Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03204617
Recruitment Status : Active, not recruiting
First Posted : July 2, 2017
Last Update Posted : June 6, 2019
Sponsor:
Information provided by (Responsible Party):
Aelix Therapeutics

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.

Condition or disease Intervention/treatment Phase
HIV Biological: DNA.HTI 4 mg at weeks 0, 4 and 8 + MVA.HTI 2x10^8pfu at weeks 12 and 20 (DDDMM) Biological: At least 24 weeks since DDDMM, ChAdOx1.HTI 5x10^10 Vp at weeks 0 and 12 + MVA.HTI 2x10^8pfu at week 24 (CCM) Drug: Placebo Phase 1

Detailed Description:

AELIX Therapeutics in collaboration with IrsiCaixa has developed a novel immunogen, termed HTI which was designed as an immunogen for T cells 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. HTI is a chemically synthesized chimeric protein consisting of 16 continuous segments of HIV-1 each between 11 and 78 amino acids in length and encoding critical targets of viral proteins Gag (45%), Pol (44%), Vif (8%) and Nef (3%). The function of the immunogen HTI is the induction of an immune response by HIV-1-specific T cells directed against the regions included in the insert HTI, which can control HIV-1 effectively. The HTI immunogen is administered through an heterologous prime-boost vaccination that includes three components, a DNA vaccine prime (DNA.HTI), a viral vaccine boost (MVA.HTI and ChAdOx1.HTI).

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 patients on suppressive antiretroviral treatment who started Combination Antiretroviral Therapy (cART) within first 6 months of confirmed HIV-1 acquisition. In Phase A, patients will be randomized to receive active vaccine or placebo in a double blinded fashion. There will be a sentinel group of three patients; two will receive active vaccine and one will receive placebo (0.9% normal saline). During the sentinel phase of the study only one patient will be 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 individuals, six of the remaining cohort will be enrolled (in blocks of 3 patients per day) and the final six patients one week later, also in blocks of 3 patients per day. On each vaccination day, 2 patients will receive active IMP and 1 will receive 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 will be performed to further include 30 participants (Group 3). Participants will be recruited sequentially and without following blocks of pre-defined number of vaccinees and placebos per immunization day.

At week 32, all participants will be 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. No interventions are envisioned during this extension Roll-over Phase.

After a favourable SMC report, transition to Phase C will be allowed. During Roll-over Phase participants in Phase A/B will be 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 will remain 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double Blind: two or more parties are unaware of the intervention assignment
Primary Purpose: Basic Science
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
Actual Study Start Date : July 7, 2017
Estimated Primary Completion Date : January 31, 2020
Estimated Study Completion Date : September 30, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: DDDMM + CCM
DNA.HTI 4 mg at weeks 0, 4 and 8 + MVA.HTI 2x10^8pfu at weeks 12 and 20. At least 24 weeks since second MVA.HTI administration (week 20), administration of ChAdOx1.HTI 5x10^10 Vp at weeks 0 and 12 + MVA.HTI 2x10^8pfu at week 24.
Biological: DNA.HTI 4 mg at weeks 0, 4 and 8 + MVA.HTI 2x10^8pfu at weeks 12 and 20 (DDDMM)
Vaccine DNA.HTI 4 mg at weeks 0, 4 and 8 + Vaccine MVA.HTI 2x10^8pfu at weeks 12 and 20 (DDDMM).
Other Name: N/H

Biological: At least 24 weeks since DDDMM, ChAdOx1.HTI 5x10^10 Vp at weeks 0 and 12 + MVA.HTI 2x10^8pfu at week 24 (CCM)
At least 24 weeks since second MVA.HTI administration (week 20), administration of ChAdOx1.HTI 5x10^10 Vp at weeks 0 and 12 + MVA.HTI 2x10^8pfu at week 24.
Other Name: N/H

Placebo Comparator: Placebo
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
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
Other Name: N/H




Primary Outcome Measures :
  1. Proportion of patients 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 ]
    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

  2. Proportion of patients that develop Grade 3 or 4 systemic reactions [ Time Frame: From first DNA.HTI/Placebo administration to week 32 and from first ChAdOx1.HTI/Placebo administration to week 32 ]
    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


Secondary Outcome Measures :
  1. Proportion of patients that develop de-novo T cell responses to HTI-encoded regions [ Time Frame: From first DNA.HTI/Placebo administration to week 32 and from first ChAdOx1.HTI/Placebo administration to week 32 ]
    Proportion of patients that develop de-novo T cell responses to HTI-encoded regions as determined by IFN-γ ELISPOT assay in vaccine and placebo recipients

