PMID- 35970714
OWN - NLM
STAT- MEDLINE
DCOM- 20221103
LR  - 20221103
IS  - 2212-5353 (Electronic)
IS  - 2212-5345 (Linking)
VI  - 60
IP  - 6
DP  - 2022 Nov
TI  - Long-term safety of Prolastin(R)-C, an alpha1-proteinase inhibitor, in Japanese 
      patients with alpha1-antitrypsin deficiency.
PG  - 831-839
LID - S2212-5345(22)00096-X [pii]
LID - 10.1016/j.resinv.2022.07.001 [doi]
AB  - BACKGROUND: Safety and pharmacokinetics (PK) of alpha(1)-proteinase inhibitor, 
      modified process (Alpha-1 MP), was evaluated in a clinical trial of Japanese 
      patients with alpha(1)-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 (C(min)) 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 [FEV(1)] 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 C(min) 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 FEV(1) 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.
CI  - Copyright (c) 2022 [The Author/The Authors]. Published by Elsevier B.V. All rights 
      reserved.
FAU - Seyama, Kuniaki
AU  - Seyama K
AD  - Division of Respiratory Medicine, Juntendo University Faculty of Medicine and 
      Graduate School of Medicine, Tokyo, Japan. Electronic address: 
      kseyama@juntendo.ac.jp.
FAU - Suzuki, Masaru
AU  - Suzuki M
AD  - Department of Respiratory Medicine, Faculty of Medicine and Graduate School of 
      Medicine, Hokkaido University, Sapporo, Japan.
FAU - Tasaka, Sadatomo
AU  - Tasaka S
AD  - Department of Respiratory Medicine, Hirosaki University Graduate School of 
      Medicine, Hirosaki, Japan.
FAU - Nukiwa, Toshihiro
AU  - Nukiwa T
AD  - Professor Emeritus, Tohoku University, Sendai, Japan.
FAU - Sato, Tadashi
AU  - Sato T
AD  - Division of Respiratory Medicine, Juntendo University Faculty of Medicine and 
      Graduate School of Medicine, Tokyo, Japan.
FAU - Konno, Satoshi
AU  - Konno S
AD  - Department of Respiratory Medicine, Faculty of Medicine and Graduate School of 
      Medicine, Hokkaido University, Sapporo, Japan.
FAU - Sorrells, Susan
AU  - Sorrells S
AD  - Grifols Bioscience Research Group, Grifols, Research Triangle Park, NC, USA.
FAU - Chen, Junliang
AU  - Chen J
AD  - Grifols Bioscience Research Group, Grifols, Research Triangle Park, NC, USA.
FAU - Aragones, Maria Esperanca
AU  - Aragones ME
AD  - Grifols Bioscience Research Group, Grifols, Barcelona, Spain.
FAU - Minamino, Hitoshi
AU  - Minamino H
AD  - Grifols Japan KK, Tokyo, Japan.
LA  - eng
SI  - ClinicalTrials.gov/NCT02870348
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
DEP - 20220812
PL  - Netherlands
TA  - Respir Investig
JT  - Respiratory investigation
JID - 101581124
RN  - 0 (alpha 1-Antitrypsin)
SB  - IM
MH  - Adult
MH  - Humans
MH  - *alpha 1-Antitrypsin/adverse effects
MH  - *alpha 1-Antitrypsin Deficiency/drug therapy
MH  - Japan/epidemiology
MH  - Pulmonary Disease, Chronic Obstructive/epidemiology
OTO - NOTNLM
OT  - Alpha(1)-antitrypsin deficiency
OT  - Alpha(1)-proteinase inhibitor
OT  - Augmentation therapy
OT  - Safety
COIS- Conflict of interest Maria Esperanca Aragones 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.
EDAT- 2022/08/16 06:00
MHDA- 2022/11/02 06:00
CRDT- 2022/08/15 22:07
PHST- 2022/05/13 00:00 [received]
PHST- 2022/06/21 00:00 [revised]
PHST- 2022/07/04 00:00 [accepted]
PHST- 2022/08/16 06:00 [pubmed]
PHST- 2022/11/02 06:00 [medline]
PHST- 2022/08/15 22:07 [entrez]
AID - S2212-5345(22)00096-X [pii]
AID - 10.1016/j.resinv.2022.07.001 [doi]
PST - ppublish
SO  - Respir Investig. 2022 Nov;60(6):831-839. doi: 10.1016/j.resinv.2022.07.001. Epub 
      2022 Aug 12.