Safety, tolerability, pharmacokinetics, and immunogenicity of the therapeutic monoclonal antibody mAb114 targeting Ebola virus glycoprotein (VRC 608): an open-label phase 1 study

Abstract

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. 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 long-term follow up or have completed study visits. The primary study outcome was safety and tolerability, with pharmacokinetic and anti-drug antibody evaluation as secondary objectives. Nineteen participants were enrolled between May 16, 2018, and September 27, 2018. One participant was not infused because intravenous access was not adequate. Eighteen participants received a single infusion of 5 mg/kg (n=3), 25 mg/kg (n=5), or 50 mg/kg (n=10) of mAb114. All infusions were well tolerated at infusion rates between 209-375 mL per hour over 30-37 minutes with zero infusion reactions or rate adjustments. No participants had infusion site symptoms. Systemic symptoms were all mild and present only in 22% of participants across all dosing groups. There were no unsolicited adverse events (AEs) related to mAb114 and one serious adverse event (SAE) unrelated to mAb114. mAb114 has linear pharmacokinetics and a half-life of approximately 24 days with no evidence of anti-drug antibody development. mAb114 was well-tolerated, demonstrated linear pharmacokinetics, and was easily and rapidly infused making it an attractive and deployable option for treatment in outbreak settings. The VRC 608 clinical trial was supported by the intramural research program of the Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID), NIH. mAb114 production was funded by the Defense Advanced Research Projects Agency.