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Safety and Efficacy of a Monoclonal Antibody against Malaria in Mali.
- Source :
-
The New England journal of medicine [N Engl J Med] 2022 Nov 17; Vol. 387 (20), pp. 1833-1842. Date of Electronic Publication: 2022 Oct 31. - Publication Year :
- 2022
-
Abstract
- Background: CIS43LS 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.<br />Methods: We 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.<br />Results: 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. 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).<br />Conclusions: CIS43LS 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.).<br /> (Copyright © 2022 Massachusetts Medical Society.)
- Subjects :
- Adult
Humans
Artemether, Lumefantrine Drug Combination therapeutic use
Mali
Plasmodium falciparum
Headache chemically induced
Antimalarials adverse effects
Antimalarials therapeutic use
Malaria, Falciparum diagnosis
Malaria, Falciparum drug therapy
Malaria, Falciparum prevention & control
Antibodies, Monoclonal, Humanized adverse effects
Antibodies, Monoclonal, Humanized therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1533-4406
- Volume :
- 387
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- The New England journal of medicine
- Publication Type :
- Academic Journal
- Accession number :
- 36317783
- Full Text :
- https://doi.org/10.1056/NEJMoa2206966