title: Multi-center study: the biochemical efficacy, safety and tolerability of a new alpha1-proteinase inhibitor, Zemaira.
abstract: Augmentation therapy with a plasma derived alpha l-Proteinase Inhibitor (alpha1 -PI) has been demonstrated to be effective in restoring serum Alpha1 -antitrypsin (AAT)* levels in individuals with AAT Deficiency (note: alpha1 PI and AAT are synonymous). The objective of this study was to demonstrate that the steady-state trough serum alphal-PI levels, achieved by a new plasma derived alpha,-PI (Zemaira, study drug, ZLB Behring LLC, King of Prussia, Pennsylvania, USA), were bioequivalent to those achieved by the currently available alpha-PI therapy, Prolastin (control drug, Bayer Corporation, Berkeley, California, USA), and maintained weekly trough serum antigenic alpha1-PI levels above the protective threshold of 11 microM. This multi-center, controlled study randomized a total of 44 subjects to receive either study or control drug for a 10-week double-blind phase. The control group was then crossed over to receive the study drug for the remainder of the study (14 weeks). The difference in mean trough serum antigenic alpha1-PI level between the treatment groups was 1.45 microM (90% CI-2.77, -0.13), signifying bioequivalence. The mean trough serum antigenic alpha1-PI level in the study drug group was greater than the therapeutic threshold of 11 microM, achieving a level of 17.7 microM during the steady-state period. Treatment-related adverse events (AEs) were seen in 7% and 21% of study and control drug treated subjects, respectively. No documented viral transmission occurred. These results demonstrate that the new plasma derived alpha1-PI (Zemaira) is bioequivalent to the currently available product Prolastin, is well tolerated, and safe with respect to the risk of viral transmission.
authors.affiliation: The University of Texas Health Center at Tyler, 11937 US Hwy 271, Tyler, TX 75708-3154, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Stocks
authors.forename: Mark
authors.initials: M
authors.lastname: Brantly
authors.forename: David
authors.initials: D
authors.lastname: Pollock
authors.forename: Alan
authors.initials: A
authors.lastname: Barker
authors.forename: Friedrich
authors.initials: F
authors.lastname: Kueppers
authors.forename: Charlie
authors.initials: C
authors.lastname: Strange
authors.forename: James F
authors.initials: JF
authors.lastname: Donohue
authors.forename: Robert
authors.initials: R
authors.lastname: Sandhaus
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015842:Serine Proteinase Inhibitors / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013810:Therapeutic Equivalency; D000515:alpha 1-Antitrypsin / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019896:alpha 1-Antitrypsin Deficiency / Q000097:blood / Q000188:drug therapy*
chemical_list: D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin