Evaluating the Safety and Efficacy of the VRC01 Antibody in Reducing Acquisition of HIV-1 Infection Among Men and Transgender Persons Who Have Sex With Men

Summary

This study will evaluate the safety and efficacy of the human monoclonal antibody (mAb) VRC-HIVMAB060-00-AB (VRC01) in preventing HIV-1 infection among men and transgender (TG) persons who have sex with men, in North America, South America, and Switzerland.

Timeline

Start

2016-04-06

Primary completion

2020-12-01

Completion

2020-12-01

Outcome

Missed primary endpoint

registry Placebo vs Pooled VRC01; p = 0.15; Prevention Efficacy (PE) 26.6 (95% CI -11.7 to 51.8) NCT02716675 ↗

paper VRC01 did not prevent overall HIV-1 acquisition more effectively than placebo PMID 33730454 ↗

Publications

• Results Edupuganti S, Mgodi N, Karuna ST, Andrew P, Rudnicki E, Kochar N, deCamp A, De La Grecca R, Anderson M, Karg C, Tindale I, Greene E, Broder GB, Lucas J, Hural J, Gallardo-Cartagena JA, Gonzales P, Frank I, Sobieszczyk M, Gomez Lorenzo MM, Burns D, Anderson PL, Miner MD, Ledgerwood J, Mascola JR, Gilbert PB, Cohen MS, Corey L; HVTN 704/HPTN 085 study group. Feasibility and Successful Enrollment in a Proof-of-Concept HIV Prevention Trial of VRC01, a Broadly Neutralizing HIV-1 Monoclonal Antibody. J Acquir Immune Defic Syndr. 2021 May 1;87(1):671-679. doi: 10.1097/QAI.0000000000002639.
• Results Mgodi NM, Takuva S, Edupuganti S, Karuna S, Andrew P, Lazarus E, Garnett P, Shava E, Mukwekwerere PG, Kochar N, Marshall K, Rudnicki E, Juraska M, Anderson M, Karg C, Tindale I, Greene E, Luthuli N, Baepanye K, Hural J, Gomez Lorenzo MM, Burns D, Miner MD, Ledgerwood J, Mascola JR, Donnell D, Cohen MS, Corey L; HVTN 703/HPTN 081 Team. A Phase 2b Study to Evaluate the Safety and Efficacy of VRC01 Broadly Neutralizing Monoclonal Antibody in Reducing Acquisition of HIV-1 Infection in Women in Sub-Saharan Africa: Baseline Findings. J Acquir Immune Defic Syndr. 2021 May 1;87(1):680-687. doi: 10.1097/QAI.0000000000002649.
• Results Huang Y, Naidoo L, Zhang L, Carpp LN, Rudnicki E, Randhawa A, Gonzales P, McDermott A, Ledgerwood J, Lorenzo MMG, Burns D, DeCamp A, Juraska M, Mascola J, Edupuganti S, Mgodi N, Cohen M, Corey L, Andrew P, Karuna S, Gilbert PB, Mngadi K, Lazarus E. Pharmacokinetics and predicted neutralisation coverage of VRC01 in HIV-uninfected participants of the Antibody Mediated Prevention (AMP) trials. EBioMedicine. 2021 Feb;64:103203. doi: 10.1016/j.ebiom.2020.103203. Epub 2021 Jan 23.
• Results Huang Y, Zhang L, Eaton A, Mkhize NN, Carpp LN, Rudnicki E, DeCamp A, Juraska M, Randhawa A, McDermott A, Ledgerwood J, Andrew P, Karuna S, Edupuganti S, Mgodi N, Cohen M, Corey L, Mascola J, Gilbert PB, Morris L, Montefiori DC. Prediction of serum HIV-1 neutralization titers of VRC01 in HIV-uninfected Antibody Mediated Prevention (AMP) trial participants. Hum Vaccin Immunother. 2022 Dec 31;18(1):1908030. doi: 10.1080/21645515.2021.1908030. Epub 2021 Jul 2.
• Results Corey L, Gilbert PB, Juraska M, Montefiori DC, Morris L, Karuna ST, Edupuganti S, Mgodi NM, deCamp AC, Rudnicki E, Huang Y, Gonzales P, Cabello R, Orrell C, Lama JR, Laher F, Lazarus EM, Sanchez J, Frank I, Hinojosa J, Sobieszczyk ME, Marshall KE, Mukwekwerere PG, Makhema J, Baden LR, Mullins JI, Williamson C, Hural J, McElrath MJ, Bentley C, Takuva S, Gomez Lorenzo MM, Burns DN, Espy N, Randhawa AK, Kochar N, Piwowar-Manning E, Donnell DJ, Sista N, Andrew P, Kublin JG, Gray G, Ledgerwood JE, Mascola JR, Cohen MS; HVTN 704/HPTN 085 and HVTN 703/HPTN 081 Study Teams. Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition. N Engl J Med. 2021 Mar 18;384(11):1003-1014. doi: 10.1056/NEJMoa2031738.
• Weiner JA, Banks LA, Natarajan H, Lin S, Sami S, Kovacikova G, Carpenter MC, Ackerman ME. Drawing a line in the sand: impact of analytical choices on anti-drug antibody cut-points and testing outcomes. Bioanalysis. 2026 Jul 14:1-12. doi: 10.1080/17576180.2026.2698615. Online ahead of print.
• Reeves DB, Mayer BT, deCamp AC, Huang Y, Zhang B, Carpp LN, Magaret CA, Juraska M, Gilbert PB, Montefiori DC, Bar KJ, Cardozo-Ojeda EF, Schiffer JT, Rossenkhan R, Edlefsen P, Morris L, Mkhize NN, Williamson C, Mullins JI, Seaton KE, Tomaras GD, Andrew P, Mgodi N, Ledgerwood JE, Cohen MS, Corey L, Naidoo L, Orrell C, Goepfert PA, Casapia M, Sobieszczyk ME, Karuna ST, Edupuganti S. High monoclonal neutralization titers reduced breakthrough HIV-1 viral loads in the Antibody Mediated Prevention trials. Nat Commun. 2023 Dec 14;14(1):8299. doi: 10.1038/s41467-023-43384-y.
• Huang Y, Zhang L, Karuna S, Andrew P, Juraska M, Weiner JA, Angier H, Morgan E, Azzam Y, Swann E, Edupuganti S, Mgodi NM, Ackerman ME, Donnell D, Gama L, Anderson PL, Koup RA, Hural J, Cohen MS, Corey L, McElrath MJ, Gilbert PB, Lemos MP. Adults on pre-exposure prophylaxis (tenofovir-emtricitabine) have faster clearance of anti-HIV monoclonal antibody VRC01. Nat Commun. 2023 Nov 28;14(1):7813. doi: 10.1038/s41467-023-43399-5.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	VRC01	Monoclonal antibody	10 mg/kg	Intravenous
Subject	VRC01	Monoclonal antibody	30 mg/kg	Intravenous

Indications