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. Approval was obtained from WIRB and informed consent obtained from all subjects. nf-C1 INH was administered prophylactically at 1000 U IV every 3 to 7 days. Subjects were also eligible to receive treatment with nf-C1 INH for acute attacks. Subjects were instructed to document 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 nf-C1 INH 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 nf-C1 INH varied (range: 8 to 959 days), 73% received nf-C1 INH 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, laboratory analysis demonstrated persistent rise in C1 INH antigenic and functional levels following nf-C1 INH therapy. Of 74 subjects tested, there were no detectable anti-C1 INH antibodies following C1 INH administration. Adverse events most frequently reported related to nf-C1 INH 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 nf-C1 INH. There were no severe hypersensitivity reactions related to nf-C1 INH. There was no evidence of transmission of HBV, HCV, or HIV during this study.
Conclusions: Administration of nf-C1 INH reduced the median monthly HAE attack rate. The distribution of monthly attack rates per subject over a 1-year period showed persistent effects of prophylactic nf-C1 INH. These data support the safety and efficacy of nf-C1 INH for routine prophylaxis of HAE attacks.