Safety, Tolerability, Pharmacokinetics, and Immunogenicity of mAb114: A Phase 1 Trial of a Therapeutic Monoclonal Antibody Targeting Ebola Virus Glycoprotein

Background: mAb114 is a single monoclonal antibody targeting the receptor binding domain of Ebola virus glycoprotein that prevents mortality in rhesus macaques treated after lethal challenge with Zaire ebolavirus. We present expedited data from a phase 1 study to evaluate mAb114 safety, tolerability, pharmacokinetics, and immunogenicity. Methods: VRC 608 is a phase 1, dose-escalation study performed at the National Institutes of Health (NIH) Clinical Center. Healthy adults ages 18-60 were sequentially enrolled into dose groups of 5, 25, and 50 mg/kg and infused intravenously (IV) with mAb114 over 30 minutes and followed for 24 weeks. Safety and tolerability were assessed through soliciting infusion site and systemic symptoms by self-reporting, direct clinician assessment, and clinical laboratory data. All participants have completed the 28 day adverse event reporting period and are currently either in Correspondence: Julie E. Ledgerwood, Phone: 301-594-8502, ledgerwood@mail.nih.gov. Contributors MRG is the principal investigator of VRC 608. AW, CC, LAH, GLC, JEL were study investigators. MN and EC did the statistical analysis. MRG, JM, EB, SS, LN, LAH, IJG, NB, GLC, CL, FA, GY, JG, KC, HL, AM, RTB, EC, JRM, BSG, RK, NJS, and JEL designed the clinical trial. MRG, CC, LN, LAH, and IJG collected data. MRG, EEC, KVH, JM, CC, AW, LAH, EB, LN, IJG, GY, GLC, MN, SS, and NB analyzed and interpreted data. All authors contributed to the writing of the report and approved the final version. Registration: clinicaltrials.gov NCT03478891 Declaration of Interests NJS, JEL, and BSG are listed as inventors on pending patent applications for mAb114 which has been non-exclusively licensed. All other authors have no conflicts of interest. HHS Public Access Author manuscript Lancet. Author manuscript; available in PMC 2020 March 02. Published in final edited form as: Lancet. 2019 March 02; 393(10174): 889–898. doi:10.1016/S0140-6736(19)30036-4. A uhor M anscript