Efficacy, pharmacokinetics, and safety of subcutaneous C1-esterase inhibitor as prophylaxis in Japanese patients with hereditary angioedema: Results of a Phase 3 study

Background: Hereditary angioedema (HAE) is a rare and potentially life-threatening genetic disorder characterized by recurrent attacks of angioedema. HAE types I and II result from deficient or dysfunctional C1-esterase inhibitor (C1–INH). This Phase 3 study assessed the efficacy, pharmacokinetics (PK), and safety of subcutaneous (SC) C1–INH in Japanese patients with HAE. Methods: The prospective, open-label, multicenter, single-arm Phase 3 study recruited patients with HAE types I or II to an initial run-in period, followed by a 16-week treatment period where patients received 60 IU/kg C1–INH (SC) twice weekly. The two primary endpoints were the time-normalized number of HAE attacks per month and C1–INH functional activity at Week 16. Results: Nine patients entered the treatment period and completed the study. Treatment with C1–INH (SC) significantly reduced the mean monthly attack rate from 3.7 during the run-in period to 0.3 during treatment (exploratory p value of within-patient comparison = 0.004). After the last dose of C1–INH (SC) at Week 16, the mean trough concentration of C1–INH was 59.8%, and the mean area under the plasma concentration–time curve to the end of the dosing period and to the last sample were 5317.1 and 13,091.5 h•%, respectively. During the study, there were no deaths, serious adverse events, or adverse events leading to study discontinuation. Conclusions: C1–INH (SC) (60 IU/kg twice weekly) was efficacious and well tolerated as a prophylaxis against HAE attacks in Japanese patients with HAE types I or II, which was supported by the increased and maintained C1–INH functional activity.EudraCT Number 2019-003921-99; JapicCTI-20527