Safety and Immunogenicity Study of DNA.HTI, MVA.HTI and ChAdOx1.HTI in HIV-1-positive Patients (AELIX-002)
Condition: HIV
Study type: Interventional
Phase: Phase 1

Summary: 
      The AELIX-002 study aims to evaluate the safety and the immunogenicity of an heterologous
      prime-boost regimen with DNA.HTI, MVA.HTI and ChAdOx1.HTI in early diagnosed and treated
      HIV-1 positive individuals, males and females,18-60 years of age.
    

Detailed description: 
      AELIX Therapeutics has developed a novel immunogen, which was designed to be used as a a
      therapeutic HIV vaccine that could help HIV infected individuals to control viral replication
      in the absence of antiretroviral treatment. HIVACAT T cell immunogen (HTI) is a novel T cell
      immunogen covering the most vulnerable regions of HIV. The encoding DNA sequence that has
      been inserted in various vaccine vectors, including viral and non-viral vectors.
      Administration of the HTI immunogen is implemented through a heterologous prime-boost
      approach. The aim of the sequential administration of the therapeutic vaccines is to achieve
      a so-called "functional cure," in which HIV-infected participants can control viral
      replication in the absence of ART.

      The AELIX-002 Phase I study will evaluate the safety and immunogenicity of an heterologous
      regime with DNA.HTI, MVA.HTI and ChAdOx1.HTI in HIV-1 positive participants on suppressive
      antiretroviral treatment who started Combination Antiretroviral Therapy (cART) within the
      first 6 months of confirmed HIV-1 acquisition. In Phase A, participants were randomized to
      receive active vaccine or placebo in a double blinded fashion. There was a sentinel group of
      three participants; two received active vaccine and one received placebo (0.9% normal
      saline). During the sentinel phase of the study only one participant was enrolled per day.
      Two weeks later and in the absence of any related SAE or ≥ Grade 3 adverse event lasting >72h
      after vaccination in any of the 3 sentinel participants, six individuals in the remaining
      cohort were enrolled (in blocks of 3 patients per day) and the final six participants one
      week later, also in blocks of 3 participants per day. On each vaccination day, 2 participants
      received active IMP and 1 received placebo (2:1).

      After the first 15 participants (3 sentinel and 12 non-sentinel) have reached week 22 visit
      and a favourable report from the Safety Monitoring Committee has been released, transition to
      Phase B was performed to include 30 participants (Group 3). Participants were recruited
      sequentially and without following blocks of pre-defined number of vaccines and placebos per
      immunization day.

      At week 32, all participants were invited to participate in an extension sub-study (Roll-over
      Phase) to assess long-term safety, tolerability and immunogenicity of DNA.HTI and MVA.HTI
      administrations until start of Phase C. There were no interventions during this extension
      Roll over Phase.

      After a favourable SMC report, transition to Phase C occurred. During Roll-over Phase
      participants in Phase A/B were offered to participate in Phase C. Participants who received
      active treatment (DDDMM) in Phase A/B will continue to receive active treatment (CCM) in
      Phase C, while participants who received placebo in Phase A/B will continue to receive
      placebo (PPP). Treatment allocation remained blind. Eight weeks after the third
      MVA.HTI/placebo administration, all participants will undergo an Analytical Treatment
      Interruption (ATI) of up to 24 weeks of duration. At visit Phase C week 56 (end-of-ATI
      visit), or before according to pre-specified criteria, cART will be resumed, and participants
      will be followed during a safety period of 12 weeks.
    

Intervention name(s): DNA.HTI 0.5mL at weeks 0, 4 and 8 + MVA.HTI 0.5mL at weeks 12 and 20 (DDDMM); At least 24 weeks since DDDMM, ChAdOx1.HTI 0.5mL at weeks 0 and 12 + MVA.HTI 0.5mL at week 24 (CCM); Placebo
Intervention type(s): Biological; Biological; Drug
Intervention description(s): Vaccine DNA.HTI 0.5mL at weeks 0, 4 and 8 + Vaccine MVA.HTI 0.5mL at weeks 12 and 20 (DDDMM).; At least 24 weeks since second MVA.HTI administration (week 20), administration of ChAdOx1.HTI 0.5mL at weeks 0 and 12 + MVA.HTI 0.5mL at week 24.; 0.9% sterile normal saline solution at weeks 0, 4, 8, 12 and 20. At least 24 weeks since the fifth Placebo administration, 0.9% sterile normal saline solution at weeks 0, 12 and 24
Other intervention name(s): N/H; N/H; N/H
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: HIV infection; First in Human; Therapeutic Vaccines; HTI; HIV reservoir