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

This study has been completed.

Sponsor:

Collaborators:

Objectif Recherche Vaccins SIDA

National Institute of Allergy and Infectious Diseases (NIAID)

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

History of Changes

Tracking Information

First Received Date ^ICMJE

September 9, 2009

Last Updated Date

September 10, 2014

Start Date ^ICMJE

November 2009

Primary Completion Date

July 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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

Original Primary Outcome Measures ^ICMJE

HIV proviral DNA [ Time Frame: 56 weeks ]

Change History

Complete list of historical versions of study NCT00976404 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

Change From Baseline in HIV DNA in Rectal Tissue at Week 56 [ Time Frame: Week 56 ]
Change From Baseline in CD4+ T Cell Count at Week 56 [ Time Frame: 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)
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)

Original Secondary Outcome Measures ^ICMJE

HIV DNA in gut lymphoid tissue [ Time Frame: 56 weeks ]
HIV plasma viral load (RNA) [ Time Frame: 56 weeks ]
CD4+ T cell count [ Time Frame: 56 weeks ]
HIV-specific immunity [ Time Frame: 56 weeks ]
T cell activation (CD38) [ Time Frame: 56 weeks ]
Adenovirus-specific immunity [ Time Frame: 56 weeks ]
Adverse events attributed to study treatments (raltegravir, maraviroc, or HIV-recombinant Ad5-based vaccine) [ Time Frame: 56 weeks ]

Current Other Outcome Measures ^ICMJE

Not Provided

Original Other Outcome Measures ^ICMJE

Not Provided

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

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

Brief Summary

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.

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 ^ICMJE

Interventional

Study Phase

Phase 2

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Condition ^ICMJE

HIV Infection

Intervention ^ICMJE

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

Study Arms

Active Comparator: Maraviroc + raltegravir intensification
ART Intensification (addition of raltegravir and maraviroc to suppressive ART for 56 weeks)
Interventions:
- Drug: ART intensification (raltegravir)
- Drug: ART intensification (maraviroc)
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)
Interventions:
- Biological: DNA + HIV-rAd5 vaccine
- Drug: ART intensification (raltegravir)
- Drug: ART intensification (maraviroc)

Publications *

Achenbach CJ, Assoumou L, Deeks SG, Wilkin TJ, Berzins B, Casazza JP, Lambert-Niclot S, Koup RA, Costagliola D, Calvez V, Katlama C, Autran B, Murphy RL; EraMune 02 study team. Effect of therapeutic intensification followed by HIV DNA prime and rAd5 boost vaccination on HIV-specific immunity and HIV reservoir (EraMune 02): a multicentre randomised clinical trial. Lancet HIV. 2015 Mar;2(3):e82-91. doi: 10.1016/S2352-3018(15)00026-0. Epub 2015 Feb 17.

* 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

Enrollment ^ICMJE

Completion Date

June 2014

Primary Completion Date

July 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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

Sex/Gender

Sexes Eligible for Study:

All

Ages

18 Years to 70 Years (Adult, Senior)

Accepts Healthy Volunteers

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Listed Location Countries ^ICMJE

United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT00976404

Other Study ID Numbers ^ICMJE

EraMune02

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

Not Provided

Plan to Share Data

Not Provided

IPD Description

Not Provided

Responsible Party

Robert L. Murphy, Northwestern University

Study Sponsor ^ICMJE

Robert L. Murphy

Collaborators ^ICMJE

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

Investigators ^ICMJE

Study Chair:

Robert Murphy, MD

Northwestern University

PRS Account

Northwestern University

Verification Date

September 2014

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

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