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HIVPhase 1NCT03204617

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

A Phase 1 study testing DNA.HTI 0.5mL at weeks 0, 4 and 8 + MVA.HTI 0.5mL at weeks 12 and 20 (DDDMM) and At least 24 weeks since DDDMM, ChAdOx1.HTI 0.5mL at weeks 0 and 12 + MVA.HTI 0.5mL at week 24 (CCM) in people with HIV, run by Aelix Therapeutics at 1 site in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 60 years
Conditions the study is for
HIV
What is being tested?
DNA.HTI 0.5mL at weeks 0, 4 and 8 + MVA.HTI 0.5mL at weeks 12 and 20 (DDDMM) and At least 24 weeks since DDDMM, ChAdOx1.HTI 0.5mL at weeks 0 and 12 + MVA.HTI 0.5mL at week 24 (CCM)
Type of treatment
Vaccines
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
45 participants
Where
1 siteSpain
Study dates
7 Jul 2017to 10 Mar 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Confirmed HIV-1 infection
  • On combined antiretroviral treatment (defined as ≥ 3 antiretroviral drugs) initiated within 6 months of estimated time of HIV-1 acquisition.
  • Willing and able to be adherent to their cART regimen for the duration of the study.
  • Optimal virological suppression for at least 1 year defined as maintained pVL below the limit of detection (based on current available assays, 20, 40 or 50 copies/ml) allowing for isolated blips.
  • Being on the same cART regimen for at least 4 weeks at screening visit.
  • Nadir CD4 count ≥ 200 cells per mm3. Isolated lower counts at the moment of acute HIV-1 infection will be allowed only if appropriate immune recovery was followed after cART initiation (as is criteria 7).
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  • Stable CD4 counts ≥ 400 cells per mm^3 for the last 6 months at screening visit.
  • Availability of stored biological sample (including PBMC and plasma) before any cART initiation.
  • Aged at least 18 years on the day of screening and no greater than 60 years on the day of the first vaccination.
  • Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study.
  • In the opinion of the principal investigator or designee, the patient has understood the information provided and capable of giving written informed consent.
  • If heterosexually active female; using an effective method of contraception (hormonal contraception, intra-uterine device (IUD), or anatomical sterility in self or partner) from 14 days prior to the first vaccination until at least 12 weeks after the last vaccination; all female volunteers must be willing to undergo urine pregnancy tests at time points specified in the Schedule of Procedures.
  • If heterosexually active male; willing to use an effective method of contraception (anatomical sterility in self) or agree on the use of an effective method of contraception by his partner (hormonal contraception, intra-uterine device (IUD), or anatomical sterility) from the day of the first vaccination until 12 weeks after the last vaccination.
  • Willing to accept blood draws and collect stool at time points specified in the Schedule of Procedures.
  • Willing to forgo donating blood during the study.

Who cannot join

  • Pregnancy or lactating.
  • Presence of resistance drug mutations in a pre-cART genotype.
  • Reported periods of suboptimal adherence to cART.
  • History of past antiretroviral treatment interruptions longer than 2 weeks.
  • Participation in another clinical trial within 12 weeks of study entry (at screening visit).
  • Any AIDS-defining disease or progression of HIV-related disease.
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  • History of autoimmune disease.
  • History or clinical manifestations of any physical or psychiatric disorder which could impair the subject's ability to complete the study.
  • Receipt of approved vaccines within 2 weeks of study entry and along the duration of the trial.
  • History of anaphylaxis or severe adverse reaction to vaccines.
  • Previous immunisation with any experimental immunogens.
  • Receipt of blood products within 6 months of study entry.
  • Treatment for cancer or lymphoproliferative disease within 1 year of study entry.
  • Any other current or prior therapy which, in the opinion of the investigators, would make the individual unsuitable for the study or influence the results of the study.
  • Current or recent use (within last 3 months) of interferon or systemic corticosteroids or other immunosuppressive agents (use on inhaled steroids for asthma or topic steroids for localized skin conditions are permitted).
  • Any laboratory abnormalities including:
  • Haematology
  • Haemoglobin < 10.0 g/dl
  • Absolute Neutrophil Count (ANC) ≤ 1,000 /mm3
  • Absolute Lymphocyte Count (ALC) ≤ 600 /mm3
  • Platelets ≤100,000 /mm3, ≥ 550,000 /mm3
  • Biochemistry
  • Creatinine > 1.3 x ULN
  • Aspartate aminotransferase (AST) > 2.5 x ULN
  • Alanine aminotransferase (ALT) > 2.5 x ULN
  • Microbiology
  • Positive for hepatitis B surface antigen,
  • Positive for hepatitis C antibody, unless confirmed clearance of HCV infection (spontaneous or following treatment)
  • Positive serology indicating active syphilis requiring treatment
  • Complete refusal to cART interruption

Trial locations and contacts

1 site in 1 country.

Spain1 site
  • IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol

    Badalona, Barcelona, 08916

Other trials in Spain

About this study

Official title: A Phase I, Randomized, Double-Blind, Placebo-Controlled Safety, Tolerability and Immunogenicity Study of Candidate HIV-1 Vaccines DNA.HTI, MVA.HTI and ChAdOx1.HTI in Early Treated HIV-1 Positive Individuals

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.

