AAV8-VRC07 / National Institute of Allergy and Infectious Diseases, National Institutes of Health - LARVOL DELTA

Safety and Tolerability of AAV8 Delivery of a Broadly Neutralizing Antibody in Adults Living With HIV: a Phase 1, Dose-escalation Trial (clinicaltrials.gov) - P1 | N=10 | Active, not recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial primary completion date: Aug 2022 ➔ Aug 2026

Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • CD4

VRC 603: A 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. (clinicaltrials.gov) - P1 | N=10 | Active, not recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial primary completion date: Aug 2026 ➔ Aug 2022

Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • CD4

Systemic Administration and Transient Immunosuppression Eliminate Anti-Drug Antibody Responses Following Vectored Immunoprophylaxis in Mice (ASGCT 2023) - "A more recent Phase I study (VRC603) has demonstrated that administration of AAV8-VRC07 results in long-term systemic expression of VRC07 in humans for up to three years...Finally, we assessed the effect of two immune-suppressing drugs, dexamethasone, and cyclosporine, in inhibiting the ADA response and bNAb expression following VIP and found that dexamethasone, but not cyclosporine, inhibited ADA responses and increased antibody expression in the C57BL/6 mouse model...Importantly, the route of AAV administration had a significant influence on ADA response and bNAb expression. Our results also highlight the feasibility of reducing ADA through transient immunosuppression using dexamethasone."

Preclinical • Human Immunodeficiency Virus • Infectious Disease • CD4

VRC 603: A 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. (clinicaltrials.gov) - P1 | N=10 | Active, not recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Mar 2027 ➔ Aug 2026 | Trial primary completion date: Aug 2022 ➔ Aug 2026

Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • CD4

Safety and tolerability of AAV8 delivery of a broadly neutralizing antibody in adults living with HIV: a phase 1, dose-escalation trial. (PubMed, Nat Med) - P1 | "In this study, we administered a recombinant bicistronic adeno-associated virus (AAV8) vector coding for both the light and heavy chains of the potent broadly neutralizing HIV-1 antibody VRC07 (AAV8-VRC07) to eight adults living with HIV...This ADA response appeared to decrease the production of serum VRC07 in two of these three participants. These data represent a proof of concept that adeno-associated viral vectors can durably produce biologically active, difficult-to-induce bnAbs in vivo, which could add valuable new tools to the fight against infectious diseases."

Journal • P1 data • Human Immunodeficiency Virus • Infectious Disease • CD4

DURABLE HUMAN HIV-SPECIFIC bNAb PRODUCTION 3 YEARS AFTER AAV8-MEDIATED GENE TRANSFER (CROI 2022) - "Vector-based VRC07 production was found in serum from all volunteers given AAV8-VRC07...AAV8 mediated gene transfer may offer a means to generate effective immunoprophylaxis. Identifying the cause of the ADA response may allow further increases in bNAb concentrations."

Gene Therapies • Human Immunodeficiency Virus • Infectious Disease • CD4

VRC 603: A 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. (clinicaltrials.gov) - P1; N=9; Active, not recruiting; Sponsor: National Institute of Allergy and Infectious Diseases (NIAID); Recruiting ➔ Active, not recruiting; N=25 ➔ 9; Trial primary completion date: Mar 2022 ➔ Aug 2022

Clinical • Enrollment change • Enrollment closed • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • CD4

VRC 603: A 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. (clinicaltrials.gov) - P1; N=25; Recruiting; Sponsor: National Institute of Allergy and Infectious Diseases (NIAID); Trial completion date: Mar 2020 ➔ Mar 2027; Trial primary completion date: Jan 2020 ➔ Mar 2022

Clinical • Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • CD4