BACKGROUND: Recombinant human C1 esterase inhibitor (rhC1-INH) is indicated in the United States for the treatment of acute hereditary angioedema (HAE) attacks in adolescents and adults; it is also indicated in Europe for children aged 2 years and older. A need exists for further insight into potential pharmacokinetic (PK) differences in functional C1-INH levels by age (ie, children, adolescents, and adults).
OBJECTIVE: To perform population PK modeling to predict C1-INH levels by age after by age rhC1-INH administration.
METHODS: Data from a phase 2 pediatric trial (children aged 4-13 years at screening) were added to a database of 6 trials in adults and adolescents. An unpublished population PK model was refined and used to simulate C1-INH exposure.
RESULTS: Analysis included 153 individuals (14 healthy volunteers; 139 patients with HAE) and 1788 functional C1-INH measurements (59 from 20 patients in the pediatric trial). Bodyweight (population weight, 16-128 kg) was a key predictor of C1-INH volume of distribution. Age was not a predictor of C1-INH PK after the inclusion of bodyweight in the model. Simulations of the recommended rhC1-INH dosing regimen (bodyweight <84 kg, 50 U/kg; >=84 kg, 4200 U) revealed that overall C1-INH exposure was comparable among age groups. Predicted peak functional C1-INH concentrations were at or above the lower level of normal (>=0.7 U/mL) for 99.8% of adults (>=18 years), 99.8% of adolescents (14-17 years), and 96.0% of children (2-13 years).
CONCLUSION: The analyses support the same weight-based rhC1-INH dosing for HAE attacks in children as currently recommended for adolescents and adults. These results support clinical trial data, which revealed similar safety and efficacy profiles across these age groups. Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.