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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT03204617
First Posted: July 2, 2017
Last Update Posted: October 6, 2017
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.
Information provided by (Responsible Party):
Aelix Therapeutics
  Purpose
The AELIX-002 study aims to evaluate the safety and the immunogenicity of DNA.HTI administered alone and as part of an heterologous prime-boost regimen in combination with MVA.HTI in early diagnosed and treated HIV-1 positive individuals, males and females,18-50 years of age.

Condition Intervention Phase
HIV Biological: DNA.HTI 4 mg and MVA.HTI 2x10^8pfu vaccines Drug: Placebo Phase 1

Study Type: Interventional
Study Design: 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 and MVA.HTI in Early Treated HIV-1 Positive Individuals

Resource links provided by NLM:


Further study details as provided by Aelix Therapeutics:

Primary Outcome Measures:
  • Proportion of patients that develop Grade 3 or 4 local reactions [ Time Frame: From baseline 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

  • Proportion of patients that develop Grade 3 or 4 systemic reactions [ Time Frame: From baseline 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:
  • Proportion of patients that develop de-novo T cell responses to HTI-encoded regions [ Time Frame: Baseline 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

  • Breadth of total vaccine induced HIV-specific responses [ Time Frame: Baseline to week 32 ]
    Breadth of total vaccine induced HIV-specific responses measured IFN-γ ELISPOT in vaccine and placebo recipients

  • Magnitude of total vaccine induced HIV-specific responses [ Time Frame: Baseline to week 32 ]
    Magnitude of total vaccine induced HIV-specific responses measured IFN-γ ELISPOT in vaccine and placebo recipients


Estimated Enrollment: 15
Actual Study Start Date: July 7, 2017
Estimated Study Completion Date: May 2018
Estimated Primary Completion Date: February 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DNA.HTI 4 mg + MVA.HTI 2x10^8pfu
DNA.HTI 4 mg + MVA.HTI 2x10^8pfu at 0, 4, 8, 12 and 20
Biological: DNA.HTI 4 mg and MVA.HTI 2x10^8pfu vaccines
Vaccine DNA.HTI 4 mg at weeks 0, 4 and 8 + Vaccine MVA.HTI 2x10^8pfu at weeks 12 and 20.
Other Name: N/H
Placebo Comparator: Placebo
0.9% sterile normal saline solution at weeks 0, 4, 8, 12 and 20.
Drug: Placebo
0.9% sterile normal saline solution at weeks 0, 4, 8, 12 and 20.
Other Name: N/H

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 two components, a DNA vaccine prime (DNA.HTI) and a viral vaccine boost (MVA.HTI).

The AELIX-002 Phase 1 study will evaluate the safety and immunogenicity of both the DNA.HTI and MVA.HTI vaccines in HIV-1 positive patients on suppressive antiretroviral treatment who started cART within first 6 months of confirmed HIV-1 acquisition. 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).

  Eligibility

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.


Ages Eligible for Study:   18 Years to 50 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 ≥ 500 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 50 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.

    • condom use nor diaphragma are considered as an additional method of contraception only and cannot be the only method of contraception used as not been considered an effective method by the Clinical Trial Facilitation Group (CTFG) guidelines.

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 (≤ 1 x 109 /l)
  • Platelets ≤100,000 /mm3, ≥ 550,000 /mm3 (≤ 90 /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. Small-pox vaccination.

  • Clinical evidence of vaccinia scarification or self-reported history of vaccinia vaccination.

    • Efforts will be made to ensure all patients AELIX-002 are updated on their Hepatitis A, Hepatitis B and Pneumococcal vaccinations before enrollment. Patients willing to undergo seasonal Flu vaccinations will be excluded if vaccination would be expected to occur throughout the duration of the trial.
  Contacts and Locations
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
Spain
IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, Spain, 08916
Sponsors and Collaborators
Aelix Therapeutics
  More Information

Responsible Party: Aelix Therapeutics
ClinicalTrials.gov Identifier: NCT03204617     History of Changes
Other Study ID Numbers: AELIX-002
First Submitted: June 13, 2017
First Posted: July 2, 2017
Last Update Posted: October 6, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Additional relevant MeSH terms:
Vaccines
Immunologic Factors
Physiological Effects of Drugs