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

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  • 1 Emergent BioSolutions Inc., Gaithersburg, Maryland;
  • | 2 Emergent BioSolutions Canada Inc., Winnipeg, Manitoba, Canada

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.

Author Notes

Address correspondence to Jason S. Richardson, Emergent BioSolutions Canada Inc., 155 Innovation Dr. Winnipeg MB, Canada, R3T 5Y3. E-mail: jrichardson@ebsi.com

Financial support: This work was funded by Emergent BioSolutions Inc.

Disclosure: Anthrasil®, CNJ-016®, and any and all Emergent BioSolutions Inc. brands, products, services, and feature names, logos, and slogans are trademarks or registered trademarks of Emergent BioSolutions Inc. or its subsidiaries in the United States or other countries. All other brands, products, services, and feature names or trademarks are the property of their respective owners.

Authors’ addresses: Jane White, Emergent BioSolutions Inc., Gaithersburg, MD, E-mail: whitej@ebsi.com. Priya Tunga, Deborah M. Anderson, Ken Iledan, Tobi Loreth, Geraldine S. Parrera, Hugo Astacio, Bojan Drobic, and Jason S. Richardson, Emergent BioSolutions Canada Inc., Winnipeg, Manitoba, Canada, E-mails: tungap@ebsi.com, andersond@ebsi.com, iledank@ebsi.com, loretht@ebsi.com, gparrera@ebsi.com, hastacio@ebsi.com, bdrobic@ebsi.com, and jrichardson@ebsi.com.

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