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
Condition: HIV-1 Infection
MeSH terms: Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a double blind, randomized, placebo-controlled, parallel design, study in which 24
      HIV-infected participants with durable viral suppression will be randomly assigned to receive
      vaccination with MVA.tHIVconsv3 (M3), MVA.tHIVconsv4 (M4), M3+M4 combined, or placebo.
      Participants will be randomized 7:7:7:3 to one of four study arms, and receive study
      treatment or placebo at Day 0. Each enrolled participant will complete the study in
      approximately 33.5 weeks (8.4 months).

      The purpose of this study is to find out:

        -  If it is safe for people to receive injections of two investigational HIV vaccines,
           called MVAtHIVconsv3 and MVAtHIVconsv4 alone or in combination.

        -  If giving participants these vaccine doses will increase their immune system's ability
           to kill HIV virus.
    

Detailed 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 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.
    

Intervention name(s): MVA.tHIVconsv3; MVA.tHIVconsv4; Placebo
Intervention type(s): Biological; Biological; Other
Intervention description(s): viral-vector, MVA, expressing immunogens derived from conserved yet immunogenic regions of HIV-1; viral-vector, MVA, expressing immunogens derived from conserved yet immunogenic regions of HIV-1; The appropriate amount of Sodium Chloride for Injection USP, 0.9% will be drawn into a syringe.
Other intervention name(s): M3; M4; Normal saline, Sodium Chloride
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants will be randomized 7(M3):7(M4):7(M3+M4):3(Placebo) to one of four study arms, and receive study treatment or placebo at Day 0.
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: HIV-1; Infection; Suppressed; ART; Vaccines; Alone; Combination; Immunogenicity