 INH-nf. There was no evidence of transmission of HBV, HCV, or HIV during this study.
Conclusions: C1 INH-nf prophylaxis reduced the median monthly HAE attack rate and showed persistent effects per subject who received prophylaxis over a 1-year period. These data support the safety and efficacy of C1 INH-nf for routine prophylaxis of HAE attacks.