Methods: This open-label, multicenter (29 sites) study enrolled 113 subjects with a diagnosis of HAE. Approval was obtained from WIRB and informed consent obtained from all subjects. Subjects were eligible to receive nf-C1 INH 1000U IV for attacks of angioedema at any anatomic location. Subjects could receive a second dose of nf-C1 INH 1000U if they had not improved by 60 minutes. Documentation of attack occurred every 15 minutes by diary card. The presence of three consecutive assessments of improvement constituted relief. Safety was monitored by recording AEs, vital signs, virology (HBV, HCV, HIV) and anti-C1 inhibitor antibody.
Results: Of the 113 subjects (aged 2-80 years) in this study, 101 received nf-C1 INH for an acute attack, and were included in the efficacy analysis. Twelve received nf-C1 INH for short-term prophylaxis only. A total of 609 attacks in 101 subjects were treated. Median time to beginning of relief of the first attack was 45 minutes. Of 84 laryngeal attacks, none required intubation after receipt of nf-C1 INH. No difference was observed in subject response between children and adults. In subjects treated for >1 attack the efficacy of nf-C1 INH was not reduced; of 15 subjects who had ≥ 10 attacks, the median time to beginning of relief of their 10th attack was 30 minutes. Adverse events were reported in 41% (46/113) of subjects. The majority (87%) were of mild or moderate intensity. The most common (3%-5% of subjects) were sinusitis, nasopharyngitis, streptococcal pharyngitis, HAE, constipation, cough, rash, and bronchitis. There were no severe hypersensitivity reactions, including anaphylaxis, related to nf-C1 INH. HBV, HCV, and HIV testing revealed no evidence of viral transmission. There was no evidence of development of clinically relevant anti-C1 INH antibodies.
Conclusion: nf-C1 INH was safe and effective for the treatment of all HAE attacks. For subjects with >1 attack, the efficacy of nf-C1 INH for the treatment of HAE did not diminish with subsequent repeated administration.