Therapeutic Intensification Plus Immunomodulation to Decrease the HIV-1 Viral Reservoir (EraMune02)

September 10, 2014 updated by: Robert L. Murphy

Multicenter, Randomized, Non-comparative, Controlled Study of Therapeutic Intensification Plus Immunomodulation in HIV-infected Patients With Long-term Viral Suppression

The objective of this study is to discover a new approach in which human immunodeficiency virus (HIV) can be eradicated from an infected individual by intensified antiretroviral treatment coupled with immunomodulation. The hypothesis is that eradication is possible only if very potent antiretroviral drugs are delivered in conjunction with an immunomodulatory agent that simultaneously attack the viral reservoirs.

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 objective of this study is to measure the impact of immunomodulation plus treatment intensification on the HIV reservoir in HIV-infected patients who have viral suppression on combination antiretroviral therapy. Treatment regimens first will be intensified by the addition of raltegravir and maraviroc for 8 week followed by immunomodulation with the NIH HIV-rAd5 vaccine plus DNA prime-boost for 24 weeks. The primary endpoint is measurement of change in peripheral cellular HIV DNA. A decrease of 0.5 log is considered significant. A secondary endpoints include change in HIV DNA in the rectal mucosa, immunologic changes in the peripheral blood and safety.

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.
28

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 2

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

  • United States
    • California
      • San Francisco, California, United States, 94110
        • University of California San Francisco
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
    • New York
      • New York, New York, United States, 10011
        • Cornell University

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

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • HIV-1 infection
  • At least 3 years of ART without interruption (less than one month cumulative)
  • ART regimen unchanged in the 3 months prior to screening
  • One HIV plasma viral load (RNA) documented at least 3 years prior to entry, and at least 2 HIV plasma viral load (RNA) documented per year thereafter
  • HIV plasma viral load (RNA) ≤ 500 copies/mL at least 3 years prior to entry, and HIV plasma viral load < 500 copies/mL for >90% of the measures thereafter
  • HIV plasma viral load (RNA) below the limit of detection for all values within the past year (one virologic blip allowed)
  • HIV plasma viral load below the limit of detection within 60 days of entry
  • CD4+ count ≥ 350 cells/mm3 within 60 days of entry
  • Proviral DNA ≥10 and ≤1000 copies/106 PBMCs within 75 days of entry
  • Adeno5 neutralizing antibody titers of 250 or less within 75 days of entry
  • Hemoglobin ≥ 10 g/dL within 60 days of entry
  • Platelets ≥ 100,000 per microliter within 60 days of entry
  • Hepatic transaminases (ALT and AST) ≤ 2.5 x ULN within 60 days of entry
  • Creatinine clearance > 50 mL/min by the Cockcroft-Gault equation within 60 days of entry

Exclusion Criteria:

  • Sexually active men and women who will not practice at least one form of barrier birth control (male partner using condoms, female partner using condoms, other barrier contraception, etc)
  • Pregnancy
  • Inability or unwillingness to provide informed consent
  • HBsAg positive
  • HCV antibody positive or HCV RNA detectable
  • Previous use of an integrase inhibitor (ie raltegravir) or a CCR5 inhibitor (ie maraviroc, vicriviroc). Use of raltegravir for non-treatment failure indications such as intensification or toxicity switches is allowed.
  • Immunologic therapeutic intervention (e.g. IL-2) within the past year
  • Participation in another clinical drug or device trial where the last dose of drug was within the past 30 days or an investigational medical device is currently implanted
  • Diagnosis of cancer within the last 5 years (except basal cell cutaneous cancers and cutaneous KS not requiring systemic therapy)
  • Co-morbid condition with an expected survival of less than 12 months
  • History of hypersensitivity to vaccination
  • History of autoimmune disease, such as systemic lupus erythematosis (SLE) or Hashimoto's thyroiditis
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements

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: Randomized
  • Interventional Model: Parallel 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.
Active Comparator: Maraviroc + raltegravir intensification
ART Intensification (addition of raltegravir and maraviroc to suppressive ART for 56 weeks)
Drug: ART intensification (raltegravir)
raltegravir 400 mg PO BID for 56 weeks
Other Names:
  • Isentress
Drug: ART intensification (maraviroc)
maraviroc 150, 300, or 600 mg PO BID (depending on PK interactions with other medications) for 56 weeks
Other Names:
  • Celsentri
  • Selzentry
Experimental: Maraviroc + raltegravir intens. plus DNA + HIV-rAd5 vaccine
ART Intensification (addition of raltegravir and maraviroc for 56 weeks) PLUS immunomodulation therapy with DNA prime vaccine (Weeks 8,12,16) + HIV-recombinant Ad5-based vaccine (Week 32)
Drug: ART intensification (raltegravir)
raltegravir 400 mg PO BID for 56 weeks
Other Names:
  • Isentress
Drug: ART intensification (maraviroc)
maraviroc 150, 300, or 600 mg PO BID (depending on PK interactions with other medications) for 56 weeks
Other Names:
  • Celsentri
  • Selzentry
Biological: DNA + HIV-rAd5 vaccine
4 mg subcutaneous injection at weeks 8 (DNA prime), 12 (DNA prime), 16 (DNA prime), and 32 (HIV-rAd5)

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
Time Frame
Change From Baseline in HIV DNA in PBMCs at Week 56
Time Frame: 56 weeks
56 weeks

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
Change From Baseline in HIV DNA in Rectal Tissue at Week 56
Time Frame: Week 56
Week 56
Change From Baseline in CD4+ T Cell Count at Week 56
Time Frame: Week 56
Week 56
HIV Specific T-cell Response to Env
Time Frame: 36 weeks
HIV-specific immunity: Interferon gamma ELISpot response to Env (clades A) at week 36 (one month after rAd5 boosting)
36 weeks
Serious Adverse Events Attributed to Study Treatments
Time Frame: 56 weeks
Grade 3 or 4 serious adverse events related to study treatments (raltegravir, maraviroc, or HIV-recombinant Ad5-based vaccine)
56 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.
Robert L. Murphy

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.
National Institute of Allergy and Infectious Diseases (NIAID)
Merck Sharp & Dohme LLC
Pfizer
Objectif Recherche Vaccins SIDA

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Robert Murphy, MD, Northwestern University

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.
November 1, 2009

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.
July 1, 2013

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.
June 1, 2014

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).
September 9, 2009

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.
September 11, 2009

First Posted (Estimate)

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.
September 14, 2009

Study Record Updates

Last Update Posted (Estimate)

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.
September 12, 2014

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.
September 10, 2014

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.
September 1, 2014

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.
  • EraMune02

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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