A single intravenous (IV) infusion of the monoclonal antibody (mAb) CIS43LS was found to be safe and conferred high protective efficacy against Plasmodium falciparum infection during a 6-month malaria season in Mali. These study findings were published in the New England Journal of Medicine.
Researchers conducted a phase 2 trial to assess whether mAb treatment with CIS43LS protects against P falciparum infection among healthy adults in Mali. The trial comprised 2 parts and was conducted during a 6-month malaria season. The first part of the trial assessed the safety of CIS43LS at 3 escalating dose levels. In the second part of the trial to assess the efficacy of CIS43LS, participants were randomly assigned in a 1:1:1 fashion to receive either CIS43LS at a dose of 10 mg/kg of body weight (group 1), CIS43LS at a dose of 40 mg/kg of body weight (group 2), or placebo (group 3). The primary efficacy endpoint was detection of the first P falciparum infection via blood-smear examination, evaluated in a time-to-event analysis. Blood-smear examinations were performed in 2-week intervals for 24 weeks, and all participants received artemether-lumefantrine at enrollment.
The final modified intention-to-treat efficacy analysis comprised 330 participants, of whom 110 were assigned to each of the 3 groups. Of participants in groups 1, 2, and 3, the median age was 34 (range, 18-54), 35 (range, 18-53), and 35 (range, 18-53) years; 46.4%, 42.7%, and 40.0% were women; and 13.6%, 8.2%, and 7.3% had plasmodium species detected on blood-smear examination at enrollment, respectively. Of note, the median time between administration of artemether-lumefantrine and CIS43LS or placebo was 9 days for all 3 participant groups.
Following administration of CIS43LS or placebo, results of blood-smear examination showed the onset of P falciparum infection between weeks 1 and 24 among 35.5% of participants in group 1, 18.2% of participants in group 2, and 78.2% of participants in group 3. Compared with placebo, the efficacy ([1-hazard ratio]×100) of 40 mg and 10 mg of CIS43LS was 88.2% (95% CI, 79.3-93.3; P <.001) and 75.0% (95% CI, 61.0-84.0; P <.001), respectively.
Between baseline and day 7, the rate of solicited local and systemic adverse events was similar across all 3 participant groups, with the exception of headache. Of note, all events were of mild to moderate severity. Moderate headache was significantly more common among patients who received 40 mg of CIS43LS vs placebo (11.8% vs 3.6%), indicating 40 mg of CIS43LS was associated with a 3.3-times (95% CI, 1.1-9.7) increased risk for moderate headache.
A total 1235 unsolicited AEs occurred among all participants by week 24, including 342 grade 1; 880 grade 2; 12 grade 3; and 1 grade 5 AE. There were 4 severe AEs reported, though none were determined to be related to treatment.
This study was limited by the inclusion of only healthy adults and the inability to determine factors associated with the occurrence of breakthrough infections.
“These results provide a foundation for considering several clinical-use cases for antimalarial monoclonal antibodies,” the researchers concluded.
Kayentao K, Ongoiba A, Preston AC, et al; on behalf of the Mali Malaria mAb Trial Team. Safety and efficacy of a monoclonal antibody against malaria in Mali. N Engl J Med. Published online October 31, 2022. doi:10.1056/NEJMoa2206966