• Kassoum Kayentao, Aissata Ongoiba, Anne C Preston, Sara A Healy, Safiatou Doumbo, Didier Doumtabe, Abdrahamane Traore, Hamadi Traore, Adama Djiguiba, Shanping Li, Mary E Peterson, Shinyi Telscher, Azza H Idris, Neville K Kisalu, Kevin Carlton, Leonid Serebryannyy, Sandeep Narpala, Adrian B McDermott, Martin Gaudinski, Siriman Traore, Hamidou Cisse, Mamadou Keita, Jeff Skinner, Zonghui Hu, Amatigué Zéguimé, Adama Ouattara, M'Bouye Doucoure, Amagana Dolo, Abdoulaye Djimdé, Boubacar Traore, Robert A Seder, Peter D Crompton, and Mali Malaria mAb Trial Team.
• From the Malaria Research and Training Center, Mali International Center for Excellence in Research, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali (K.K., A. Ongoiba, S.D., D.D., A.T., H.T., A. Djiguiba, S. Traore, H.C., M.K., A.Z., A. Ouattara, M.D., A. Dolo, A. Djimdé, B.T.); and the Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, Division of Intramural Research (A.C.P., S.A.H., S.L., M.E.P., J.S., P.D.C.), and the Biostatistics Research Branch, Division of Clinical Research (Z.H.), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Rockville, and the Vaccine Research Center, NIAID, NIH, Bethesda (S. Telscher, A.H.I., N.K.K., K.C., L.S., S.N., A.B.M., M.G., R.A.S.) - all in Maryland.
• N. Engl. J. Med. 2022 Nov 17; 387 (20): 183318421833-1842.

BackgroundCIS43LS is a monoclonal antibody that was shown to protect against controlled Plasmodium falciparum infection in a phase 1 clinical trial. Whether a monoclonal antibody can prevent P. falciparum infection in a region in which the infection is endemic is unknown.MethodsWe conducted a phase 2 trial to assess the safety and efficacy of a single intravenous infusion of CIS43LS against P. falciparum infection in healthy adults in Mali over a 6-month malaria season. In Part A, safety was assessed at three escalating dose levels. In Part B, participants were randomly assigned (in a 1:1:1 ratio) to receive 10 mg of CIS43LS per kilogram of body weight, 40 mg of CIS43LS per kilogram, or placebo. The primary efficacy end point, assessed in a time-to-event analysis, was the first P. falciparum infection detected on blood-smear examination, which was performed at least every 2 weeks for 24 weeks. At enrollment, all the participants received artemether-lumefantrine to clear possible P. falciparum infection.ResultsIn Part B, 330 adults underwent randomization; 110 were assigned to each trial group. The risk of moderate headache was 3.3 times as high with 40 mg of CIS43LS per kilogram as with placebo. P. falciparum infections were detected on blood-smear examination in 39 participants (35.5%) who received 10 mg of CIS43LS per kilogram, 20 (18.2%) who received 40 mg of CIS43LS per kilogram, and 86 (78.2%) who received placebo. At 6 months, the efficacy of 40 mg of CIS43LS per kilogram as compared with placebo was 88.2% (adjusted 95% confidence interval [CI], 79.3 to 93.3; P<0.001), and the efficacy of 10 mg of CIS43LS per kilogram as compared with placebo was 75.0% (adjusted 95% CI, 61.0 to 84.0; P<0.001).ConclusionsCIS43LS was protective against P. falciparum infection over a 6-month malaria season in Mali without evident safety concerns. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04329104.).Copyright © 2022 Massachusetts Medical Society.

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