RESUMEN
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.
