The National Institutes of Health Clinical Center in Bethesda, Maryland, has begun the phase 1 clinical trial for testing the effectiveness and safety of a monoclonal antibody against malaria, enrolling healthy adult volunteers. Its the first time mAb CIS43LS is being tested in humans.
The trial will be carried out in 73 volunteers aged between 18 and 50 years who never had malaria in their whole life. To evaluate the ability of mAb, most of the volunteers will be exposed to mosquitos carrying malaria parasite in controlled conditions at the Walter Reed National Military Medical Center in Bethesda.
This monoclonal antibody could be used by medical workers, military personals, and tourists who travel to regions where malaria is common once it is proven effective and safe. This single-dose monoclonal antibody could be valuable in preventing malaria infections for several months in certain parts of Africa, where malaria cases increase during the annual rainy seasons.
Several years ago, an antibody (CIS43) was isolated by Robert Seder, M.D., and colleagues at NIAID’s Vaccine Research Center (VRC) from the blood of a volunteer who obtained vaccine against Malaria. Researchers tested this isolated antibody in two different mouse models and found CIS43 to be highly effective in preventing malaria infection by the parasite Plasmodium falciparum. They published their findings in 2018.
Modifications were made to CIS43 to yield a more long-lasting mAb CIS43LS antibody. NIAID-funded Vaccine Clinical Material Program of Leidos Biomedical Research and VRC’s investigational product Vaccine Production Program, under a contract to the National Cancer Institute’s Frederick National Laboratory for Cancer Research, manufactured CIS43LS for clinical use.
In the clinical trial, a group of volunteers will receive a single dose of 5 milligrams per kilogram (mg/kg) of body weight CIS43LS as an injection under the skin, while other groups will receive a series of escalating dosages (5, 20, or 40 mg/kg of body weight) in a single dose intravenously.
Most of the volunteers will then be exposed to controlled malaria infection (P. falciparum 3D7) via mosquito bites anytime between the next ten days to 10 weeks. The infection is readily curable with two stranded anti-malarial medications.
During the first clinical trial of malaria antibody, the volunteers will be closely monitored using the most sensitive detection test for malaria so that any volunteer who is infected can be immediately treated even before the symptoms appear. Those volunteers who did not develop infection also will receive anti-malarial medication after 28 days of the challenge.
The scientists will also determine the optimum level dosage level of the drug required to prevent infection using the data collected about the level of mAB in blood, said the trial’s principal investigator, VRC scientist Martin Gaudinski, M.D.
Additional information about the study is available at clinicaltrials.gov using the identifier NCT04206332. Anyone who wishes to participate in the trial can call 301-402-8604 to learn more.