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

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

28

Phase

  • 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

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
Intervention / Treatment
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

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

Secondary Outcome Measures

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

Robert L. Murphy

Collaborators

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

Investigators

  • 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

November 1, 2009

Primary Completion (Actual)

July 1, 2013

Study Completion (Actual)

June 1, 2014

Study Registration Dates

First Submitted

September 9, 2009

First Submitted That Met QC Criteria

September 11, 2009

First Posted (Estimate)

September 14, 2009

Study Record Updates

Last Update Posted (Estimate)

September 12, 2014

Last Update Submitted That Met QC Criteria

September 10, 2014

Last Verified

September 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID 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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