Safety and Efficacy of a Monoclonal Antibody against Malaria in Mali.

Abstract

CIS43LS is a monoclonal antibody that was shown to protect against controlled <i>Plasmodium falciparum</i> infection in a phase 1 clinical trial. Whether a monoclonal antibody can prevent <i>P. falciparum</i> infection in a region in which the infection is endemic is unknown. We conducted a phase 2 trial to assess the safety and efficacy of a single intravenous infusion of CIS43LS against <i>P. falciparum</i> 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 <i>P. falciparum</i> 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 <i>P. falciparum</i> infection. In 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. <i>P. falciparum</i> 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). CIS43LS was protective against <i>P. falciparum</i> 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.).