Results of a Double-Blind, Randomized, Placebo-Controlled Phase 1 Study to Evaluate the Safety and Pharmacokinetics of Anti-Zika Virus Immunoglobulin

• Published in: The American journal of tropical medicine and hygiene 2021-12, Vol.105 (6), p.1552-1562
• Main Authors: White, Jane, Tunga, Priya, Anderson, Deborah M, Iledan, Ken, Loreth, Tobi, Parrera, Geraldine S, Astacio, Hugo, Drobic, Bojan, Richardson, Jason S
• Format: Article
• Language: English
• Subjects: Adult; Double-Blind Method; Double-blind studies; Female; Humans; Immunization, Passive - methods; Immunoglobulin G - immunology; Immunoglobulin G - therapeutic use; Immunoglobulins; Male; Middle Aged; Pharmacokinetics; Young Adult; Zika virus; Zika Virus - immunology; Zika Virus Infection - therapy
• ISSN: 0002-9637; 1476-1645
• DOI: 10.4269/ajtmh.20-1578

Zika virus (ZIKV) is transmitted primarily through infected Aedes aegypti or Aedes albopictus mosquitoes. ZIKV infection during pregnancy was linked to adverse fetal/infant outcomes, including microcephaly, brain anomalies, ocular disorders, intrauterine growth restriction, and other congenital malformations. Human anti-Zika virus immunoglobulin (ZIKV-Ig) is being developed for prophylaxis of ZIKV in at-risk populations, including women of childbearing potential and pregnant women. A phase 1 single-center, double-blind, randomized, placebo-controlled study was conducted to assess the safety and pharmacokinetics (PK) of a single 50.0-mL ZIKV-Ig intravenous dose in healthy adult male or non-pregnant female subjects 18 to 55 years of age. Subjects received either ZIKV-Ig (n = 19) or saline placebo (n = 11). Safety was evaluated based on adverse events (AEs), laboratory test results, physical examinations, and vital signs. Overall, there were 11 subjects (36.7%) with treatment-related AEs including eight subjects (42.1%) in the ZIKV-Ig group and three subjects (27.3%) in the placebo group. Of the AEs considered treatment related, three subjects (15.8%) experienced headache (mild). There were no serious AEs, no deaths, and no discontinuations resulting from AEs. Overall, the safety profile of ZIKV-Ig in this study population of healthy adult subjects appeared to be safe and well tolerated. The results of the pharmacokinetic analysis determined that ZIKV-Ig had a maximum observed concentration of 182.3 U/mL (coefficient of variation, 21.3%), the time at which Cmax occurred of 2.3 hours ± 1.0 (SD), an area under the concentration-time curve0-∞ of 77,224 h × U/mL (coefficient of variation, 17.9%), and a half-life of 28.1 days, which is similar to other human-derived commercial Ig intravenous products.