A Phase 1/2, Open-Label, Single-Dose, Multicenter Study to Evaluate the Pharmacokinetics and Safety of Human Plasma-Derived Protein C Concentrate in Japanese Patients with Severe Congenital Protein C Deficiency (SCPCD).

Abstract

Purpose: Severe congenital protein C deficiency (SCPCD) is a rare, life-threatening disorder. Plasma-derived protein C concentrate is recommended for the acute and long-term management of SCPCD; however, data in Japanese patients are lacking. In this study, the pharmacokinetics (PK) and safety of protein C concentrate were investigated in a Japanese population.

Patients and methods: This study was an open-label, phase 1/2, nonrandomized, noncontrolled, multicenter clinical trial in Japanese patients with SCPCD (ClinicalTrials.gov: NCT04984889). Patients received a single intravenous dose (80 IU/kg) of human plasma-derived protein C concentrate. The primary endpoints were plasma protein C activity levels and PK parameters. Secondary endpoints for safety included adverse events (AEs).

Results: All five enrolled patients (mean age, 15.2 years; mean weight, 34.0 kg) received the predefined dose of protein C concentrate and were included in PK and safety analyses. The geometric mean (coefficient of variation [CV]%) maximum concentration (C_max) was 1.679 IU/mL (31.7%) and the geometric mean (CV%) area under the curve (AUC_inf) was 21.88 IU·h/mL (47.1%). The median (range) half-life for protein C in plasma was 10.7 (7.35-12.4) hours. C_max and AUC_inf tended to be higher in older patients (≥20 years old) than in younger patients (<20 years old), whereas half-life was similar regardless of age. One patient had a mild treatment-related AE of pyrexia. No serious AEs or deaths were reported.

Conclusion: PK parameters for protein C concentrate in Japanese patients with SCPCD were determined to be comparable to studies in western populations. A single intravenous 80 IU/kg dose was well tolerated, with no serious treatment-related AEs.