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)

NCT04385875 | Completed Phase 1

• 1 other identifier: ATI_extension
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV-1 Infection

Keywords

HIV-1 infection; Therapeutic Vaccines; HTI; Antiretroviral Treatment Interruption (ATI); Viral control

Outcome Measures

Primary Outcomes (6)

• Percentage of participants with viral remission

  Percentage of participants with viral remission, defined as plasma viral load (pVL) \<50 copies/ml at 72 weeks after start of ATI.

  week 72

• Percentage of participants with viral control

  Percentage of participants with viral control, defined as a pVL \<2,000 copies/ml at 72?weeks after start of ATI.

  week 72

• Time to viral detection

  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).

  up to 72weeks after start of ATI

• Time to viral rebound

  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.

  up to 72 weeks after start of ATI

• Percentage of participants who remain off cART

  Percentage of participants who remain off cART at 72 weeks after ATI start.

  Week 72

• Time off cART

  Time off cART, defined as time to cART resumption from ATI start.

  From ATI start to week 72

Secondary Outcomes (6)

• Phenotypes characterization

  From ATI start to week 72

• Change in a score for ATI psychological impact

  At weeks 24, 48 and at week 4 post cART resumption (or at the End of ATI visit in case of early withdrawal).

• The proportion of participants who develop symptoms compatible with acute retroviral syndrome.

  From ATI start to week 72

• The proportion of participants who suppress pVL to <50 copies/ml

  24 weeks after cART resumption

• The proportion of participants who develop new mutations not present in the pre-cART genotype

  24 weeks after cART resumption

Study Arms (2)

Vaccine group

EXPERIMENTAL

ATI\_extension will keep allocation from AELIX-002 for a separate description of the results.

Biological: Vaccine + extension of the ATI period

Placebo group

PLACEBO COMPARATOR

ATI\_extension will keep allocation from AELIX-002 for a separate description of the results.

Other: Placebo + extension of the ATI period

Interventions

Vaccine + extension of the ATI period BIOLOGICAL

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.

Vaccine group

Placebo + extension of the ATI period OTHER

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.

Placebo group

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Participants of the AELIX-002 clinical trial at week 24 of ATI:
• Willing to continue the ATI up to 1 year.
• With pVL \<2,000 copies/ml at week 24 of ATI on the AELIX-002 study.
• CD4 count ≥350 cells/mm3 at week 24 of ATI on the AELIX-002study.
• Willing to comply with the measures to prevent HIV transmission and reinfection required by the protocol.
• Available for follow-up for the planned duration of the ATI period of this study.
• Willing to accept blood draws and collect stool at time points specified in the Schedule of Procedures.
• 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.
• 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.
• Not willing to donate blood during the study.
• Participants who understand the information provided, in the opinion of the investigator.

You may not qualify if:

• Pregnancy or breastfeeding.
• \. History or clinical manifestations of any physical or psychiatric disorder which could impair the subject's ability to complete the study.
• \. 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.
• \. Active hepatitis B or C at week 24 of ATI on the AELIX-002 study.
• \. Risk of HIV transmission (i.e. repeated STI during the AELIX-002 ATI period or reported unprotected anal sex).

Sponsors & Collaborators

• Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia: lead
• Aelix Therapeutics: collaborator

Study Sites (1)

Germans Trias i Pujol Hospital

Badalona, Barcelona, 08916, Spain

Location

MeSH Terms

Interventions

Vaccines

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 8, 2020
• First Posted: May 13, 2020
• Study Start: June 1, 2020
• Primary Completion: August 30, 2021
• Study Completion: February 10, 2022
• Last Updated: May 4, 2022

Record last verified: 2022-05

Locations

ES (1)