Safety and pharmacokinetics of VRC07-523LS administered via different routes and doses (HVTN 127/HPTN 087): A Phase I randomized clinical trial

作者：Stephen R. Walsh, Cynthia L. Gay, Shelly Karuna, Ollivier Hyrien, Timothy Skalland, Kenneth H. Mayer, Magdalena E. Sobieszczyk, Lindsey R. Baden, Paul Goepfert, Carlos del Rı́o, Guiseppe Pantaleo, P. Andrew, Carissa Karg, Zonglin He, Huiyin Lu, Carmen A. Paez, Jane Baumblatt, Laura Polakowski, Wairimu Chege, Maija Anderson, Sophie Janto, Xue Han, Yunda Huang, Julie B. Dumond, Margaret E. Ackerman, Adrian B. McDermott, Britta Flach, Estelle Piwowar‐Manning, Kelly E. Seaton, Georgia D. Tomaras, David C. Montefiori, Lúcio Gama, John R. Mascola, for the HVTN 127/HPTN 087 Study Team · 发表于：PLoS Medicine · 年份：2024 · DOI：10.1371/journal.pmed.1004329 · 被引用次数：17 · 研究领域：HIV Research and Treatment、HIV/AIDS drug development and treatment、Biological Research and Disease Studies

BACKGROUND: Broadly neutralizing antibodies (bnAbs) are a promising approach for HIV-1 prevention. In the Antibody Mediated Prevention (AMP) trials, a CD4-binding site targeting bnAb, VRC01, administered intravenously (IV), demonstrated 75% prevention efficacy against highly neutralization-sensitive viruses but was ineffective against less sensitive viruses. VRC07-523LS is a next-generation bnAb targeting the CD4-binding site and was engineered for increased neutralization breadth and half-life. We conducted a multicenter, randomized, partially blinded Phase I clinical trial to evaluate the safety and serum concentrations of VRC07-523LS, administered in multiple doses and routes to healthy adults without HIV. METHODS AND FINDINGS: Participants were recruited between 2 February 2018 and 9 October 2018. A total of 124 participants were randomized to receive 5 VRC07-523LS administrations via IV (T1: 2.5 mg/kg, T2: 5 mg/kg, T3: 20 mg/kg), subcutaneous (SC) (T4: 2.5 mg/kg, T5: 5 mg/kg), or intramuscular (IM) (T6: 2.5 mg/kg or P6: placebo) routes at 4-month intervals. Participants and site staff were blinded to VRC07-523LS versus placebo for the IM group, while all other doses and routes were open-label. Safety data were collected for 144 weeks following the first administration. VRC07-523LS serum concentrations were measured by ELISA through Day 112 in all participants and by binding antibody multiplex assay (BAMA) thereafter in 60 participants (10 per treatment group) through Day...