The Safety and Immunogenicity of the DNA-GTU Vaccine Administered to HIV-infected Patients on ART vs Placebo
Condition: HIV
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      CUT*HIVTHER 001 is a randomised placebo-controlled Phase I/II study aimed at exploring the
      safety and immunogenicity of two different modes of delivery of a GTU® DNA plasmid vaccine
      (GTU®-multiHIV B clade) in HIV infected volunteers on antiretroviral therapy (ART):

        -  Transcutaneous (TC) delivery to enhance intramuscular delivery and

        -  Electroporation (EP) enhanced intramuscular delivery Participants will be randomised
           1:1:1 to TC:EP:saline for the purposes of analysis. Half the saline group will receive
           TC saline and half will receive EP saline.

           30 HIV infected male and female volunteers aged 18-45 years, who have been on ART for at
           least 6 months with 2 or more HIV plasma viral load measurements < 50 copies HIV RNA/ml
           prior to enrolment.

      The investigational HIV-1 vaccine GTU®-MultiHIV B clade encodes for a MultiHIV antigen which
      is a synthetic fusion protein consisting of full-length polypeptides of Rev, Nef, Tat, p17
      and p24 and containing more than 20 Th and CTL epitopes of protease, reverse transcriptase
      (RT) and gp160 regions of the HAN2 HIV-1 B clade.

      Vaccine is provided in sealed vials at 2mg/ml, and a single 1ml IM injection of 2mg
      GTU®-MultiHIV DNA IM (into the thigh) is required to deliver a 2mg dose. Individuals in Group
      2 will receive a further 0.4mg GTU®-MultiHIV DNA in 0.2ml administered by TC, a novel
      needle-free method of vaccine delivery.
    

Detailed description: 
      The investigators are exploring combination regimens with the overall aims of (i) optimising
      immune responses and (ii) developing safe and well tolerated strategies which will favour the
      development of T-cell responses that may enhance anti-HIV HIV therapy with the forward
      looking goal of working towards functional eradication of infection. The investigator
      proposes to combine the previously used IM and TC methods because preclinical data suggest
      that the combination of methods will favour the development of CD8 T cell responses. All
      groups will receive 6.0mg of the vaccine IM given in 3 doses over 12 weeks. Group 1 will
      receive the 6.0mg IM with electroporation (EP) and Group 2 will receive the 6.0mg IM without
      EP but together with an additional 1.2mg vaccine TC. The primary immunogenicity endpoint will
      be to determine whether either intervention group augments the cellular responses to vaccine
      specific peptides in relation to baseline. It is anticipated that none of subjects receiving
      saline placebo would have an increase in vaccine specific responses relative to those at
      baseline. Therefore if the differences between the active groups and saline placebo are
      sufficiently large, for example 80% responders in a GTU®-MultiHIV DNA active group, <10% in
      the control group, this would be significant.

      Should the regimes prove safe, acceptable and induce significant immunogenicity then the
      intention is to move one or both regimes into a larger study powered to determine their
      potential long-term impact on therapy when used in combination with conventional ARV
      regimens. Proof of concept that DNA vaccination can induce de novo HIV specific responses
      that are associated with control of viral replication, would justify further investigation of
      their use in immunotherapies combined with ART intensification and/or anti-latency drugs.
    

Intervention name(s): GTU®-MultiHIV B Clade Vaccine; Sodium chloride BP
Intervention type(s): Biological; Other
Intervention description(s): The investigational HIV-1 vaccine GTU®-MultiHIV B clade encodes for a MultiHIV antigen (synthetic fusion protein) built up by full-length polypeptides of Rev, Nef, Tat, p17 and p24 with more than 20 Th and CTL epitopes of protease, reverse transcriptase (RT) and gp160 regions of an HAN2 HIV-1 B clade isolate.; For use in prophylactic and replacement therapy, requiring the use of isotonic saline solution.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Human Immunodeficiency Virus; Immunodeficiency Virus, Human