美国国立卫生研究院Robert A. Seder团队研究了马里抗疟疾单克隆抗体的安全性和有效性。相关论文于2022年10月31日发表在《新英格兰医学杂志》上。

CIS43LS是一种单克隆抗体，在1期临床试验中显示其可预防恶性疟原虫感染。单克隆抗体能否在恶性疟原虫感染流行的地区预防该感染尚不得而知。

研究组进行了一项2期临床试验，以评估在6个月的疟疾季中，单次静脉输注CIS43LS对马里健康成年人恶性疟原虫感染的安全性和有效性。A部分中，研究组在三个递增剂量水平下评估了安全性。B部分中，参与者被随机分配（比例为1:1:1），每千克体重接受10毫克CIS43LS、40毫克CIS43 LS或安慰剂。

在事件时间分析中评估的主要疗效终点是血液涂片检查中检测到的首次恶性疟原虫感染，该检查至少每2周进行一次，持续24周。在入组时，所有参与者都接受了蒿甲醚-羽扇豆碱以清除可能的恶性疟原虫感染。

在B部分，330名成年人接受了随机分组；110人被分配到每个试验组。40毫克CIS43LS组的中度头痛风险是安慰剂组的3.3倍。10毫克CIS43LS组中有39名参与者（35.5%）在血液涂片检查中检测到恶性疟原虫感染，40毫克CIS43ALS组中有20名参与者（18.2%），安慰剂组中有86名参与者（78.2%）。6个月时，40毫克CIS43LS组与安慰剂组相比疗效为88.2%，10毫克CIS43LS组与安慰剂组相比疗效为75.0%。

研究结果表明，在马里6个月的疟疾季节，CIS43LS对恶性疟原虫感染具有保护作用，且没有明显的安全问题。

附：英文原文

Title: Safety and Efficacy of a Monoclonal Antibody against Malaria in Mali | NEJM

Author: Kassoum Kayentao, M.D., Ph.D., M.P.H.,, Aissata Ongoiba, M.D., M.P.H.,, Anne C. Preston, R.N.,, Sara A. Healy, M.D., M.P.H.,, Safiatou Doumbo, M.D., Ph.D.,, Didier Doumtabe, Pharm.D.,, Abdrahamane Traore, M.D.,, Hamadi Traore, M.D.,, Adama Djiguiba, M.D.,, Shanping Li, M.S.,, Mary E. Peterson, B.S.,, Shinyi Telscher, Pharm.D.,, Azza H. Idris, M.D.,, Neville K. Kisalu, Ph.D.,, Kevin Carlton, M.S.,, Leonid Serebryannyy, Ph.D.,, Sandeep Narpala, Ph.D.,, Adrian B. McDermott, Ph.D.,, Martin Gaudinski, M.D.,, Siriman Traore, M.S.,, Hamidou Cisse, Pharm.D.,, Mamadou Keita, Pharm.D.,, Jeff Skinner, M.S.,, Zonghui Hu, Ph.D.,, Amatigué Zéguimé, Pharm.D.,, Adama Ouattara, Pharm.D.,, M’Bouye Doucoure, M.S.,, Amagana Dolo, Pharm.D.,, Abdoulaye Djimdé, Pharm.D., Ph.D.,, Boubacar Traore, Pharm.D., Ph.D.,, Robert A. Seder, M.D.,, and Peter D. Crompton, M.D., M.P.H.

Issue&Volume: 2022-10-31

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.

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.

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).

Conclusions

CIS43LS was protective against P. falciparum infection over a 6-month malaria season in Mali without evident safety concerns.

DOI: 10.1056/NEJMoa2206966

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2206966