PURPOSE: To assess the safety and tolerability of a new alpha1-proteinase inhibitor (A1-PI) augmentation therapy, Zemaira® (ZLB Behring) [Z(A1-PI)].
METHODS: Two single-dose studies in patients with alpha1-antitrypsin deficiency. Study I: open-label, dose-ranging study using 15 (n=2), 30 (n=5), 60 (n=6) and 120 mg/kg (n=6) functionally active A1-PI. Study II: double-blind, controlled, 2x2 crossover comparison of Z(A1-PI) and an existing A1-PI preparation (Talecris Biotherapeutics) [P(A1-PI)] 60 mg/kg. Adverse events (AEs: mild, moderate or severe), whether or not drug-related, including clinical or laboratory events, and serious AEs were monitored.
RESULTS: 37 subjects (24M, 13F), mean age 47 (29-66) years were treated with Z(A1-PI). Mean baseline A1-PI level was 5.2 μM (3.2-9.4 μM) and mean duration of disease was 3.5 years (0.3-17.8). Emphysema was diagnosed in 27/37 (73%) and mean FEV1 percent predicted was 41.7% (13.3-92.8%). Nineteen subjects treated with Z(A1-PI) (51%) reported one or more treatment-emergent AEs, all of them mild or moderate and none serious. The most frequently reported AEs (≥10%) were injection site hemorrhage (5/37, 14%) and headache (4/37, 11%). Two subjects (Study I) experienced AEs possibly related to Z(A1-PI): dizziness and pruritus in one; headache in the other. The incidence of AEs appeared not to be dose related. In study II, 6 of 18 single infusions of P(A1-PI) were followed by at least one AE; 2 of these were related to treatment with P(A1-PI) (hypotension, headache). There were no relevant differences between Z(A1-PI) and P(A1-PI) in Study II. No clinically significant laboratory findings were reported.
CONCLUSION: Z(A1-PI) appears to be safe and well tolerated and was comparable to P(A1-PI).
CLINICAL IMPLICATIONS: This is the first report of safety of Z(A1-PI) in single doses up to 120 mg/kg functionally active A1-PI. No unexpected safety and tolerability issues were encountered with Z(A1-PI).
DISCLOSURE: James Stocks, Other This research was funded by ZLB Behring LLC.