Safety and Efficacy of a Monoclonal Antibody against Malaria in Mali.
Safety and Efficacy of a Monoclonal Antibody against Malaria in Mali.
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DOI：
10.1056/nejmoa2206966
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发表时间：
2022-11-17
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CIS 43 LS是一种单克隆抗体，在1期临床试验中显示可保护免受受控恶性疟原虫感染。单克隆抗体是否能在恶性疟原虫感染流行的地区预防恶性疟原虫感染尚不清楚。我们进行了一项2期试验，以评估在马里健康成年人中单次静脉输注CIS 43 LS在6个月疟疾季节中对抗恶性疟原虫感染的安全性和有效性。在A部分中，在三个递增剂量水平下评估安全性。在B部分，参与者被随机分配（以1：1：1的比例）接受每公斤体重10 mg的CIS 43 LS，每公斤40 mg的CIS 43 LS或安慰剂。主要疗效终点，在时间-事件分析中进行评估，是在血涂片检查中首次检测到恶性疟原虫感染，至少每2周进行一次，持续24周。在招募时，所有参与者都接受了蒿甲醚-苯芴醇以清除可能的恶性疟原虫感染。在B部分，330名成人接受随机化; 110名被分配到每个试验组。中度头痛的风险是安慰剂组的3.3倍。在39名（35.5%）接受每公斤10 mg CIS 43 LS的参与者、20名（18.2%）接受每公斤40 mg CIS 43 LS的参与者和86名（78.2%）接受安慰剂的参与者中，在血液涂片检查中检测到恶性疟原虫感染。在6个月时，与安慰剂相比，每公斤40 mg CIS 43 LS的疗效为88.2%（调整后的95%置信区间[CI]，79.3至93.3; P<0.001），每公斤10 mg CIS 43 LS与安慰剂相比的疗效为75.0%（调整后的95% CI，61.0至84.0; P<0.001）。在马里，CIS 43 LS在6个月的疟疾季节内对恶性疟原虫感染具有保护作用，没有明显的安全性问题。（由国家过敏和传染病研究所资助; ClinicalTrials.gov编号，NCT 04329104。
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. 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. 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). 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.)