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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

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ClinicalTrials.gov Identifier: NCT02616874
Recruitment Status : Completed
First Posted : November 30, 2015
Last Update Posted : January 17, 2018
Sponsor:
Collaborators:
Germans Trias i Pujol Hospital
Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
Hospital Clinic of Barcelona
Hospital de Sant Pau
HIVACAT
University of Oxford
BCN Checkpoint
Information provided by (Responsible Party):
IrsiCaixa

Tracking Information
First Submitted Date  ICMJE November 9, 2015
First Posted Date  ICMJE November 30, 2015
Last Update Posted Date January 17, 2018
Study Start Date  ICMJE February 2016
Actual Primary Completion Date September 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 30, 2015)
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: November 25, 2015)
  • Number of participants with grade >=3 adverse events assessed by DAIDS granding 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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 4, 2015)
  • 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). ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 25, 2015)
  • Romidepsin Cmax [ Time Frame: week 3 ]
    RMD plasma concentrations will be measured by 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 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 ]
  • IFNg production assessed by ELISPOT and after PBMC stimulation with HIVconsv-specific peptides [ 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 pVL <2,000 cpies/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). ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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)
Brief Summary 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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV
Intervention  ICMJE
  • 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
Study Arms  ICMJE Experimental: MVA.HIVconsv plus romidepsin
MVA.HIVconsv plus romidepsin
Interventions:
  • Drug: MVA.HIVconsv vaccine
  • Drug: Romidepsin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 14, 2016)
15
Original Estimated Enrollment  ICMJE
 (submitted: November 25, 2015)
24
Actual Study Completion Date  ICMJE October 30, 2017
Actual Primary Completion Date September 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02616874
Other Study ID Numbers  ICMJE BCN02-Romi
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party IrsiCaixa
Study Sponsor  ICMJE IrsiCaixa
Collaborators  ICMJE
  • Germans Trias i Pujol Hospital
  • Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
  • Hospital Clinic of Barcelona
  • Hospital de Sant Pau
  • HIVACAT
  • University of Oxford
  • BCN Checkpoint
Investigators  ICMJE Not Provided
PRS Account IrsiCaixa
Verification Date January 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP