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Study to Evaluate the Safety and Effect of HIVconsv Vaccines in Combination With Histone Deacetylase Inhibitor Romidepsin on the Viral Rebound Kinetic After Treatment Interruption in Early Treated HIV-1 Infected Individuals

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Germans Trias i Pujol Hospital
Fundacio Lluita Contra la SIDA
Hospital Clinic of Barcelona
Hospital de Sant Pau
HIVACAT
University of Oxford
BCN-Checkpoint
Information provided by (Responsible Party):
IrsiCaixa
ClinicalTrials.gov Identifier:
NCT02616874
First received: November 9, 2015
Last updated: December 14, 2016
Last verified: December 2016
  Purpose
The BCN02-Romi study aims to evaluate a combined "kick and kill" strategy using the most immunogenic candidate vaccine available so far (HIVconsv) with the strongest latency reversal agent available at present time (romidepsin) in a cohort of early-treated HIV positive individuals.

Condition Intervention Phase
HIV Drug: MVA.HIVconsv vaccine Drug: Romidepsin Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Phase I Trial to Evaluate the Safety and Effect of HIVconsv Vaccines in Combination With Histone Deacetylase Inhibitor Romidepsin on the Viral Rebound Kinetic After Treatment Interruption in Early Treated HIV-1 Infected Individuals (BCN02-Romi)

Resource links provided by NLM:


Further study details as provided by IrsiCaixa:

Primary Outcome Measures:
  • Number of participants with grade >=3 adverse events assessed by Division of AIDS (DAIDS) grading table [ Time Frame: Through study completion, maximum 75 weeks ]
    Grade >=3 adverse events

  • Number of participants with serious adverse events [ Time Frame: Through study completion, maximum 75 weeks ]
    Serious adverse events

  • Viral reservoir measured by total HIV-1 DNA copies per 10e6 CD4+ T cells [ Time Frame: From baseline to visit week 6 (romidepsin 3 + 1 week) ]
    Total HIV-1 DNA copies per 10e6 CD4+ T cells


Secondary Outcome Measures:
  • Romidepsin Cmax [ Time Frame: week 3 ]
    RMD plasma concentrations will be measured by Liquid chromatography-mass spectrometry (LC-MS/MS)

  • Romidepsin Cmax [ Time Frame: week 4 ]
    RMD plasma concentrations will be measured by LC-MS/MS

  • Romidepsin Cmax [ Time Frame: week 5 ]
    RMD plasma concentrations will be measured by LC-MS/MS

  • Romidepsin Cmin [ Time Frame: week 3 ]
    RMD plasma concentrations will be measured by LC-MS/MS

  • Romidepsin Cmin [ Time Frame: week 4 ]
    RMD plasma concentrations will be measured by LC-MS/MS

  • Romidepsin Cmin [ Time Frame: week 5 ]
    RMD plasma concentrations will be measured by LC-MS/MS

  • Romidepsin area under curve (AUC) [ Time Frame: week 3 ]
    RMD plasma concentrations will be measured by LC-MS/MS

  • Romidepsin AUC [ Time Frame: week 4 ]
    RMD plasma concentrations will be measured by LC-MS/MS

  • Romidepsin AUC [ Time Frame: week 5 ]
    RMD plasma concentrations will be measured by LC-MS/MS

  • HIV-1 expression in resting CD4+ T-cells measured by CA-RNA and single-copy assay (SCA) [ Time Frame: week 6 ]
  • Levels of Histone H3 acetylation in lymphocytes [ Time Frame: week 6 ]
  • CTL toxicity assessment based on viability, activation or exhaustion (most relevant marker according to previous studies) [ Time Frame: week 6 ]
  • HIVconsv-specific T cell responses will be measured by IFNg ELISPOT using peptide pools covering different HIV proteins and HIVcons sequences. [ Time Frame: week 6 ]
  • Viral suppressive capacity of CD8+ T cells in vitro, using a flow cytometric assay [ Time Frame: Baseline ]
  • Viral suppressive capacity of CD8+ T cells in vitro, using a flow cytometric assay [ Time Frame: Week 17 ]
  • Proportion of individuals who initiate a MAP following the futility analysis [ Time Frame: Week 17 ]
  • Proportion of individuals who maintain sustained plasma viral load (pVL) <2,000 copies/ml [ Time Frame: Week 29 ]
  • Proportion of individuals in whom cART is reinitiated due to viral rebound [ Time Frame: Up to 51 weeks ]
  • Emergence of viral resistance during MAP phase [ Time Frame: Up to 51 weeks ]
    Description of viral resistance emerged, genotype.

