@article {CamposP4151, author = {Michael Campos and Friedrich Kueppers and James Stocks and Charlie Strange and Junliang Chen and Rhonda Griffin and Laurene Wang-Smith and Maria Cruz and Pete Vandeberg and Mark Brantly}, title = {Safety, immunogenicity and pharmacokinetics (PK) of a 120 mg/kg/week dose of alpha1-proteinase inhibitor in alpha1-antitrypsin deficiency}, volume = {42}, number = {Suppl 57}, elocation-id = {P4151}, year = {2013}, publisher = {European Respiratory Society}, abstract = {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 {\textquotedblleft}protective{\textquotedblright} 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{\textregistered}-C).Methods: In this double-blind crossover study, 30 symptomatic AATD patients were randomly assigned to 60 or 120 mg/kg/week IV Prolastin{\textregistered}-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{\textquoteright} 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{\textregistered}-C antibodies with a screening/confirmatory ELISA assay.Conclusions: The 120 mg/kg/week dose of Prolastin{\textregistered}-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.}, issn = {0903-1936}, URL = {https://erj.ersjournals.com/content/42/Suppl_57/P4151}, eprint = {https://erj.ersjournals.com/content/42/Suppl_57/P4151.full.pdf}, journal = {European Respiratory Journal} }