  2. Breadth of total vaccine induced HIV-specific responses [ 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 measured IFN-γ ELISPOT in vaccine and placebo recipients

  3. Magnitude of total vaccine induced HIV-specific responses [ 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 measured IFN-γ ELISPOT in vaccine and placebo recipients

  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) [ 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 viral remission, defined as plasma viral load (pVL) <50 copies/mL 12 and 24 weeks after start of ATI

  5. Percentage of participants with viral control, defined as a 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). ]
    Percentage of participants with viral control, defined as a pVL <2,000 copies/mL at 12 and 24 weeks after start of ATI

  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 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 detection, defined as the time from ATI start (visit Phase C week 32) to first occurrence of detectable pVL (>50 copies/mL).

  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 Frame: From ATI start (visit Phase C week 32) to first occurrence of pVL >10,000 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.

  8. 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). ]
    Percentage of participants who remain off cART at 12 and 24 weeks after ATI (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 Frame: From ATI start (visit Phase C week 32) to cART resumption through study completion, up to week 68 ]
    Time off cART, defined as time to cART resumption since ATI start (visit Phase C week 32).

  10. 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 symptoms compatible with acute retroviral syndrome (ARS) during ATI.

  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). [ 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).

  12. Proportion of participants who suppress pVL to <50 copies/mL 12 weeks after cART resumption. [ Time Frame: 12 weeks after cART resumption. ]
    Proportion of participants who suppress pVL to <50 copies/mL 12 weeks after cART resumption.



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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Confirmed HIV-1 infection
  2. On combined antiretroviral treatment (defined as ≥ 3 antiretroviral drugs) initiated within 6 months of estimated time of HIV-1 acquisition.
  3. Willing and able to be adherent to their cART regimen for the duration of the study.
  4. 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 (<200 cop/ml, non-consecutive, representing <10% total determinations).
  5. Being on the same cART regimen for at least 4 weeks at screening visit.
  6. 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).
  7. Stable CD4 counts ≥ 400 cells per mm^3 for the last 6 months at screening visit.
  8. Availability of stored biological sample (including PBMC and plasma) before any cART initiation.
  9. Aged at least 18 years on the day of screening and no greater than 60 years on the day of the first vaccination.
  10. Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study.
  11. In the opinion of the principal investigator or designee, the patient has understood the information provided and capable of giving written informed consent.
  12. 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.
  13. 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.
  14. Willing to accept blood draws and collect stool at time points specified in the Schedule of Procedures.
  15. Willing to forgo donating blood during the study.

Exclusion Criteria:

  1. Pregnancy or lactating.
  2. Presence of resistance drug mutations in a pre-cART genotype.
  3. Reported periods of suboptimal adherence to cART.
  4. History of past antiretroviral treatment interruptions longer than 2 weeks.
  5. Participation in another clinical trial within 12 weeks of study entry (at screening visit).
  6. Any AIDS-defining disease or progression of HIV-related disease.
  7. History of autoimmune disease.
  8. History or clinical manifestations of any physical or psychiatric disorder which could impair the subject's ability to complete the study.
  9. Receipt of approved vaccines within 2 weeks of study entry and along the duration of the trial.
  10. History of anaphylaxis or severe adverse reaction to vaccines.
  11. Previous immunisation with any experimental immunogens.
  12. Receipt of blood products within 6 months of study entry.
  13. Treatment for cancer or lymphoproliferative disease within 1 year of study entry.
  14. 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.
  15. 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).
  16. Any laboratory abnormalities including:

    Haematology

    • Haemoglobin < 10.0 g/dl
    • Absolute Neutrophil Count (ANC) ≤ 1,000 /mm3 (≤ 1 x 109 /l)
    • Absolute Lymphocyte Count (ALC) ≤ 600 /mm3 (≤ 0.6 x 109 /l)
    • Platelets ≤100,000 /mm3, ≥ 550,000 /mm3 (≤ 100 /l, ≥ 550 /l)

    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
  17. Complete refusal to cART interruption

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): NCT03204617


Locations
Layout table for location information
Spain
IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, Spain, 08916
Sponsors and Collaborators
Aelix Therapeutics
Investigators
Layout table for investigator information
Principal Investigator: Beatriz Mothe, MD, PhD IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol

Layout table for additonal information
Responsible Party: Aelix Therapeutics
ClinicalTrials.gov Identifier: NCT03204617    
Other Study ID Numbers: AELIX-002
First Posted: July 2, 2017    Key Record Dates
Last Update Posted: June 6, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Aelix Therapeutics:
HIV infection
First in Human
Therapeutic Vaccines
HTI
HIV reservoir