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

This study has been completed.
Sponsor:
Collaborators:
Objectif Recherche Vaccins SIDA
Pfizer
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Robert L. Murphy, Northwestern University
ClinicalTrials.gov Identifier:
NCT00976404
First received: September 9, 2009
Last updated: September 10, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
HIV Infection
Biological: DNA + HIV-rAd5 vaccine
Drug: ART intensification (raltegravir)
Drug: ART intensification (maraviroc)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multicenter, Randomized, Non-comparative, Controlled Study of Therapeutic Intensification Plus Immunomodulation in HIV-infected Patients With Long-term Viral Suppression

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Change From Baseline in HIV DNA in PBMCs at Week 56 [ Time Frame: 56 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change From Baseline in HIV DNA in Rectal Tissue at Week 56 [ Time Frame: Week 56 ] [ Designated as safety issue: No ]
  • Change From Baseline in CD4+ T Cell Count at Week 56 [ Time Frame: Week 56 ] [ Designated as safety issue: No ]
  • HIV Specific T-cell Response to Env [ Time Frame: 36 weeks ] [ Designated as safety issue: No ]
    HIV-specific immunity: Interferon gamma ELISpot response to Env (clades A) at week 36 (one month after rAd5 boosting)

  • Serious Adverse Events Attributed to Study Treatments [ Time Frame: 56 weeks ] [ Designated as safety issue: Yes ]
    Grade 3 or 4 serious adverse events related to study treatments (raltegravir, maraviroc, or HIV-recombinant Ad5-based vaccine)


Enrollment: 28
Study Start Date: November 2009
Study Completion Date: June 2014
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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:
  • Selzentry
  • Celsentri
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)
Biological: DNA + HIV-rAd5 vaccine
4 mg subcutaneous injection at weeks 8 (DNA prime), 12 (DNA prime), 16 (DNA prime), and 32 (HIV-rAd5)
Drug: ART intensification (raltegravir)
raltegravir 400 mg PO BID for 56 weeks
Other Name: 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:
  • Selzentry
  • Celsentri

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00976404

Locations
United States, California
University of California San Francisco
San Francisco, California, United States, 94110
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, New York
Cornell University
New York, New York, United States, 10011
Sponsors and Collaborators
Robert L. Murphy
Objectif Recherche Vaccins SIDA
Pfizer
Merck Sharp & Dohme Corp.
Investigators
Study Chair: Robert Murphy, MD Northwestern University
  More Information

No publications provided

Responsible Party: Robert L. Murphy, Professor, Northwestern University
ClinicalTrials.gov Identifier: NCT00976404     History of Changes
Other Study ID Numbers: EraMune02
Study First Received: September 9, 2009
Results First Received: September 4, 2014
Last Updated: September 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Northwestern University:
HIV-1 infection
Treatment intensification
Immunomodulation
HIV-rAd5 vaccine

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Infection
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on September 18, 2014