HIV Monoclonal Antibody Studies

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

Abstract

This Vaccine Research Center (VRC) Clinical Trials Program (CTP) project is for clinical trials related to passive immunity (monoclonal antibodies) directed against HIV, evaluated in healthy volunteers and HIV-infected volunteers. A brief summary of each study to date follows. VRC 601 (13-I-0189) is the first Phase I dose-escalation study in HIV-infected volunteers of a human monoclonal antibody, identified as VRC-HIVMAB060-00-VP (VRC01), which has broad HIV-1 neutralizing activity and was developed by the VRC/NIAID/NIH. Sci Transl Med. 2015 Dec 23;7(319):319ra206. VRC 602 (14-I-0019) was a Phase 1 dose-escalation study of the safety and pharmacokinetics of human monoclonal antibody VRC01, administered intravenously or subcutaneously to healthy adults. The study initiated in FY14. Clin Exp Immunol. 2015 Dec;182(3):289-301. VRC 606 (16-I-0018) wds the first study of a new generation of highly potent and broadly neutralizing HIV-1 human MAb, VRC01LS, targeted against the HIV-1 CD4 binding site. The study examined safety, tolerability and pharmacokinetics. VRC01LS was being administered to healthy adults by the intravenous and subcutaneous routes. The study was initiated in FY16 and accrual completed in FY17. PLoS Med. 2018 Jan 24;15. VRC 607 (16-I-0147) is the first Phase I single dose study of the safety and virologic effect of monoclonal antibody VRC01LS administered intravenously to HIV-infected adults. VRC01LS is a next generation MAb developed by the VRC to extend the antibody half-life. This study began enrolling in FY16 and the last subject last visit occurred in FY19. Functional neutralization assay testing is ongoing. VRC 605 (17-I-0030) was a Phase 1 dose-escalation study of the safety and pharmacokinetics of human monoclonal antibody VRC07-523LS administered intravenously or subcutaneously to healthy adults. The study was initiated and accrual completed in FY17. Lancet HIV. 2019 Oct;6(10):e667-e679. VRC 603 (18-I-0030) is the first phase I dose-escalation study of the safety of AAV8-VRC07 (VRC-HIVAAV070-00-GT) recombinant AAV vector expressing VRC07 HIV-1 neutralizing antibody in antiretroviral treated, HIV-1 infected adults with controlled viremia. This trial opened in FY18 and enrollment was completed in FY21. Follow-up continues through FY25. A paper describing the safety and tolerability of the study product, serum levels of VRC07, anti-drug antibody levels, and neutralizing activity of VRC07 was published. Nat Med. 2022 May;28(5):1022-1030. doi: 10.1038/s41591-022-01762-x. Epub 2022 Apr 11. PMID: 35411076. A future follow-up publication is planned. VRC 609 (18-I-0105) is a phase I dose-escalation study of the safety and pharmacokinetics of human monoclonal antibody, N6LS, administered intravenously or subcutaneously to healthy adults. The study was initiated in FY18 and last enrollment occurred in FY22. Last study visit will occur in FY22. Data analysis will proceed after this point. VRC 610 (18-I-0113) is a phase I safety and pharmacokinetics study to evaluate human monoclonal antibody 10E8VLS administered alone or concurrently with monoclonal antibody VRC07-523LS via subcutaneous injection in healthy adults. The study was initiated in FY18. Eight subjects were infused subcutaneously with study product. Six subjects received 10E8VLS and 2 subjects received 10E8VLS plus VRC07-523LS. No subjects were re-dosed. Due to prolonged local reactogenicity and a poor pharmacokinetic profile, the trial was voluntarily terminated by the Sponsor and Principal Investigator. VRC 611 (20-I-0096) is a phase 1 study evaluating the safety and Pharmacokinetics of human monoclonal antibody CAP256V2LS administered intravenously or subcutaneously as one dose at 5 mg/kg. The study opened to enrollment in FY22, enrolling 10 participants. The last follow-up visit will occur in FY22. The last study visit will occur in FY23 after which data analysis will commence.