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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
QUADRUPLE
Enrollment
45
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
IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, Spain
Proportion of participants that develop Grade 3 or 4 local reactions
Grade 3 or 4 local reactions as assessed by the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events
Time frame: From first DNA.HTI/Placebo administration to week 32 and from first ChAdOx1.HTI/Placebo administration to week 32
Proportion of participants that develop Grade 3 or 4 systemic reactions
Grade 3 or 4 systemic reactions as assessed by the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events
Time frame: From first DNA.HTI/Placebo administration to week 32 and from first ChAdOx1.HTI/Placebo administration to week 32
Proportion of participants that develop T cell responses to HTI-encoded regions
Proportion of patients that develop T cell responses to HTI-encoded regions as determined by IFN-γ ELISPOT assay in vaccine and placebo recipients
Time frame: From first DNA.HTI/Placebo administration to week 32 and from first ChAdOx1.HTI/Placebo administration to week 32
Breadth of total vaccine induced HIV-specific responses
Breadth of total vaccine induced HIV-specific responses measured IFN-γ ELISPOT in vaccine and placebo recipients
Time frame: From first DNA.HTI/Placebo administration to week 32 and from first ChAdOx1.HTI/Placebo administration to week 32
Magnitude of total vaccine induced HIV-specific responses
Magnitude of total vaccine induced HIV-specific responses measured IFN-γ ELISPOT in vaccine and placebo recipients
Time frame: From first DNA.HTI/Placebo administration to week 32 and from first ChAdOx1.HTI/Placebo administration to week 32
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Percentage of participants with viral remission, defined as plasma viral load (pVL) <50 copies/mL 12 and 24 weeks after start of Analytical Treatment Interruption (ATI)
Percentage of participants with viral remission, defined as plasma viral load (pVL) \<50 copies/mL 12 and 24 weeks after start of ATI
Time frame: From ATI start (visit Phase C week 32) to weeks 12 and 24 after ATI start (visits Phase C week 44 and week 56).
Percentage of participants with pVL <2,000 copies/mL at 12 and 24 weeks after start of ATI
Percentage of participants with pVL \<2,000 copies/mL at 12 and 24 weeks after start of ATI
Time frame: From ATI start (visit Phase C week 32) to weeks 12 and 24 after ATI start (visits Phase C week 44 and week 56).
Time to viral detection, defined as the time from ATI start (visit Phase C week 32) to first occurrence of detectable pVL (>50 copies/mL)
Time to viral detection, defined as the time from ATI start (visit Phase C week 32) to first occurrence of detectable pVL (\>50 copies/mL).
Time frame: From ATI start (visit Phase C week 32) to first occurrence of detectable pVL (>50 copies/mL) up to week 56
Time to viral rebound, defined as the time from ATI start (visit Phase C week 32) to first occurrence of pVL >10,000 copies/mL.
Time to viral rebound, defined as the time from ATI start (visit Phase C week 32) to first occurrence of pVL \>10,000 copies/mL.
Time frame: From ATI start (visit Phase C week 32) to first occurrence of pVL >10,000 copies/mL up to week 56
Percentage of participants who remain off cART at 12 and 24 weeks after ATI (visits Phase C week 44 and week 56).
Percentage of participants who remain off cART at 12 and 24 weeks after ATI (visits Phase C week 44 and week 56).
Time frame: From ATI start (visit Phase C week 32) to weeks 12 and 24 after ATI start (visits Phase C week 44 and week 56).
Time off cART, defined as time to cART resumption since ATI start (visit Phase C week 32).
Time off cART, defined as time to cART resumption since ATI start (visit Phase C week 32).
Time frame: From ATI start (visit Phase C week 32) to cART resumption through study completion, up to week 68
Proportion of participants who develop symptoms compatible with acute retroviral syndrome (ARS) during ATI.
Proportion of participants who develop symptoms compatible with acute retroviral syndrome (ARS) during ATI.
Time frame: From ATI start (visit Phase C week 32) to cART resumption up to week 56
Proportion of participants who develop new mutations not present in the pre-cART genotype conferring clinically-significant resistance to antiretroviral drugs (out of the individuals not reaching viral re-suppression 12 weeks after cART resumption).
Proportion of participants who develop new mutations not present in the pre-cART genotype conferring clinically-significant resistance to antiretroviral drugs (out of the individuals not reaching viral re-suppression 12 weeks after cART resumption).
Time frame: From ATI start (visit Phase C week 32) to cART resumption up to week 56
Proportion of participants who suppress pVL to <50 copies/mL 12 weeks after cART resumption.
Proportion of participants who suppress pVL to \<50 copies/mL 12 weeks after cART resumption.
Time frame: 12 weeks after cART resumption.