Long-term safety of Prolastin®-C, an alpha1-proteinase inhibitor, in Japanese patients with alpha1-antitrypsin deficiency
Kuniaki Seyama, Masaru Suzuki, Sadatomo Tasaka, Toshihiro Nukiwa, Tadashi Sato, Satoshi Konno, Susan Sorrells, Junliang Chen, Maria Esperança Aragonés, Hitoshi Minamino, Kuniaki Seyama, Masaru Suzuki, Sadatomo Tasaka, Toshihiro Nukiwa, Tadashi Sato, Satoshi Konno, Susan Sorrells, Junliang Chen, Maria Esperança Aragonés, Hitoshi Minamino
Abstract
Background: Safety and pharmacokinetics (PK) of alpha1-proteinase inhibitor, modified process (Alpha-1 MP), was evaluated in a clinical trial of Japanese patients with alpha1-antitrypsin deficiency (AATD). The present study aimed to evaluate the long-term safety of weekly intravenous infusions of 60 mg/kg Alpha-1 MP in Japanese patients with AATD.
Methods: This was a multi-center, open-label extension (OLE) study that enrolled adult patients with AATD, who had completed the preceding safety and PK clinical trial. Patients were administered with Alpha-1 MP (60 mg/kg) weekly, for 52 weeks, and this could be renewed annually. Alpha1-MP trough levels (Cmin) were evaluated, and safety endpoints include: treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), TEAEs potentially related to Alpha-1 MP, chronic obstructive pulmonary disease (COPD) exacerbations, laboratory parameters, vital signs, and pulmonary function tests (forced expiration volume in 1 s [FEV1] and forced vital capacity [FVC]).
Results: Four patients underwent Alpha-1 MP intravenous infusions at a mean (SD) of 210.8 (9.54) for 213 weeks (four years), with a Cmin of 55.73 (4.99) mg/dL. A total of fifty-four TEAEs were reported in four patients, in which most of them were mild (n = 52, 96.3%). Two patients had five SAEs, and all were unrelated to treatment. Three mild TEAEs were potentially related to treatment with Alpha-1 MP. No clinically significant findings in laboratory parameters, COPD exacerbations, or vital signs were observed. There were no identifiable differences in FEV1 and FVC throughout the study period.
Conclusions: Long-term weekly intravenous infusions of 60 mg/kg Alpha-1 MP are generally safe and well-tolerated in Japanese patients with AATD.
Clinicaltrials: GOV: NCT02870348; JAPIC CTI: JapicCTI-163194.
Keywords: Alpha(1)-antitrypsin deficiency; Alpha(1)-proteinase inhibitor; Augmentation therapy; Safety.
Conflict of interest statement
Conflict of interest Maria Esperança Aragonés is a full-time employee of Grifols. Susan Sorrells, Junliang Chen, and Hitoshi Minamino are former full-time employees of Grifols. Masaru Suzuki and Satoshi Konno have received research support from Novartis Pharmaceutical Co. Kuniaki Seyama, Sadatomo Tasaka, Tadashi Sato, and Toshihiro Nukiwa declare no conflict of interest.
Copyright © 2022 [The Author/The Authors]. Published by Elsevier B.V. All rights reserved.
Source: PubMed