  • Proportion of patients with viral suppression 6 months after treatment resumption. [ Time Frame: 24 weeks after treatment resumption (up to 75 weeks). ]

Estimated Enrollment: 15
Study Start Date: February 2016
Estimated Study Completion Date: October 2017
Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MVA.HIVconsv plus romidepsin
MVA.HIVconsv plus romidepsin
Drug: MVA.HIVconsv vaccine
Dose: 2x10e8 pfu, Interval: weeks 0 and 9.
Drug: Romidepsin
Dose: 5mg/m2 over 4hours, Interval: weeks 3, 4 and 5

Detailed Description:
The combined use of therapeutic vaccination and specific drugs that can reactivate latent virus from the reservoir (Kick and kill strategies) hold the promise to achieve functional cure and viral eradication of HIV infection. The present project consists of a proof-of-concept clinical trial in a cohort of 24 early treated HIV-1 infected individuals rolled-over from the BCN01 vaccine clinical trial in which participants received the most immunogenic vaccines tested to date, ChAd and modified vaccinia Ankara (MVA).HIVconsv vaccines. All individuals will be given a booster immunization with MVA.HIVconsv in combination with romidepsin (RMD), a potent histone deacetylation inhibitor (HDACi) and will later undergo a monitored antiretroviral pause. HIVconsv vaccines have specifically been designed to stimulate a broad and potent cytotoxic T cell (CTL) response towards the most conserved viral regions of the HIV-1 proteome, which have recently been suggested to have a crucial role when targeting HIV variants harboured in the latent reservoir with mutations to escape T-cell immune responses. The study includes the development of a population pharmacokinetic/pharmacodynamic (PK/PD) substudy to analyse the in vivo effects of RMD in the induction of HIV expression in resting cells, deeply investigate any unintended effect on the CTL function as well as predict the relationship between RMD exposure and such effects. The investigators' results will allow investigators to optimize RMD dosing, to evaluate the clinical efficacy of this eradication strategy after the cART interruption and to identify better correlates of control of rebound viremia after cessation of treatment.
  Eligibility

Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject included in ChAd-MVA.HIVconsv_BCN01 study with complete follow-up and included in BCN01-RO extension study.
  2. Optimal virological suppression for at least 3 years.cop/ml).
  3. Being on a non-boosted integrase-inhibitor based regimen (raltegravir or dolutegravir) for at least 4 weeks at screening visit.
  4. Haematological and biochemical laboratory parameters as follows:

    • Haemoglobin > 10g/dl
    • Platelets > 100.000/dl
    • Alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)
    • Creatinine ≤ 1.3 x ULN
  5. CD4 T cell count ≥500 cells/mm3

Exclusion Criteria:

  1. Positive pregnancy test.
  2. Presence of resistance drug mutations in the screening genotype
  3. History of autoimmune disease other than HIV-related auto-immune disease.
  4. Treatment for cancer or lymphoproliferative disease within 1 year of study entry
  5. Any other prior therapy which, in the opinion of the investigators, would make the individual unsuitable for the study or influence the results of the study
  6. Current or recent use (within last 3 months) of interferon or systemic corticosteroids or other immunosuppressive agents
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02616874

Locations
Spain
Germans Trias i Pujol Hospital
Badalona, Barcelona, Spain, 08916
Clinic Hospital
Barcelona, Spain, 08036
Sponsors and Collaborators
IrsiCaixa
Germans Trias i Pujol Hospital
Fundacio Lluita Contra la SIDA
Hospital Clinic of Barcelona
Hospital de Sant Pau
HIVACAT
University of Oxford
BCN-Checkpoint
  More Information

Responsible Party: IrsiCaixa
ClinicalTrials.gov Identifier: NCT02616874     History of Changes
Other Study ID Numbers: BCN02-Romi
Study First Received: November 9, 2015
Last Updated: December 14, 2016

Keywords provided by IrsiCaixa:
HIV infection
Early treatment
Romidepsin
HDACi
Therapeutic Vaccines
HIVconsv
HIV reservoir
Population PK/PD analysis

Additional relevant MeSH terms:
Vaccines
Romidepsin
Histone Deacetylase Inhibitors
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 27, 2017