Read the 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.

Conditions
HIV
Being tested
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
Keywords
HIV infection, First in Human, Therapeutic Vaccines, HTI, HIV reservoir
Medical subject headings
HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DNA.HTI 0.5mL at weeks 0, 4 and 8 + MVA.HTI 0.5mL at weeks 12 and 20 (DDDMM)Biological

    Also called N/H

    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 DDDMM, ChAdOx1.HTI 0.5mL at weeks 0 and 12 + MVA.HTI 0.5mL at week 24 (CCM)Biological

    Also called N/H

    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.

  • PlaceboDrug

    Also called N/H

    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

Study groups in NCT03204617
Study groupRoleWhat they receive
DDDMM + CCMExperimentalDNA.HTI 0.5mL at weeks 0, 4 and 8 + MVA.HTI 0.5mL at weeks 12 and 20. 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.
Receives: Biological: DNA.HTI 0.5mL at weeks 0, 4 and 8 + MVA.HTI 0.5mL at weeks 12 and 20 (DDDMM); Biological: At least 24 weeks since DDDMM, ChAdOx1.HTI 0.5mL at weeks 0 and 12 + MVA.HTI 0.5mL at week 24 (CCM)
PlaceboPlacebo comparator0.9% sterile normal saline solution at weeks 0, 4, 8, 12 and 20. At least 24 weeks since fifth placebo administration, administration of 0.9% sterile normal saline solution at weeks 0, 12 and 24.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: From first DNA.HTI/Placebo administration to week 32 and from first ChAdOx1.HTI/Placebo administration to week 32

  2. 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

    Measured: From first DNA.HTI/Placebo administration to week 32 and from first ChAdOx1.HTI/Placebo administration to week 32

Secondary outcomes (12)
  1. 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

    Measured: From first DNA.HTI/Placebo administration to week 32 and from first ChAdOx1.HTI/Placebo administration to week 32

  2. 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

    Measured: From first DNA.HTI/Placebo administration to week 32 and from first ChAdOx1.HTI/Placebo administration to week 32

  3. 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

    Measured: From first DNA.HTI/Placebo administration to week 32 and from first ChAdOx1.HTI/Placebo administration to week 32

  4. 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

    Measured: From ATI start (visit Phase C week 32) to weeks 12 and 24 after ATI start (visits Phase C week 44 and week 56).

  5. 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

    Measured: From ATI start (visit Phase C week 32) to weeks 12 and 24 after ATI start (visits Phase C week 44 and week 56).

  6. 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).

    Measured: From ATI start (visit Phase C week 32) to first occurrence of detectable pVL (>50 copies/mL) up to week 56

  7. 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.

    Measured: From ATI start (visit Phase C week 32) to first occurrence of pVL >10,000 copies/mL up to week 56

  8. 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).

    Measured: From ATI start (visit Phase C week 32) to weeks 12 and 24 after ATI start (visits Phase C week 44 and week 56).

  9. 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).

    Measured: From ATI start (visit Phase C week 32) to cART resumption through study completion, up to week 68

  10. 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.

    Measured: From ATI start (visit Phase C week 32) to cART resumption up to week 56

  11. 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).

    Measured: From ATI start (visit Phase C week 32) to cART resumption up to week 56

  12. 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.

    Measured: 12 weeks after cART resumption.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jul 2017
  2. Study start7 Jul 2017
  3. Primary completion1 Jul 2020
  4. Study completion10 Mar 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03204617
Sponsor's protocol ID
AELIX-002
Status last verified
Apr 2021
First submitted
13 Jun 2017
Last updated
8 Apr 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Bailon L, Llano A, Cedeno S, Escriba T, Rosas-Umbert M, Parera M, Casadella M, Lopez M, Perez F, Oriol-Tordera B, Ruiz-Riol M, Coll J, Perez F, Rivero A, Leselbaum AR, McGowan I, Sengupta D, Wee EG, Hanke T, Paredes R, Alarcon-Soto Y, Clotet B, Noguera-Julian M, Brander C, Molto J, Mothe B; AELIX002 Study Group. Safety, immunogenicity and effect on viral rebound of HTI vaccines in early treated HIV-1 infection: a randomized, placebo-controlled phase 1 trial. Nat Med. 2022 Dec;28(12):2611-2621. doi: 10.1038/s41591-022-02060-2. Epub 2022 Oct 27.

    PubMed 36302893

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing DNA.HTI 0.5mL at weeks 0, 4 and 8 + MVA.HTI 0.5mL at weeks 12 and 20 (DDDMM) and At least 24 weeks since DDDMM, ChAdOx1.HTI 0.5mL at weeks 0 and 12 + MVA.HTI 0.5mL at week 24 (CCM) in people with HIV, run by Aelix Therapeutics at 1 site in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of participants that develop Grade 3 or 4 local reactions (time frame: From first DNA.HTI/Placebo administration to week 32 and from first ChAdOx1.HTI/Placebo administration to week 32). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03204617, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2021.

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