Human monoclonal antibody mAb114, which has been used to treat Ebola patients as an investigational therapy in the current outbreak in the Democratic Republic of the Congo (DRC), was safe and well tolerated among adult volunteers in the U.S., an open-label phase I trial found.
Intravenous infusion was tolerated at the 5 mg/kg, 25 mg/kg, and 50 mg/kg doses, with no participants reporting infusion site symptoms or unsolicited adverse events, reported Martin R. Gaudinski, MD, of the VRC 608 Study team at the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, and colleagues.
Moreover, the drug had linear pharmacokinetics, and had no evidence of anti-drug antibody development, the authors wrote in The Lancet.
MAb114 has been used as one of several investigational therapies to treat Ebola patients in the DRC — both during this outbreak and the one in early 2018. An infectious challenge model showed promise in reversing viremia, clinical symptoms, and preventing death in non-human primates, the authors said.
This treatment is being used in the current outbreak, both under compassionate use and as part of a phase II/III clinical trial of multiple investigational treatments, the NIH said in a statement. Citing this trial, the study authors wrote, “As this manuscript went to press, this study was in long-term follow-up.”
“Now with these clinical studies that are well developed, we will be able to get some really nice data that will help inform clinicians and developers of new medical countermeasures, specifically both the extended access protocol here in the United States and the multi-national clinical trial,” Aneesh Mehta, MD, of Emory University School of Medicine in Atlanta, told MedPage Today in a video that commented in general on investigational therapies for treating Ebola.
To date, 54 people with Ebola have received mAb114, the authors said. A statement released on January 24 by the World Health Organization now puts the number of confirmed/probable Ebola cases in the DRC at 713, with 439 deaths (case fatality rate: 62%).
The researchers described this as “the first in-human phase I, open-label, dose-escalation” trial of mAb114, which took place at the NIH Clinical Center. Participants were healthy volunteers, ages 18-60. They were enrolled into three groups with three different doses of the therapy (5 mg/kg, 25 mg/kg, and 50 mg/kg), administered intravenously over 30 minutes. Participants were then followed for 24 weeks, and following interim safety assessments, some patients were enrolled into increased dosing groups, the authors said.
Overall, 18 patients completed the safety assessment. Three were assigned to the 5 mg/kg group, five to the 25 mg/kg group, and 10 to the 50 mg/kg group. Two patients were lost to follow-up 56 days following drug administration and one withdrew from the trial after 28 days, the authors said — adding, “all other participants remain in long-term follow-up.”
There were no infusion reactions, and no fevers associated with infusion at any point during the study, Gaudinski and co-authors noted. “Mild solicited systemic reactogenicity” was reported in four of 18 patients 3 days following administration. There were three reports of malaise, and two reports each of myalgia, headache, chills, nausea, and joint pain.
Eight patients reported 10 unsolicited adverse events judged to be unrelated to the therapy, and one had an unrelated serious adverse event (vomiting and syncope 84 days after drug administration).
Examining secondary outcomes, the authors said that the therapy had linear pharmacokinetics, with a half-life of 24.2 days.
Limitations to the data include the small number of individuals in the trial, although the authors said that ongoing and future trials hope to add additional data from mAb114 recipients in outbreak settings.
Gaudinski disclosed no conflicts of interest; three co-authors are listed as inventors on pending patent applications for mAb114 that has been non-exclusively licensed.