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Study to Assess the Safety and Durability of Viral Control Beyond 24 Weeks of Analytical Treatment Interruption After the Administration of Candidate HIV-1 Vaccines DNA.HTI, MVA.HTI and ChAdOx1.HTI or Placebo in Early Treated HIV-1 Positive Individuals (ATI Extension of AELIX-002 Study)

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ClinicalTrials.gov Identifier: NCT04385875
Recruitment Status : Recruiting
First Posted : May 13, 2020
Last Update Posted : July 23, 2020
Sponsor:
Collaborator:
Aelix Therapeutics
Information provided by (Responsible Party):
Fundacio Lluita Contra la SIDA

Brief Summary:
The AELIX-002 trial has been conducted on a cohort of individuals who started cART within the first 6 months after the primary VIH infection, thus increasing the likelihood of observing a certain rate of post-treatment controls (PTC), regardless of treatment efficacy. Although the kinetics of HIV rebound should allow observing differences between placebo and control regarding the post treatment controls rate in case of efficacy of the IMPs, assessing the length and determinants of a post-intervention control (PIC) (i.e., associated with vaccination) beyond 24 weeks is crucial for developing a curative approach to HIV infection. In this regard, an extension of the ATI phase for those individuals with pVL less than 2,000 copies/mL after 24 weeks of ATI in the AELIX-002 offers an unique research opportunity to better understand relevant aspects of the mechanisms involved in the different phenotypes of a PIC and PTC.

Condition or disease Intervention/treatment Phase
HIV-1 Infection Biological: Vaccine + extension of the ATI period Other: Placebo + extension of the ATI period Phase 1

Detailed Description:

The AELIX-002 trial has been conducted on a cohort of individuals who started cART within the first 6 months after the primary VIH infection, thus increasing the likelihood of observing a certain rate of post-treatment controls (PTC), regardless of treatment efficacy. Although the kinetics of HIV rebound should allow observing differences between placebo and control regarding the post treatment controls rate in case of efficacy of the IMPs, assessing the length and determinants of a post-intervention control (PIC) (i.e., associated with vaccination) beyond 24 weeks is crucial for developing a curative approach to HIV infection. In this regard, an extension of the ATI phase for those individuals with pVL less than 2,000 copies/mL after 24 weeks of ATI in the AELIX-002 offers an unique research opportunity to better understand relevant aspects of the mechanisms involved in the different phenotypes of a PIC and PTC.

This trial will enrol participants of the AELIX-002 clinical trial regardless of whether they received vaccines or placebo, who reach 24 weeks of ATI with pVL <2,000 cop/ml and are willing to remain off cART. After accepting participation, subjects will undergo a one-year extension [48 weeks] of ATI monitoring (total duration of ATI envisioned will be of 72 weeks [24 weeks in AELIX-002 study + 48 weeks in current study]), followed by 24 weeks of safety follow-up after cART is resumed.

The primary objective of this study is to assess the safety and durability of viral control after AELIX-002 clinical trial intervention beyond 6 months of ATI. Furthermore, the study will collect biological samples to be stored for further investigational studies.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Participants of the AELIX-002 clinical trial were randomly allocated to one of the following arms:

  • Vaccine: DNA.HTI at weeks 0, 4, and 8 and MVA.HTI at weeks 12 and 20 (DDDMM) followed by ChAdOx1.HTI at weeks 0 and 12 and MVA.HTI at week 24 (CCM), starting at least 24 weeks after MVA.HTI week 20.
  • Placebo: Normal saline solution at weeks 0, 4, 8, 12, and 20 (PPPPP) followed by normal saline solution at weeks 0, 12 and 24 (PPP), starting at least 24 weeks after week 20 administration.

ATI_extension will keep allocation from AELIX-002 for a separate description of the results.

Masking: Double (Participant, Investigator)
Masking Description: AELIX-002 was a double-blind clinical trial. During ATI_extension, AELIX-002 will be unblinded and allocation will be disclosed to both participants and investigators.
Primary Purpose: Other
Official Title: Study to Assess the Safety and Durability of Viral Control Beyond 24 Weeks of Analytical Treatment Interruption After the Administration of Candidate HIV-1 Vaccines DNA.HTI, MVA.HTI and ChAdOx1.HTI or Placebo in Early Treated HIV-1 Positive Individuals (ATI Extension of AELIX-002 Study)
Actual Study Start Date : June 1, 2020
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Vaccine group
ATI_extension will keep allocation from AELIX-002 for a separate description of the results.
Biological: Vaccine + extension of the ATI period
During the AELIX-002 trial participants received the following: DNA.HTI at weeks 0, 4, and 8 and MVA.HTI at weeks 12 and 20 (DDDMM) followed by ChAdOx1.HTI at weeks 0 and 12 and MVA.HTI at week 24 (CCM), starting at least 24 weeks after MVA.HTI week 20. After that, on ATI_extension trial, ATI will be extended for 48 weeks.

Placebo Comparator: Placebo group
ATI_extension will keep allocation from AELIX-002 for a separate description of the results.
Other: Placebo + extension of the ATI period
During the AELIX-002 trial participants received the following: Normal saline solution at weeks 0, 4, 8, 12, and 20 (PPPPP) followed by normal saline solution at weeks 0, 12 and 24 (PPP), starting at least 24 weeks after week 20 administration. After that, on ATI_extension trial, ATI will be extended for 48 weeks.




