Open-label use of Nanofiltered C1 Esterase Inhibitor (human) (nf-C1INH) for treatment of acute 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. HAE typically begins in childhood and worsens around puberty. Children have smaller airways complicating intubation during laryngeal attacks and are likely to suffer from upper respiratory infections which can trigger attacks, emphasizing the importance of appropriate treatment options for this age group.

Methods: Overall, this open-label, multicenter study evaluated subjects aged ≥1 year with a diagnosis of HAE; this subset analysis presents data on subjects aged <18 years. nf-C1-INH treatment was administered as 1000 U IV with a second 1000 U dose 60 minutes later, if needed. The presence of three consecutive assessments of improvement at 15-minute intervals within the 4-hr post-treatment period constituted relief. Safety was monitored through the recording of AEs and vital signs pre- and post-infusion. Viral safety labs and immunogenicity testing were also performed. Approval was obtained from WIRB and informed consent obtained from all subjects.

Results: Twenty-two pediatric subjects experienced a total of 121 HAE attacks, with 89% (108/121) achieving relief within 4 hours of nf-C1 INH administration. 91% (69/76) and 89% (39/44) of attacks in subjects aged 6-11 and aged 12-17 achieved relief within 4 hours of nf-C1INH administration, respectively. A two-year-old subject was given two 500 unit doses for a facial attack and reported symptom relief within 3 hours. Gastrointestinal attacks were the most common HAE manifestation. Of the 64 gastrointestinal attacks in 6-11 and 12-17 year olds, 97% (35/36) and 89% (25/28), respectively, experienced relief within 4 hours. No subjects with a laryngeal attack required intubation. There were no treatment emergent AEs reported as related to nf-C1 INH in these subjects. No subjects discontinued study drug due to AEs, had clinically relevant anti-C1 INH antibodies, or had evidence of transmission of HBV, HCV, or HIV.

Conclusion: Administration of 1000U of nf-C1 INH was well-tolerated and effective for the treatment of acute HAE attacks in children. In addition, intubation due to HAE was avoided in all subjects with a laryngeal attack.