Study to Assess Safety and Ability to Induce Immune Responses of HIV-1 Vaccines M3 and M4 Given Alone or in Combination in HIV-infected Adults

Summary

Participation Requirements

Description

This is a Phase 1, single site, pilot study to evaluate the safety and immunogenicity of the M3 and M4 vaccines administered alone or in combination in HIV-infected participants suppressed on ART. This is a double blind, randomized, placebo-controlled, parallel design study to evaluate the safety an...

This is a Phase 1, single site, pilot study to evaluate the safety and immunogenicity of the M3 and M4 vaccines administered alone or in combination in HIV-infected participants suppressed on ART. This is a double blind, randomized, placebo-controlled, parallel design study to evaluate the safety and immunogenicity of viral-vector, MVA, expressing immunogens, tHIVconsv3 (M3) and tHIVconsv4 (M4), derived from conserved yet immunogenic regions of HIV-1. The participant population is HIV-1 infected adults suppressed on ART with plasma HIV-1 RNA <50 copies/mL. Hypotheses: The administration of M3 or M4 or M3+M4 together will be safe in HIV-1-infected participants suppressed on ART. The simultaneous administration of M3 with M4 (M3+M4) will result in both an increase in total magnitude of HIV-1-specific T cell responses and increase the breadth of T cells targeting conserved regions of HIV-1 compared with either M3 or M4 vaccination alone. The vaccine and placebo doses will be administered to all participants as an IM (intramuscular) injection in the deltoid muscle of the non-dominant arm, unless a participant requests vaccination in their dominant arm. Participants continue their baseline ART regimen throughout the study. Randomized assignment 7:7:7:3 occurs at Day 0 to one of four arms as provided below: Arm 1 - 7 participants - Treatment: M3 - Dose (pfu): 2x10-8 - Route: IM; Arm 2 - 7 participants - Treatment: M4 - Dose (pfu): 2x10-8 - Route: IM; Arm 3 - 7 participants - Treatment: M3+M4 - Dose (pfu): 1x10-8, each vaccine - Route: IM; Arm 4 - 3 participants - Treatment: Placebo/saline - Dose: N/A - Route: IM; M3 = MVA.tHIVconsv3; M4 = MVA.tHIVconsv4; pfu = plaque forming units; IM = intramuscular The primary safety outcome is the occurrence of at least one ? Grade 3 Adverse Event (AE) including signs/symptoms, lab toxicities, and/or clinical events that are possibly, probably, or definitely related to study treatment through 28 days following vaccination. The primary safety analysis will be blinded through Day 28 after the last dose of vaccine/placebo and the second leukapheresis is completed by the last participant. Screening, Enrollment, and Leukapheresis. The participant reviews and signs the informed consent (ICF). Participants meeting eligibility requirements enroll and undergo one leukapheresis procedure between Day -60 and Day 0. The leukapheresis procedure collects white blood cells allowing for completion of detailed immunologic and virologic assays with minimal blood loss. Participants have the option to consent to a lymph node FNA; participants choosing this option will complete the pre-vaccine FNA between Day -60 and Day 0 and a post-vaccine FNA between Day 7 and Day 21. The post-vaccine FNA should be collected even if the pre-vaccine collection attempt is unsuccessful. Randomization, Study Treatment, Follow-up Assessment, and Leukapheresis. Randomization occurs at Day 0 when a randomization identification number (RID) will be assigned. All participants receive a vaccine or placebo dose as an IM injection. Post vaccination safety assessments occur via clinical evaluations, and lab testing/evaluations. The study will collect research assays at designated visits. At Day 28, all participants will undergo their 2nd leukapheresis. This procedure can be completed between Day 21 through Day 35. The leukapheresis product will be used for immunologic and virologic research assays post vaccine/placebo. Participants will be followed for immunogenicity assessments through Day 70 and safety assessments through Day 168 (Week 24) following the administration of vaccine/placebo at Day 0. Note: The post-vaccine leukapheresis must be done as close to Day 28 as possible. There may be a rare situation where the completion of the procedure in the 2-week visit window will not be possible. As soon as the study coordinator becomes aware of this scenario, the study coordinator should notify the study PI (or designee) to schedule the procedure outside the study window, preferably earlier (between Days 14 and 28). If the procedure can only be done after Day 35, participants should complete the Day 28 visit with collection of a 42.5 mL ACD sample at that visit.

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