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

NCT03204617 | Completed Phase 1 DMC

• 1 other identifier: AELIX-002
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HIV

Keywords

HIV infection; First in Human; Therapeutic Vaccines; HTI; HIV reservoir

Outcome Measures

Primary Outcomes (2)

• 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

  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

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

Secondary Outcomes (12)

• Proportion of participants that develop T cell responses to HTI-encoded regions

  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

  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

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

• 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)

  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

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

Study Arms (2)

DDDMM + CCM

EXPERIMENTAL

DNA.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.

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)

Placebo

PLACEBO COMPARATOR

0.9% 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.

Drug: Placebo

Interventions

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

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

Also known as: N/H

DDDMM + CCM

At least 24 weeks since DDDMM, ChAdOx1.HTI 0.5mL at weeks 0 and 12 + MVA.HTI 0.5mL at week 24 (CCM) BIOLOGICAL

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.

Also known as: N/H

DDDMM + CCM

Placebo DRUG

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

Also known as: N/H

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• Aelix Therapeutics: lead

Study Sites (1)

IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Related Publications (1)

• 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.

  PMID: 36302893 DERIVED

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Beatriz Mothe, MD, PhD

  IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double Blind: two or more parties are unaware of the intervention assignment
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2017
• First Posted: July 2, 2017
• Study Start: July 7, 2017
• Primary Completion: July 1, 2020
• Study Completion: March 10, 2021
• Last Updated: April 8, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)