1. The monoclonal antibody CIS43LS was associated with dose-dependent protection against malaria infection in adults in Mali.
2. CIS43LS had an acceptable adverse event profile, with headaches being the most common.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Malaria is a mosquito-transmitted disease, most commonly caused by the Plasmodium falciparum parasite, that affects between 200 million to 400 million people, causing more than 500,000 deaths annually. Although strategies such as insecticide-treated nets, artemisinin-based therapies and chemoprevention have been successful in the past, progress has stalled due to emergence of resistant mosquitos and parasites. Vaccines developed thus far have showed limited efficacy. CIS43LS is a monoclonal antibody developed to target a conserved epitope on P. falciparum surface protein. The current study was a phase 2 trial to assess the efficacy and safety of CIS43LS against P. falciparum in Mali during a rainy season. After 24 weeks, both the 10mg/kg and 40mg/kg doses of CIS43LS conferred significant protection against P. falciparum infections compared to placebo. Adverse events were all mild to moderate and, except headache, reported at similar rates across all the study groups. The study included only healthy adults in Mali. Therefore, further investigation will be needed in children and pregnant women, who are most vulnerable to severe malaria. Nevertheless, it provided early evidence that CIS43LS could complement current strategies in combating malaria.
Relevant Reading: A Monoclonal Antibody for Malaria Prevention
In-Depth [randomized controlled trial]: This was a two-part phase two trial to evaluate the safety and efficacy of CIS43LS in protecting against P. falciparum infection among healthy adults in Mali over a rainy season. Part A was an open-label dose-escalation study to assess the safety of CIS43LS at 5mg/kg, 10mg/kg, and 40mg/kg intravenous doses, where 18 participants were given the lowest dose, followed by a dose increase seven days after if no safety concerns occurred. Part B was a randomized placebo-controlled trial, where 330 participants were randomized 1:1:1 to receive an infusion of CIS43LS at 10mg/kg or 40mg/kg, or placebo. The primary efficacy outcome was P. falciparum infection as confirmed with blood smears by 24 weeks. In Part A, solicited local and systemic adverse events from CIS43LS were all mild in severity. In Part B, P. falciparum infections were detected in 35.5% of participants who were given 10mg/kg of CIS43LS, 18.2% of those given 40mg/kg CIS43LS, and 78.2% of placebo recipients. This translated to an efficacy of 88.2% for 40mg/kg CIS43LS (adjusted 95% confidence interval [CI], 79.3 to 93.3; p<0.001) and 75.0% for the 10mg/kg dose (adjusted 95% CI, 61.0 to 84.0; p<0.001), compared to placebo. When compared to placebo, solicited local and systemic adverse events within seven days after study drug administration were all mild to moderate and reported at similar rates across both CIS43LS doses and placebo, except for moderate headache, which was 3.3 times more common with the 40mg/kg CIS43LS dose compared to placebo. These results provided early evidence that monoclonal antibodies such as CIS43LS can serve as effective complements to current strategies to protect against malaria.
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