RT Journal Article
SR Electronic
T1 Safety, immunogenicity and pharmacokinetics (PK) of a 120 mg/kg/week dose of alpha<sub>1</sub>-proteinase inhibitor in alpha<sub>1</sub>-antitrypsin deficiency
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P4151
VO 42
IS Suppl 57
A1 Michael Campos
A1 Friedrich Kueppers
A1 James Stocks
A1 Charlie Strange
A1 Junliang Chen
A1 Rhonda Griffin
A1 Laurene Wang-Smith
A1 Maria Cruz
A1 Pete Vandeberg
A1 Mark Brantly
YR 2013
UL http://erj.ersjournals.com/content/42/Suppl_57/P4151.abstract
AB Background: The approved dose of alpha1-proteinase inhibitor (alpha1-PI) for treating alpha1-antitrypsin deficiency (AATD) is 60 mg/kg/week intravenously (IV). Although this dose aims to increase serum alpha1-PI levels above a proposed “protective” threshold (11mM), it is still below the normal range in healthy subjects. We report the safety, tolerability, and PK parameters of 120 mg/kg/week IV alpha1-PI (Prolastin®-C).Methods: In this double-blind crossover study, 30 symptomatic AATD patients were randomly assigned to 60 or 120 mg/kg/week IV Prolastin®-C for 8 weeks, and then changed to the alternate dose after a 2-week washout period. Adverse events (AEs) were recorded, plasma was tested for anti-drug antibodies (ADA) and PK parameters of alpha1-PI were measured. In addition, a neutralizing antibody ELISA was developed and validated for potential characterization of ADAs.Results: The higher dose was well tolerated by all subjects and the frequency of AEs did not appear to be dose-dependent. Exacerbation of COPD was the most frequent AE, consistent with the subjects’ diagnoses. Mean steady-state trough serum alpha1-PI concentration after the 120 mg/kg weekly dose was higher than that after the 60 mg/kg dose (27.7μM and 17.3μM, respectively). Plasma samples tested negative for anti-Prolastin®-C antibodies with a screening/confirmatory ELISA assay.Conclusions: The 120 mg/kg/week dose of Prolastin®-C was well tolerated, did not result in an immunogenicity response and achieved favorable physiologic alpha1-PI serum levels. Assessment of the clinical efficacy of this higher dose on the symptoms and progression of AATD is warranted.