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Subcutaneous Administration of a Monoclonal Antibody to Prevent Malaria

2024; Massachusetts Medical Society; Volume: 390; Issue: 17 Linguagem: Inglês

10.1056/nejmoa2312775

1533-4406

Kassoum Kayentao, Aissata Ongoïba, Anne C Preston, Sara A. Healy, Zonghui Hu, Jeff Skinner, Safiatou Doumbo, Jing Wang, Hamidou Cisse, Didier Doumtabé, Abdrahamane Traoré, Hamadi Traore, Adama Djiguiba, Shanping Li, Mary Peterson, Shinyi Telscher, Azza H. Idris, William C. Adams, Adrian B. McDermott, Sandeep Narpala, Bob C. Lin, Leonid Serebryannyy, Somia P. Hickman, Andrew McDougal, Sandra Vazquez, M.A. REIBER, Judy Stein, Jason G. Gall, Kevin Carlton, Philipp Schwabl, Siriman Traoré, Mamadou Keïta, Amatigué Zéguimé, Adama Ouattara, M’Bouye Doucoure, Amagana Dolo, Sean C. Murphy, Daniel E. Neafsey, Sílvia Portugal, Abdoulaye Djimdé, Boubacar Traoré, Robert A. Seder, Peter D. Crompton,

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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.)