NIAID Sponsors Phase I Clinical Trial of mAb CIS43LS targeting Malaria

The National Institute of Allergy and Infectious Diseases (NIAID) has developed a monoclonal antibody (mAb) called mAb CIS43LS targeting malaria. They are now enrolling healthy adult volunteers in a Phase I clinical trial testing the safety and effectiveness of the investigational medicine at the National Institutes of Health Clinical Center in Bethesda, Maryland. After receiving mAb CIS43LS, most of the volunteers will be exposed to the malaria parasite-carrying mosquitos under carefully controlled conditions at the Walter Reed National Military Medical Center where investigators will assess the ability of the investigational treatment to confer protection from malaria infection.

Health Challenge

Currently, there is no highly effective, long-lasting vaccine to prevent malaria, the mosquito-spread disease responsible for about 430,000 deaths annually, primarily among young children in sub-Saharan Africa.

Developed by NIAID’s VRC Investigational Product Vaccine Production Program

Several years ago, Robert Seder, M.D., and colleagues at NIAID’s Vaccine Research Center (VRC) and support from Fred Hutchinson Cancer Research Center, isolated an antibody (CIS43) from the blood of a volunteer who had received an investigational vaccine made from whole, weakened malaria parasites. When tested in two different mouse models of malaria infection, CIS43 was highly effective at preventing infection by the deadliest malaria parasite, Plasmodium falciparumthe team reported in 2018. Modifications to CIS43 yielded mAb CIS43LS, which lasts longer in the blood than the original antibody. CIS43LS was manufactured for clinical use by the VRC’s investigational product Vaccine Production Program and the NIAID-funded Vaccine Clinical Material Program of Leidos Biomedical Research, Inc., under a contract to the National Cancer Institute’s Frederick National Laboratory for Cancer Research.

The Study

Titled “VRC 612: A Phase I, Dose Escalation, Open-Label Clinical Trial with Experimental Controlled Human Malaria Infections (CHMI) to Evaluate the Safety and Protective Efficacy of an Anti-Malaria Human Monoclonal Antibody, VRC-MALMAB0100-00-AB (CIS43LS), in Healthy, Malaria-Na(SqrRoot) ve Adults,” this study is the first one to test mAb CIS43LS in humans. The study sponsor aims to enroll up to 73 volunteers aged 18 though 50 years old who have never had malaria. After receiving mAb CIS43LS, most of the volunteers will be exposed to malaria parasite-carrying mosquitoes under carefully controlled conditions at the Walter Reed National Military Medical Center in Bethesda to assess the ability of the experimental product to confer protection from malaria infection. The study commenced January 2020 and will conclude December 2022. 

Lead Research/Investigator

Martin R. Gaudinski, MD, Medical Director at Vaccine Research Center Clinical Trials Program, NIAID, National Institutes of Health

Call to Action: Drug resistance possesses a growing problem in 21st-centruy malaria treatment. Resistance is now common against all classes of antimalarial drugs apart from artemisinin but the costs of these limit their use in the developing worldTrialSite News have covered several ongoing malaria research initiatives around the world, such as a University of Oxford-led team. The race is on to find a superior way to stop this killer for good in the equatorial world.