Safety, Tolerability and Immunogenicity of MVA.HTI and ChAdOx1.HTI With Vesatolimod in HIV-1 Positive Patients
Condition: HIV/AIDS
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections
Study type: Interventional
Phase: Phase 2

Summary: 
      AELIX-003 study aims to investigate the safety, tolerability, immunogenicity and efficacy of
      a regimen containing AELIX Therapeutics' HTI T-cell vaccines and Gilead´s Toll-Like Receptor
      7 (TLR7) agonist vesatolimod in HIV-infected individuals on antiretroviral therapy. Study
      that will be conducted in 57 participants who have started antiretroviral therapy during
      early HIV infection, enrolled at various clinical trial sites in Spain. All participants will
      be on antiretroviral therapy upon starting the study, with their HIV viral loads <50
      copies/mL. Following exposure to the vaccine/vesatolimod, all participants, under careful
      monitoring, will temporarily stop their antiretroviral drugs to determine if the intervention
      is effective in keeping their HIV levels under control.
    

Detailed description: 
      Study will evaluate safety of the investigational drugs ChAdOx1.HTI and MVA.HTI (referenced
      collectively as CCMM) with vesatolimod (also known as GS-9620) in participants with early
      treated HIV-1 infection.

      The current study will also investigate the immunogenicity of CCMM + vesatolimod treatment
      and the impact of CCMM + vesatolimod treatment on viral rebound and viral control following
      an analytical treatment interruption (ATI) in participants with early treated HIV-1
      infection.

      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 that includes 2 vaccine components. 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. In this double blind, randomised, safety and tolerability study (AELIX-003),
      the HTI immunogen will be administered in a prime-boost regimen consisting of vaccinations
      with ChAdOx1.HTI (prime) and MVA.HTI (boost).

      The treatment regimen in this study will also include a toll-like receptor 7 (TLR7) agonist,
      GS-9620, which is supported by a recent non clinical study where sequential administration of
      vaccines and a TLR7 agonist (GS-986, an analogue of vesatolimod) demonstrated efficacy in
      simian immunodeficiency virus (SIV)-infected rhesus monkeys on ART.

      HTI is currently being tested in the Phase I, double blind, placebo controlled clinical study
      AELIX-002 through a heterologous prime-boost vaccination employing 3 products expressing the
      HTI antigen, DNA.HTI and MVA.HTI and ChAdOx.HTI. The available clinical data from AELIX-002
      do not suggest a risk for serious adverse events (SAEs) from the products alone, used
      sequentially, or from the immunogen itself.

      The study will screen HIV-1 infected participants who have initiated ART within 180 days (6
      months) of the estimated date of HIV-1 acquisition and who have achieved virological
      suppression for at least 1 year prior entering AELIX-003. Participants who provide informed
      consent and meet study entry criteria will be randomised into 1 of 2 parallel treatment
      groups. The study will be conducted in 3 periods: Period 1 will last 48 weeks during which
      participants will receive blinded IMPs and will continue their ART regimen; Period 2 will
      last up to 24 weeks during which participants will discontinue their ART regimen; and Period
      3 will last 12 weeks during which participants will be monitored following the restart of
      their ART.
    

Intervention name(s): ChAdOx1.HTI; MVA.HTI; GS-9620; Placebo; Placebo Oral Tablet
Intervention type(s): Biological; Biological; Drug; Biological; Drug
Intervention description(s): ChAdOx1.HTI at week 0 and week 12; Vaccine delivered as one 0. 5 mL IM injection; MVA.HTI at week 24 and week 36; Vaccine delivered as one 0. 5 mL IM injection; GS-9620 at week 26,28,30,32,34,38,40,42,44 and 46 Unit-dose tablet, delivered as two 3-mg tablets; Saline placebo delivered as one 0. 5 mL IM injection; Unit-dose placebo tablet delivered as two 3-mg placebo tablets
Other intervention name(s): Vesatolimod; N/H
Intervention MeSH terms: Vesatolimod
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: double-blind, placebo-controlled
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: HIV infection; Therapeutic Vaccines; HTI; TLR7