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

Sponsor:	Robert L. Murphy
Collaborators:	Objectif Recherche Vaccins SIDA National Institute of Allergy and Infectious Diseases (NIAID) Pfizer Merck
Information provided by (Responsible Party):	Robert L. Murphy, Northwestern University
ClinicalTrials.gov Identifier:	NCT00976404

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 Infections Treatment Experienced	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:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Deoxyribonucleic acid Maraviroc Raltegravir Raltegravir potassium

U.S. FDA Resources

Further study details as provided by Northwestern University:

Primary Outcome Measures:

HIV proviral DNA [ Time Frame: 56 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

HIV DNA in gut lymphoid tissue [ Time Frame: 56 weeks ] [ Designated as safety issue: No ]
HIV plasma viral load (RNA) [ Time Frame: 56 weeks ] [ Designated as safety issue: No ]
CD4+ T cell count [ Time Frame: 56 weeks ] [ Designated as safety issue: No ]
HIV-specific immunity [ Time Frame: 56 weeks ] [ Designated as safety issue: No ]
T cell activation (CD38) [ Time Frame: 56 weeks ] [ Designated as safety issue: No ]
Adenovirus-specific immunity [ Time Frame: 56 weeks ] [ Designated as safety issue: No ]
Adverse events attributed to study treatments (raltegravir, maraviroc, or HIV-recombinant Ad5-based vaccine) [ Time Frame: 56 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	28
Study Start Date:	November 2009
Estimated Study Completion Date:	December 2012
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: ART intensification only Maintenance of suppressive ART with the addition of raltegravir and maraviroc.	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: ART intensification plus immunomodulation Maintenance of suppressive ART with the addition of raltegravir and maraviroc PLUS immunomodulation therapy with HIV-recombinant Ad5-based vaccine (added after 8 weeks of ART intensification)	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

Arms

Assigned Interventions

Active Comparator: ART intensification only

Maintenance of suppressive ART with the addition of raltegravir and maraviroc.

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: ART intensification plus immunomodulation

Maintenance of suppressive ART with the addition of raltegravir and maraviroc PLUS immunomodulation therapy with HIV-recombinant Ad5-based vaccine (added after 8 weeks of ART intensification)

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

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

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

National Institute of Allergy and Infectious Diseases (NIAID)

Pfizer

Merck

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
Last Updated:	January 26, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Northwestern University:

HIV-1 infection

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
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 May 23, 2012