Pharmacokinetic Profile of Subcutaneous C1-Esterase Inhibitor (C1-INH [SC]) in Adolescent and Adult Patients with Hereditary Angioedema (HAE)
Saturday, March 3, 2018
South Hall A2 (Convention Center)
Dipti K. Pawaskar, PhD, Iris Jacobs, MD, Ingo Pragst, MD, Henrike Feuersenger, PhD
RATIONALE: Subcutaneous C1-INH (HAEGARDA®, CSL Behring) at 60 IU/kg was recently approved by the US FDA as routine prophylaxis to prevent hereditary angioedema (HAE) attacks in adolescents and adults, based on the Phase III COMPACT study. We compared the pharmacokinetics (PK) of C1-INH (SC) in adolescents and adults to determine the effect, if any, of age on C1-INH functional activity.

METHODS: In the COMPACT study, patients self-administered C1-INH (SC) or placebo twice weekly in a double-blind, crossover manner over two 16-week treatment periods. Blood samples were drawn for assessment of C1-INH functional activity at screening; at weeks 1, 3, 5, 8, 11, and 14 of each treatment period; and at the end-of-study visit. Observed C1-INH functional activity was stratified by age group (≤17 years and >17 years) and plotted against time. In addition, PK parameters derived from a population PK analysis of the COMPACT study were evaluated.

RESULTS: Similar C1-INH functional activity over time was observed in patients ≤17 years and >17 years. Mean C1-INH functional activity after administration of C1-INH (SC) 60 IU/kg ranged from 52.9% to 64.9% in adolescents and from 63.9% to 69.4% in adults, well above the critical threshold of 40%. Population PK analysis in subjects with HAE showed that within the age range analyzed (12-72 years), age did not have a clinically relevant effect on the PK of C1-INH functional activity after SC administration.

CONCLUSIONS: Overall, these analyses demonstrate similar PK of C1-INH functional activity after administration of C1-INH (SC) in adolescents and adults.