• Kassoum Kayentao, Aissata Ongoiba, Anne C Preston, Sara A Healy, Zonghui Hu, Jeff Skinner, Safiatou Doumbo, Jing Wang, Hamidou Cisse, Didier Doumtabe, Abdrahamane Traore, Hamadi Traore, Adama Djiguiba, Shanping Li, Mary E Peterson, Shinyi Telscher, Azza H Idris, William C Adams, Adrian B McDermott, Sandeep Narpala, Bob C Lin, Leonid Serebryannyy, Somia P Hickman, Andrew J McDougal, Sandra Vazquez, Matthew Reiber, Judy A Stein, Jason G Gall, Kevin Carlton, Philipp Schwabl, Siriman Traore, Mamadou Keita, Amatigué Zéguimé, Adama Ouattara, M'Bouye Doucoure, Amagana Dolo, Sean C Murphy, Daniel E Neafsey, Silvia Portugal, 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 of 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, M.K., A.Z., A. Ouattara, M.D., A. Dolo, A. Djimdé, B.T.); the Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, Division of Intramural Research (A.C.P., S.A.H., J.S., H.C., S.L., M.E.P., P.D.C.), and the Biostatistics Research Branch, Division of Clinical Research (Z.H.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, the Vaccine Research Center (S. Telscher, A.H.I., W.C.A., A.B.M., S.N., B.C.L., L.S., S.P.H., A.J.M., S.V., M.R., J.A.S., J.G.G., K.C., R.A.S.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick (J.W.) - all in Maryland; the Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston (P.S., D.E.N.); the Malaria Molecular Diagnostic Laboratory, Department of Laboratory Medicine and Pathology, and the Center for Emerging and Re-emerging Infectious Diseases, University of Washington, Seattle (S.C.M.); and the Max Planck Institute for Infection Biology, Berlin (S.P.).
• N. Engl. J. Med. 2024 May 2; 390 (17): 154915591549-1559.

BackgroundSubcutaneous administration of the monoclonal antibody L9LS protected adults against controlled Plasmodium falciparum infection in a phase 1 trial. Whether a monoclonal antibody administered subcutaneously can protect children from P. falciparum infection in a region where this organism is endemic is unclear.MethodsWe conducted a phase 2 trial in Mali to assess the safety and efficacy of subcutaneous administration of L9LS in children 6 to 10 years of age over a 6-month malaria season. In part A of the trial, safety was assessed at three dose levels in adults, followed by assessment at two dose levels in children. In part B of the trial, children were randomly assigned, in a 1:1:1 ratio, to receive 150 mg of L9LS, 300 mg of L9LS, or placebo. The primary efficacy end point, assessed in a time-to-event analysis, was the first P. falciparum infection, as detected on blood smear performed at least every 2 weeks for 24 weeks. A secondary efficacy end point was the first episode of clinical malaria, as assessed in a time-to-event analysis.ResultsNo safety concerns were identified in the dose-escalation part of the trial (part A). In part B, 225 children underwent randomization, with 75 children assigned to each group. No safety concerns were identified in part B. P. falciparum infection occurred in 36 participants (48%) in the 150-mg group, in 30 (40%) in the 300-mg group, and in 61 (81%) in the placebo group. The efficacy of L9LS against P. falciparum infection, as compared with placebo, was 66% (adjusted confidence interval [95% CI], 45 to 79) with the 150-mg dose and 70% (adjusted 95% CI, 50 to 82) with the 300-mg dose (P<0.001 for both comparisons). Efficacy against clinical malaria was 67% (adjusted 95% CI, 39 to 82) with the 150-mg dose and 77% (adjusted 95% CI, 55 to 89) with the 300-mg dose (P<0.001 for both comparisons).ConclusionsSubcutaneous administration of L9LS to children was protective against P. falciparum infection and clinical malaria over a period of 6 months. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT05304611.).Copyright © 2024 Massachusetts Medical Society.

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