Safety and virologic effect of the HIV-1 broadly neutralizing antibodies, VRC01LS or VRC07-523LS, administered to HIV-infected adults in a phase 1 clinical trial
Background: VRC 607/ACTG 5378 is a two-part study conducted by the VRC and ACTG investigating the CD4 binding site HIV-1 broadly neutralizing antibodies (bNAbs) VRC01LS (Part A) and VRC07-523LS (Part B) in treatment naïve HIV-infected adults. The study objectives were to evaluate safety and tolerability (primary) and antiviral activity and pharmacokinetic (PK) parameters (secondary).
Methods: 16 HIV-infected viremic adults between the ages of 18-70 were enrolled. Seven participants in Part A received one intravenous (IV) dose of 40 mg/kg VRC01LS, and nine participants in Part B received one IV dose of 40 mg/kg VRC07-523LS. Safety was evaluated by collection of local and systemic reactogenicity symptoms for three days and adverse events (AEs) for 56 days post product administration. Blood samples were collected at pre-specified study timepoints for viral load and PK analysis as well as CD4/8 T-cell counts and safety labs. The study is ongoing at the time of this report.
Results: In Part A, VRC01LS was safe and well tolerated. No local reactogenicity was reported and systemic reactions (n=1) were mild. There were no AEs related to the study product. Seven days post-infusion, 3/7 participants had at least a 0.5 log10 decrease in viral load (Fig. 1A). In Part B, VRC07-523LS was safe and well tolerated. Local (n=3) and systemic (n=2) reactogenicity were mild. Two AEs were assessed as related to the study product; infusion site paraesthesia and decreased neutrophil count, both which resolved with no residual effects the day of infusion and 8 days following onset, respectively. Seven days post-infusion, 8/9 participants had at least 1.2 log10 decrease in viral load (Fig. 1B).
Conclusions: Both VRC01LS and VRC07-523LS were safe and well-tolerated when administered to viremic HIV-infected adults. Antiviral activity > 0.5 log was observed in 3/7 VRC01LS recipients and >1.2 log for 8/9 VRC07-523LS recipients.
[Post antibody administration viral load]
G. Chen1, E. Coates1, C. Fichtenbaum2, S. Koletar3, R. Landovitz4, R. Presti5, T. Overton6, J. Santana7, R.S. Rothwel1, J. Roa8, E. Donaghy9, L. Holman1, L. Novik1, N. Berkowitz1, B. Larkin1, M. Conan-Cibotti1, R. Tressler10, J. Wang11, Z. Hu11, E. Capparelli12, F. Arnold1, R. Bailer1, A. McDermott1, L. Gama1, B. Graham1, R. Koup1, J. Mascola1, J. Ledgerwood1, P. Tebas9, VRC 607/ACTG A5378 study team
1Vaccine Research Center, NIAID, NIH, Bethesda, United States, 2University of Cincinnati, Cincinnati, United States, 3Ohio State University CRS, Division of Infectious Diseases, Columbus, United States, 4University of California, Los Angeles, Center for Clinical AIDS Research & Education Center CRS, Los Angeles, United States, 5Washington University School of Medicine, Division of Infectious Disease, St. Louis, United States, 6Alabama CRS, Alabama Vaccine Research Clinic at UAB, Birmingham, United States, 7University of Puerto Rico School of Medicine, Proyecto ACTU-Infectious Disease Section, San Juan, United States, 8Social and Scientific Systems, Silver Spring, United States, 9Hospital of University of Pennsylvania, Clinical Research Site, Philadelphia, United States, 10National Institute of Allergy and Infectious Diseases, National Institutes of Health, HIV Research Branch, Therapeutic Research Program, Division of AIDS, Rockville, United States, 11National Institute of Allergy and Infectious Diseases, National Institutes of Health, Biostatistics Research Branch, Division of Clinical Research, Bethesda, United States, 12University of California San Diego, School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences, San Diego, United States