Open-label Use of Nanofiltered C1 Esterase Inhibitor (human) (nf-C1 INH) for the Prophylaxis of Attacks of Hereditary Angioedema (HAE) in Pediatric Subjects

Introduction: HAE is an autosomal dominant disease of deficient functional C1 inhibitor (nf-C1 INH) manifested by attacks of angioedema commonly involving the gastrointestinal lining, extremities, face, larynx, and genitalia. Symptoms of HAE typically begin in childhood and worsen around puberty. Stanozolol is FDA approved for pediatric prophylaxis but has undesirable AEs, such as masculinization, premature puberty, and premature epiphyseal plate closure. This subset analysis evaluates the use of nf-C1 INH for routine prophylaxis in pediatric subjects with HAE<18 years of age.

Methods: This open-label, multicenter study evaluated subjects aged ≥1 year with a diagnosis of HAE who experienced ≥1 HAE attack per month or had any history of laryngeal edema. nf-C1 INH was administered as prophylactic therapy at a dose of 1000 U IV every 3 to 7 days. Efficacy was based on the frequency of all HAE attacks experienced. Subjects were instructed to record all attacks on a daily basis. Safety was monitored through the recording of AEs and vital signs pre- and post-infusion. Virology and immunogenicity testing were also performed. Approval was obtained from WIRB and informed consent obtained from all subjects.

Results: Prior to enrollment, the 23 children in this study reported a mean HAE attack rate of 4.4 ± 5.7 per month. During nf-C1 INH therapy, the mean monthly attack rate was 0.7 ± 0.98 in those aged 2-5 years old (n=2), 0.4 ± 0.45 in those aged 6-11 years old (n=9), and 0.7 ± 0.90 in those aged 12-17 years old (n=12). Overall, 87% of the 23 children experienced ≤1 HAE attack per month with nf-C1 INH prophylaxis. The only treatment emergent AEs considered to be related was headache, nausea, and infusion-site erythema; none of which were severe. There were no severe hypersensitivity reactions, including anaphylaxis. There were no subjects who discontinued study drug due to AEs, had detectable anti-C1 INH antibodies, or had evidence of transmission of HBV, HCV, or HIV.

Conclusion: nf-C1 INH therapy reduced HAE attacks to ≤1 per month in most of the pediatric subjects in this study. nf-C1 INH was shown to be efficacious and well tolerated when administered for prophylaxis of HAE attacks in pediatric subjects.