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

May 6, 2024 updated by: IrsiCaixa

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)

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
15

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Barcelona, Spain, 08036
        • Clinic Hospital
    • Barcelona
      • Badalona, Barcelona, Spain, 08916
        • Germans Trias i Pujol Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 95 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
Through study completion, maximum 75 weeks
Number of participants with serious adverse events
Time Frame: Through study completion, maximum 75 weeks
Serious adverse events
Through study completion, maximum 75 weeks
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
From baseline to visit week 6 (romidepsin 3 + 1 week)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Romidepsin Cmax
Time Frame: week 3
RMD plasma concentrations will be measured by Liquid chromatography-mass spectrometry (LC-MS/MS)
week 3
Romidepsin Cmax
Time Frame: week 4
RMD plasma concentrations will be measured by LC-MS/MS
week 4
Romidepsin Cmax
Time Frame: week 5
RMD plasma concentrations will be measured by LC-MS/MS
week 5
Romidepsin Cmin
Time Frame: week 3
RMD plasma concentrations will be measured by LC-MS/MS
week 3
Romidepsin Cmin
Time Frame: week 4
RMD plasma concentrations will be measured by LC-MS/MS
week 4
Romidepsin Cmin
Time Frame: week 5
RMD plasma concentrations will be measured by LC-MS/MS
week 5
Romidepsin area under curve (AUC)
Time Frame: week 3
RMD plasma concentrations will be measured by LC-MS/MS
week 3
Romidepsin AUC
Time Frame: week 4
RMD plasma concentrations will be measured by LC-MS/MS
week 4
Romidepsin AUC
Time Frame: week 5
RMD plasma concentrations will be measured by LC-MS/MS
week 5
HIV-1 expression in resting CD4+ T-cells measured by CA-RNA and single-copy assay (SCA)
Time Frame: week 6
week 6
Levels of Histone H3 acetylation in lymphocytes
Time Frame: week 6
week 6
CTL toxicity assessment based on viability, activation or exhaustion (most relevant marker according to previous studies)
Time Frame: week 6
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
week 6
Viral suppressive capacity of CD8+ T cells in vitro, using a flow cytometric assay
Time Frame: Baseline
Baseline
Viral suppressive capacity of CD8+ T cells in vitro, using a flow cytometric assay
Time Frame: Week 17
Week 17
Proportion of individuals who initiate a MAP following the futility analysis
Time Frame: Week 17
Week 17
Proportion of individuals who maintain sustained plasma viral load (pVL) <2,000 copies/ml
Time Frame: Week 29
Week 29
Proportion of individuals in whom cART is reinitiated due to viral rebound
Time Frame: Up to 51 weeks
Up to 51 weeks
Emergence of viral resistance during MAP phase
Time Frame: Up to 51 weeks
Description of viral resistance emerged, genotype.
Up to 51 weeks
Proportion of patients with viral suppression 6 months after treatment resumption.
Time Frame: 24 weeks after treatment resumption (up to 75 weeks).
24 weeks after treatment resumption (up to 75 weeks).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
IrsiCaixa

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Hospital Clinic of Barcelona
University of Oxford
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 de Sant Pau
HIVACAT
BCN Checkpoint

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 30, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 9, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 25, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 30, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 7, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 6, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • BCN02-Romi

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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