HIV-1 Infected Adults With Controlled Viremia Clinical Trial
Official title:
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
Background: The Human Immunodeficiency Virus (HIV) attacks the immune system. Scientists have created a gene that could be transferred to the cells of people with HIV. The gene should tell the cells to make an antibody called VRC07. This antibody fights HIV. The VRC07 gene is packaged into a man-made version of a virus called AAV8. Objectives: To see if AAV8-VRC07 is safe. To study if it causes cells to produce the VRC07 antibody. Eligibility: Adults ages 18-65 who are HIV infected but in general good health and have been taking the same HIV medicine for at least 3 months Design: Participants were screened in a different protocol. Participants received the study product on day 1. It was injected one or more times in the upper arm or thigh using a needle. Participants weight was measured to calculate the dose. Women may have had a pregnancy test. For 7 days after getting the study product, participants checked their temperature with a thermometer. They noted any symptoms in an electronic or paper diary. Participants will have study visits. At each one, they will have a physical exam and medical history. They will have blood drawn and may have saliva collected. The study visit schedule is as follows: For 12 weeks: 1 visit a week For the next 12 weeks: 1 visit every other week Then about 1 visit a month After 1 year in the study: a visit every 6 months for the next 4 years. Total study participation is 5 years.
Design: This is a Phase I study of the safety and tolerability of AAV8-VRC07 (VRC-HIVAAV070-00-GT) expressing VRC07 human monoclonal antibody with broad HIV-1 neutralizing activity in HIV-1 infected adults. It is a dose-escalation study to examine pharmacokinetics of VRC07 expression following intramuscular (IM) administration of AAV8-VRC07 in participants on anti-retroviral therapy (ARV). The hypotheses are: 1) AAV8-VRC07 will be safe for human administration and will not elicit hypersensitivity or anti-drug antibody (ADA) to VRC07; and 2) intramuscular delivery of AAV8-VRC07 will result in production of biologically active VRC07 antibody at a concentration in serum that is measurable and safe. Description: AAV8-VRC07 was developed by VRC, NIAID, NIH, and manufactured by the Clinical Vector Core, Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia (CHOP), Philadelphia, Pennsylvania (PA). It is composed of an AAV8 recombinant vector expressing genes encoding the heavy and light chains of the VRC07 monoclonal antibody. AAV8-VRC07 was supplied at 2.84 x 10^13 vector genomes (vg)/mL. Participants: HIV-1 infected adult volunteers (18 to 65 years old) on a stable antiretroviral regimen for more than or equal to 3 months, with controlled viremia, under the care of a physician, and without additional clinically significant medical conditions. Study Plan: There are 3 dose escalation groups. Sequentially enrolled participants were assigned to the dosage level being evaluated at the time of enrollment. All injections were administered intramuscularly (IM) by needle and syringe. Cumulative safety data were reviewed weekly by a Protocol Safety Review Team (PSRT) that included an Independent Safety Monitor (ISM) while injections were being administered. Safety, including reactogenicity and unsolicited adverse events (AEs), laboratory findings, pharmacokinetics, and VRC07 antibody levels in blood were assessed after the injection and summarized for an interim analysis at 4 weeks post injection. The second participant in each dose group was injected after the 4 weeks safety assessment for the first participant. Decisions regarding dose escalation and participant enrollments were based on safety data and the VRC07 concentration in blood at 4 weeks after product administration. The pharmacokinetics of VRC07 at each dose level was evaluated to determine the dose that would result in antibody production that achieves at least 50 mcg/mL VRC07 concentration in serum at 4 weeks post injection with a target set point of more than or equal to 5 mcg/mL at 12 weeks post injection. ;