Primary Outcome Measures :
  1. Percentage of participants with viral remission [ Time Frame: week 72 ]
    Percentage of participants with viral remission, defined as plasma viral load (pVL) <50 copies/ml at 72 weeks after start of ATI.

  2. Percentage of participants with viral control [ Time Frame: week 72 ]
    Percentage of participants with viral control, defined as a pVL <2,000 copies/ml at 72?weeks after start of ATI.

  3. Time to viral detection [ Time Frame: up to 72weeks after start of ATI ]
    Time to viral detection up to 72 weeks after start of ATI, defined as the time from ATI start to first occurrence of detectable pVL (≥50 copies/ml).

  4. Time to viral rebound [ Time Frame: up to 72 weeks after start of ATI ]
    Time to viral rebound up to 72 weeks after start of ATI, defined as the time from ATI start to first occurrence of ≥ 2,000 copies/ml.

  5. Percentage of participants who remain off cART [ Time Frame: Week 72 ]
    Percentage of participants who remain off cART at 72 weeks after ATI start.

  6. Time off cART [ Time Frame: From ATI start to week 72 ]
    Time off cART, defined as time to cART resumption from ATI start.


Secondary Outcome Measures :
  1. Phenotypes characterization [ Time Frame: From ATI start to week 72 ]
    Different phenotypes will be characterized by the description of pVL and CD4 dynamics of each participant, and grouping according to their profile (non-rebounders, late-rebounders, post-rebound controllers, …).

  2. Change in a score for ATI psychological impact [ Time Frame: At weeks 24, 48 and at week 4 post cART resumption (or at the End of ATI visit in case of early withdrawal). ]
    Acceptability and the psychological impact of a longer ATI will be assessed by the change in a score of a questionnaire administered at weeks 24, 48 and at week 4 post cART resumption (or at the End of ATI visit in case of early withdrawal).

  3. The proportion of participants who develop symptoms compatible with acute retroviral syndrome. [ Time Frame: From ATI start to week 72 ]
    The proportion of participants who develop symptoms compatible with acute retroviral syndrome.

  4. The proportion of participants who suppress pVL to <50 copies/ml [ Time Frame: 24 weeks after cART resumption ]
    The proportion of participants who suppress pVL to <50 copies/ml 24 weeks after cART resumption

  5. The proportion of participants who develop new mutations not present in the pre-cART genotype [ Time Frame: 24 weeks after cART resumption ]
    The 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 24 weeks after cART resumption).

  6. Description of participants who develop AEs related to the prime- boost regimen during this extension of ATI period. [ Time Frame: From ATI_extension start to week 72 ]
    Description of participants who develop AEs related to the prime-boost regimen during this extension of ATI period.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants of the AELIX-002 clinical trial at week 24 of ATI:

    1. Willing to continue the ATI up to 1 year.
    2. With pVL <2,000 copies/ml at week 24 of ATI on the AELIX-002 study.
    3. CD4 count ≥350 cells/mm3 at week 24 of ATI on the AELIX-002study.
    4. Willing to comply with the measures to prevent HIV transmission and reinfection required by the protocol.
    5. Available for follow-up for the planned duration of the ATI period of this study.
    6. Willing to accept blood draws and collect stool at time points specified in the Schedule of Procedures.
    7. If heterosexually active female; using an effective method of contraception (hormonal contraception, intra-uterine device

      (IUD), or anatomical sterility in self or partner1) during the ATI and until her pVL is <50 copies/ml after cART resumption.

    8. If heterosexually active male; using 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

      sterility1) during the ATI and until his pVL is <50 copies/ml after cART resumption.

    9. Not willing to donate blood during the study.
    10. Participants who understand the information provided, in the opinion of the investigator.

      Exclusion Criteria:

    1- Pregnancy or breastfeeding.

    2. History or clinical manifestations of any physical or psychiatric disorder which could impair the subject's ability to complete the study.

    3. 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.

    4. Active hepatitis B or C at week 24 of ATI on the AELIX-002 study.

    5. Risk of HIV transmission (i.e. repeated STI during the AELIX-002 ATI period or reported unprotected anal sex).


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04385875


Contacts
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Contact: Beatriz Mothe Pujadas, PhD, MD 0034934657897 bmothe@irsicaixa.es

Locations
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Spain
Germans Trias i Pujol Hospital Recruiting
Badalona, Barcelona, Spain, 08916
Contact: BEATRIZ F MOTHE PUJADAS, MD,Phd    0034934657897    bmothe@irsicaixa.es   
Sponsors and Collaborators
Fundacio Lluita Contra la SIDA
Aelix Therapeutics
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Responsible Party: Fundacio Lluita Contra la SIDA
ClinicalTrials.gov Identifier: NCT04385875    
Other Study ID Numbers: ATI_extension
First Posted: May 13, 2020    Key Record Dates
Last Update Posted: July 23, 2020
Last Verified: July 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Fundacio Lluita Contra la SIDA:
HIV-1 infection
Therapeutic Vaccines
HTI
Antiretroviral Treatment Interruption (ATI)
Viral control
Additional relevant MeSH terms:
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Infection