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治疗性抗黄热病毒人源抗体1期临床试验效果分析
2020-08-01 23:17

分析新加坡-麻省理工学院研究与技术联盟Eng-Eong Ooi团队研究了治疗性抗黄热病毒人源抗体临床1期试验的效果。2020年7月30日,该研究发表在《新英格兰医学杂志》上。

黄热病出现于撒哈拉以南非洲和南美洲,疫苗剂量不足和缺乏治疗药物将使其危及全球健康。

在1a期临床试验中,研究组评估了TY014(一种完全人源IgG1抗黄热病毒单克隆抗体)的安全性、副作用和药代动力学。在一项双盲、1b期临床试验中,研究组评估了TY014与安慰剂相比,消除与活黄热病疫苗(YF17D-204; Stamaril)相关病毒血症的疗效。主要安全结局是输注1小时后以及整个试验中报告的不良事件。

在临床1a期共有27名健康参与者,在临床1b期共有10名参与者。在临床1a期,有22位参与了TY014剂量递增至每公斤体重最大20毫克的试验。在临床1a和1b期试验中,TY014组的27位参与者中有1位在输注后1小时内发生了不良事件,而安慰剂组的10位参与者中则没有。在整个试验期间,TY014组的22位参与者和安慰剂组的8位参与者中分别至少发生了一次不良事件。

TY014的平均半衰期约为12.8天。在输注后48小时,接受2 mg/kg的TY014起始剂量的5名受试者中,没有一人出现YF17D-204病毒血症;这些受试者在整个试验过程中均保持无病毒血症。5名接受安慰剂的受试者中有2名在输液后48小时观察到病毒血症,另外2名接受安慰剂的受试者在72小时后观察到病毒血症。与安慰剂组相比,TY014组与黄热病疫苗相关症状的发生率较低。

综上,TY014的1期临床试验安全性好,有潜在临床益处,但仍需在2期临床试验中进一步评估。

附:英文原文

Title: Phase 1 Trial of a Therapeutic Anti–Yellow Fever Virus Human Antibody

Author: Jenny G. Low, M.R.C.P., M.P.H.,, Justin H.J. Ng, Ph.D.,, Eugenia Z. Ong, Ph.D.,, Shirin Kalimuddin, M.R.C.P., M.P.H.,, Limin Wijaya, M.R.C.P.,, Yvonne F.Z. Chan, M.R.C.P.,, Dorothy H.L. Ng, M.B., Ph.D.,, Hwee-Cheng Tan,, Anjali Baglody, M.Sc.,, Yok-Hian Chionh, Ph.D.,, Debbie C.P. Lee, Ph.D.,, Yadunanda Budigi, Ph.D.,, Ram Sasisekharan, Ph.D.,, and Eng-Eong Ooi, B.M., B.S., Ph.D.

Issue&Volume: 2020-07-29

Abstract: Abstract

Background

Insufficient vaccine doses and the lack of therapeutic agents for yellow fever put global health at risk, should this virus emerge from sub-Saharan Africa and South America.

Methods

In phase 1a of this clinical trial, we assessed the safety, side-effect profile, and pharmacokinetics of TY014, a fully human IgG1 anti–yellow fever virus monoclonal antibody. In a double-blind, phase 1b clinical trial, we assessed the efficacy of TY014, as compared with placebo, in abrogating viremia related to the administration of live yellow fever vaccine (YF17D-204; Stamaril). The primary safety outcomes were adverse events reported 1 hour after the infusion and throughout the trial. The primary efficacy outcome was the dose of TY014 at which 100% of the participants tested negative for viremia within 48 hours after infusion.

Results

A total of 27 healthy participants were enrolled in phase 1a, and 10 participants in phase 1b. During phase 1a, TY014 dose escalation to a maximum of 20 mg per kilogram of body weight occurred in 22 participants. During phases 1a and 1b, adverse events within 1 hour after infusion occurred in 1 of 27 participants who received TY014 and in none of the 10 participants who received placebo. At least one adverse event occurred during the trial in 22 participants who received TY014 and in 8 who received placebo. The mean half-life of TY014 was approximately 12.8 days. At 48 hours after the infusion, none of the 5 participants who received the starting dose of TY014 of 2 mg per kilogram had detectable YF17D-204 viremia; these participants remained aviremic throughout the trial. Viremia was observed at 48 hours after the infusion in 2 of 5 participants who received placebo and at 72 hours in 2 more placebo recipients. Symptoms associated with yellow fever vaccine were less frequent in the TY014 group than in the placebo group.

Conclusions

This phase 1 trial of TY014 did not identify worrisome safety signals and suggested potential clinical benefit, which requires further assessment in a phase 2 trial.

DOI: NJ202007303830512

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2000226

 

The New England Journal of Medicine:《新英格兰医学杂志》,创刊于1812年。隶属于美国麻省医学协会,最新IF:70.67
官方网址:http://www.nejm.org/
投稿链接:http://www.nejm.org/page/author-center/home


本期文章:《新英格兰医学杂志》:Vol.383 No.5

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