In the Journals

Investigational Ebola treatment yields positive results in phase 1 trial

MAb114, an investigational Ebola treatment, is safe, well tolerated, and easy to administer, according to results from an early-stage clinical trial published in The Lancet.

“Outbreaks of Ebola virus disease have occurred with increasing frequency since the discovery of the virus in 1976. No medical countermeasures have been registered and populations in endemic regions remain vulnerable to future Ebola virus disease outbreaks,” Martin R. Gaudinski, MD, medical director at the National Institute of Allergy and Infectious Diseases’ Vaccine Research Center Clinical Trials Program, and colleagues wrote. “The lethal nature of acute Ebola virus disease has a substantial effect on the health of both individuals and communities. Immunotherapy with monoclonal antibodies has shown promise in experimental nonhuman primate models and has been used in past and current outbreaks of Ebola virus disease.”

According to researchers, mAb114 is a single monoclonal antibody that targets the receptor-binding domain of Ebola virus glycoprotein. The antibody was isolated from a survivor of the 1995 Ebola outbreak in Kikwit, Democratic Republic of the Congo (DRC), who still had antibodies 11 years after infection.

Researchers assessed mAb114 as a single-infusion regiment in healthy adults through a dose-escalation phase 1 study conducted at the NIH Clinical Center in Bethesda, Maryland. Between May 16 and Sept. 27, 2018, 19 healthy adults were enrolled into three dose groups (5 mb/kg, 25 mb/kg and 50 mb/kg) and given the drug intravenously over 30 minutes. They were then followed for 24 weeks so researchers could evaluate the treatment’s safety and tolerability and track adverse events.

According to researchers, at the end of the trial, results showed that all infusions were well tolerated, although four participants reported mild side effects including discomfort, muscle or joint paint, and nausea following the treatment.

“In this first-in-human phase 1 study, we found mAb114 to be safe and well tolerated after intravenous infusion, with a mean serum half-life of 24.2 days and low pharmacokinetic variability among study participants,” the authors concluded. “Furthermore, mAb114 was delivered rapidly without infusion reactions, lending itself to ease of use in Ebola treatment units compared with regimens that require multiple infusions and long infusion times.”

Currently, mAb114 is being used to treat patients with Ebola in the ongoing outbreak in the DRC that began in August. To date, a total of 713 Ebola cases — 664 confirmed and 49 probable — have been reported, leading to 439 deaths. On Aug. 10, the Ministry of Health and Ethics Committee approved the use of mAb114 in patients infected with Ebola. According to the study, 54 people have received mAb114. Although the data from the DRC outbreak have yet to be analyzed, researchers say mAb114 is safe for further use. – by Caitlyn Stulpin

Disclosures: The authors report no relevant financial disclosures.

MAb114, an investigational Ebola treatment, is safe, well tolerated, and easy to administer, according to results from an early-stage clinical trial published in The Lancet.

“Outbreaks of Ebola virus disease have occurred with increasing frequency since the discovery of the virus in 1976. No medical countermeasures have been registered and populations in endemic regions remain vulnerable to future Ebola virus disease outbreaks,” Martin R. Gaudinski, MD, medical director at the National Institute of Allergy and Infectious Diseases’ Vaccine Research Center Clinical Trials Program, and colleagues wrote. “The lethal nature of acute Ebola virus disease has a substantial effect on the health of both individuals and communities. Immunotherapy with monoclonal antibodies has shown promise in experimental nonhuman primate models and has been used in past and current outbreaks of Ebola virus disease.”

According to researchers, mAb114 is a single monoclonal antibody that targets the receptor-binding domain of Ebola virus glycoprotein. The antibody was isolated from a survivor of the 1995 Ebola outbreak in Kikwit, Democratic Republic of the Congo (DRC), who still had antibodies 11 years after infection.

Researchers assessed mAb114 as a single-infusion regiment in healthy adults through a dose-escalation phase 1 study conducted at the NIH Clinical Center in Bethesda, Maryland. Between May 16 and Sept. 27, 2018, 19 healthy adults were enrolled into three dose groups (5 mb/kg, 25 mb/kg and 50 mb/kg) and given the drug intravenously over 30 minutes. They were then followed for 24 weeks so researchers could evaluate the treatment’s safety and tolerability and track adverse events.

According to researchers, at the end of the trial, results showed that all infusions were well tolerated, although four participants reported mild side effects including discomfort, muscle or joint paint, and nausea following the treatment.

“In this first-in-human phase 1 study, we found mAb114 to be safe and well tolerated after intravenous infusion, with a mean serum half-life of 24.2 days and low pharmacokinetic variability among study participants,” the authors concluded. “Furthermore, mAb114 was delivered rapidly without infusion reactions, lending itself to ease of use in Ebola treatment units compared with regimens that require multiple infusions and long infusion times.”

Currently, mAb114 is being used to treat patients with Ebola in the ongoing outbreak in the DRC that began in August. To date, a total of 713 Ebola cases — 664 confirmed and 49 probable — have been reported, leading to 439 deaths. On Aug. 10, the Ministry of Health and Ethics Committee approved the use of mAb114 in patients infected with Ebola. According to the study, 54 people have received mAb114. Although the data from the DRC outbreak have yet to be analyzed, researchers say mAb114 is safe for further use. – by Caitlyn Stulpin

Disclosures: The authors report no relevant financial disclosures.