本文由小咖机器人翻译整理

期刊来源：N Engl J Med

原文链接：https://doi.org/10.1056/NEJMoa2312775

摘要内容如下：

背景

在一项1期临床试验中，单克隆抗体L9LS皮下注射可保护成人免受恶性疟原虫感染。在恶性疟原虫流行的地区，皮下注射单克隆抗体是否可以保护儿童免受恶性疟原虫感染尚不清楚。

方法

我们在马里进行了一项2期临床试验，以评估6至10岁儿童在为期6个月的疟疾季节中皮下注射L9LS的安全性和有效性。在试验的A部分中，在成人中评估了三个剂量水平的安全性，随后在儿童中评估了两个剂量水平的安全性。在试验的B部分中，儿童以1:1:1的比例被随机分配接受150 mg的L9LS、300 mg的L9LS或安慰剂。在时间-事件分析中评估的主要疗效终点是首次恶性疟原虫感染，至少每2周进行一次血涂片检测，持续24周。次要疗效终点是临床疟疾的首次发作，这是在时间-事件分析中评估的。

结果

在试验的剂量递增部分（A部分）中未发现安全性问题。在B部分中，225名儿童接受了随机分组，每组75名儿童。150毫克组中有36名参与者（48%）、300毫克组中有30名参与者（40%）、安慰剂组中有61名参与者（81%）感染了恶性疟原虫，在部分B.恶性疟原虫感染中没有发现安全性问题。与安慰剂相比，150mg剂量的L9LS对恶性疟原虫感染的疗效为66%（调整后的置信区间[95%CI]，45-79），300mg剂量的L9LS的疗效为70%（调整后的95%CI，50-82）（两组比较P<0.001）。150 mg剂量对临床疟疾的疗效为67%（调整后95%CI为39至82），300 mg剂量为77%（调整后95%CI为55至89）（两组比较P<0.001）。

结论

在6个月的时间内，对儿童皮下注射L9LS对恶性疟原虫感染和临床疟疾具有保护作用。（由国家过敏和传染病研究所资助；ClinicalTrials.gov编号，NCT05304611。）

英文原文如下：

Abstracts

BACKGROUND  Subcutaneous administration of the monoclonal antibody L9LS protected adults against controlled Plasmodium falciparum infection in a phase 1 trial. Whether a monoclonal antibody administered subcutaneously can protect children from P. falciparum infection in a region where this organism is endemic is unclear.

METHODS  We conducted a phase 2 trial in Mali to assess the safety and efficacy of subcutaneous administration of L9LS in children 6 to 10 years of age over a 6-month malaria season. In part A of the trial, safety was assessed at three dose levels in adults, followed by assessment at two dose levels in children. In part B of the trial, children were randomly assigned, in a 1:1:1 ratio, to receive 150 mg of L9LS, 300 mg of L9LS, or placebo. The primary efficacy end point, assessed in a time-to-event analysis, was the first P. falciparum infection, as detected on blood smear performed at least every 2 weeks for 24 weeks. A secondary efficacy end point was the first episode of clinical malaria, as assessed in a time-to-event analysis.

RESULTS  No safety concerns were identified in the dose-escalation part of the trial (part A). In part B, 225 children underwent randomization, with 75 children assigned to each group. No safety concerns were identified in part B. P. falciparum infection occurred in 36 participants (48%) in the 150-mg group, in 30 (40%) in the 300-mg group, and in 61 (81%) in the placebo group. The efficacy of L9LS against P. falciparum infection, as compared with placebo, was 66% (adjusted confidence interval [95% CI], 45 to 79) with the 150-mg dose and 70% (adjusted 95% CI, 50 to 82) with the 300-mg dose (P<0.001 for both comparisons). Efficacy against clinical malaria was 67% (adjusted 95% CI, 39 to 82) with the 150-mg dose and 77% (adjusted 95% CI, 55 to 89) with the 300-mg dose (P<0.001 for both comparisons).

CONCLUSIONS  Subcutaneous administration of L9LS to children was protective against P. falciparum infection and clinical malaria over a period of 6 months. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT05304611.).

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