Kundu Prosenjit, Quinn Mark, Thomas Elaine, Christensen Jared C, Toussi Sima S, Alami Negar Niki, Banerjee Anindita
Pfizer Inc., Cambridge, MA, USA.
Pfizer Ltd, London, UK.
EBioMedicine. 2025 May 29;117:105765. doi: 10.1016/j.ebiom.2025.105765.
Human infection challenge studies (HICs) are powerful in establishing early proof-of-concept for experimental drugs and understanding disease pathogenesis. A comprehensive assessment of HICs will allow to understand the viral load (VL) dynamics and symptom score kinetics of respiratory syncytial virus (RSV) and facilitate drug development for RSV.
In this study, we conducted a systematic search of double-blind, placebo-controlled RSV HICs using Biosis Previews, Embase, Ovid MEDLINE, PubMed, ClinicalTrials.gov, and EudraCT from 1990 to August 2023. We estimated VL and symptom related measures in placebo and relative mean reduction (RMR) of the measures in the experimental drug compared to placebo. The primary outcomes are RMR of VL area under curve (AUC) and RMR of total symptom score (TSS) AUC, and the secondary outcomes are mean placebo VL AUC, mean placebo VL at peak, time to mean placebo peak VL, mean placebo TSS AUC, and time to mean placebo peak TSS. We used random-effects meta-analysis, except for time to mean peak VL and time to mean peak TSS, where descriptive statistics were summarised.
Number of studies varied across measures, from 4 (144 subjects in total) to 7 (247 subjects in total). Overall, relative mean reductions of 54% (95% CI: 32%-76%, I = 91%) and 76% (95% CI: 61%-91%, I = 21%) are observed in VL AUC and TSS AUC, respectively.
Assessment based on our primary outcomes showed, on average, a 54% reduction in VL AUC with significant heterogeneity between these studies. In contrast, the TSS AUC showed a greater average reduction of 76%, with much lower heterogeneity indicating more consistent results across studies for this measure. Our findings inform researchers on disease course and VL kinetics, critical data needed for designing RSV treatment studies and understanding implications in clinical practice.
This study was supported by Pfizer Inc.
人体感染挑战研究（HICs）在为实验药物建立早期概念验证以及理解疾病发病机制方面具有强大作用。对人体感染挑战研究进行全面评估将有助于了解呼吸道合胞病毒（RSV）的病毒载量（VL）动态和症状评分动力学，并促进RSV药物的开发。
在本研究中，我们使用Biosis Previews、Embase、Ovid MEDLINE、PubMed、ClinicalTrials.gov和EudraCT对1990年至2023年8月期间的双盲、安慰剂对照RSV人体感染挑战研究进行了系统检索。我们估计了安慰剂组的病毒载量及与症状相关的指标，以及实验药物组相对于安慰剂组这些指标的相对平均降低率（RMR）。主要结局为病毒载量曲线下面积（AUC）的相对平均降低率和总症状评分（TSS）AUC的相对平均降低率，次要结局为安慰剂组病毒载量AUC均值、安慰剂组病毒载量峰值时的均值、达到安慰剂组病毒载量峰值均值的时间、安慰剂组总症状评分AUC均值以及达到安慰剂组总症状评分峰值均值的时间。除达到病毒载量峰值均值的时间和达到总症状评分峰值均值的时间采用描述性统计汇总外，我们使用随机效应荟萃分析。
各项指标的研究数量有所不同，从4项（共144名受试者）到7项（共247名受试者）不等。总体而言，病毒载量AUC和总症状评分AUC的相对平均降低率分别为54%（95%CI：32%-76%，I² = 91%）和76%（95%CI：61%-91%，I² = 21%）。
基于我们的主要结局进行的评估显示，病毒载量AUC平均降低了54%，这些研究之间存在显著异质性。相比之下，总症状评分AUC平均降低幅度更大，为76%，异质性低得多，表明该指标在各项研究中的结果更为一致。我们的研究结果为研究人员提供了有关疾病进程和病毒载量动力学的信息，这是设计RSV治疗研究以及理解临床实践意义所需的关键数据。
本研究由辉瑞公司资助。
