Maraviroc as an Immunomodulatory Drug for Antiretroviral-treated HIV Infected Patients Exhibiting Immunologic Failure - Full Text View

Sponsor:	University of California, San Francisco
Collaborators:	Pfizer American Foundation for AIDS Research Stanford University Case Western Reserve University Rush University
Information provided by:	University of California, San Francisco
ClinicalTrials.gov Identifier:	NCT00735072

Purpose

Many people with HIV fail to regain normal CD4 counts despite effectively suppressing HIV replication with medications. Blocking the "co-receptor" for HIV might decrease inflammation of the immune system, potentially providing an immune benefit. The goal of the current trial is to determine whether adding maraviroc, a new CCR5 "co-receptor" blocker, decreases inflammation, providing an immune benefit for patients with low CD4 counts despite undetectable viral loads on HIV medications.

In this study, HIV-infected patients who are receiving antiretroviral therapy for HIV will receive either maraviroc or a placebo (sugar pill) each day for 24 weeks. After 24 weeks, the study medication will be stopped and all subjects will be followed for 12 more weeks. Blood tests measuring the extent of inflammation, low-level viremia, and immune function will be measured throughout the trial and compared between treatment arms.

Condition	Intervention	Phase
HIV Infection	Drug: Maraviroc Drug: Placebo	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	Maraviroc as an Immunomodulatory Drug for Antiretroviral-treated HIV Infected Patients Exhibiting Immunologic Failure

Resource links provided by NLM:

MedlinePlus related topics: AIDS

Drug Information available for: Maraviroc

U.S. FDA Resources

Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:

Change in % CD38+ HLA-DR+ CD8+ T cells [ Time Frame: Week 24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change in CD4+ T cell count [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
Change in ultra-sensitive plasma HIV RNA level (single copy/ml assay) [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
Change in brachial artery flow-mediated dilatation (UCSF site only) [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
Change in gut-associated lymphoid tissue HIV RNA level (UCSF site only) [ Time Frame: Week 24 ] [ Designated as safety issue: No ]

Estimated Enrollment:	42
Study Start Date:	August 2008
Estimated Study Completion Date:	July 2010
Estimated Primary Completion Date:	April 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Maraviroc: Experimental Maraviroc (dose based on current medications in regimen: 150mg PO BID for those on a protease inhibitor-based regimen other than Tipranavir; 600mg PO BID for efavirenz-containing regimens; or 300 mg PO BID for all other regimens).	Drug: Maraviroc Dose based on current medications in regimen: 150mg PO BID for those on a protease inhibitor-based regimen other than Tipranavir; 600mg PO BID for efavirenz-containing regimens; or 300 mg PO BID for all other regimens.
Placebo: Placebo Comparator Placebo (dose based on current medications in regimen: 150mg PO BID for those on a protease inhibitor-based regimen other than Tipranavir; 600mg PO BID for efavirenz-containing regimens; or 300 mg PO BID for all other regimens).	Drug: Placebo Dose based on current medications in regimen: 150mg PO BID for those on a protease inhibitor-based regimen other than Tipranavir; 600mg PO BID for efavirenz-containing regimens; or 300 mg PO BID for all other regimens.

Detailed Description:

Our primary hypothesis is that CCR5 inhibitors may have protective immunomodulatory effects independent of their impact on HIV replication. Specifically, we predict that maraviroc will reduce the persistent T cell activation that prevents normal immune reconstitution during HAART-mediated viral suppression. This hypothesis will be tested in the context of a placebo controlled pilot study assessing the impact of maraviroc in antiretroviral-treated patients with a CD4+ T cell count less than 350 cells/mm3. In order to address the immunologic activity of this drug independent of plasma HIV RNA levels, we will study individuals who have undetectable viral loads (< 75 copies RNA/mL). Subjects will be randomized to maraviroc for 24 weeks or matching placebo for 24 weeks, followed by a 12 week washout period. We will use as our primary endpoint the proportion of CD8+ T cells that co-expresses CD38 and HLA-DR, as these outcomes have been well validated in prior studies. The primary outcome will be change in the percentage of activated CD8+ T cells at week 24. Change in CD4+ T cell counts, HIV RNA levels (using ultra-sensitive techniques), and other more experimental immunologic measurements will be assessed as secondary outcomes.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

HIV-1 infection, as documented by any licensed ELISA test kit and confirmed by Western blot at any time prior to study entry. HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test.
Stable antiretroviral therapy for at least 12 months
Screening CD4+ T cell count below 350 cells/mm3
All available CD4+ T cell counts in the last year and at screening < 350 cells/mm3
Screening plasma HIV RNA levels below level of detection (< 50 copies RNA/mL using Roche Amplicor or < 75 copies/mL using Bayer bDNA)
All available plasma HIV RNA levels within past year below the level of detection. Isolated values that are detectable but < 500 copies will be allowed as long as the plasma HIV RNA levels before and after this time point are undetectable.
> 90% adherence to therapy within the preceding 30 days, as determined by self-report.
Both male and female subjects are eligible. Females of childbearing potential must have a negative serum pregnancy test at screening and agree to use a double-barrier method of contraception throughout the study period.
Ability and willingness of subject or legal guardian/representative to provide informed consent

Exclusion Criteria:

Increase in CD4 count of > 100 cells/mm3 in past year.
Patients who are intending to modify antiretroviral therapy in the next 24 weeks for any reason.
Serious illness requiring hospitalization or parental antibiotics within preceding 3 months.
Concurrent treatment with immunomodulatory drugs, or exposure to any immunomodulatory drug in past 16 weeks.
HBVsAg+ or active hepatitis C or hepatitis B which will require treatment in the subsequent 24 weeks.
Prior exposure to CCR5 inhibitors
Screening absolute neutrophil count <1,000 cells/mm3, platelet count <50,000 cells/mm3, hemoglobin < 8mg/dL, estimated creatinine clearance <40 mL/minute.
Pregnant or breastfeeding women
Use of both Tenofovir and Didanosine in current antiretroviral therapy regimen.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00735072

Contacts

Contact: Peter W Hunt, MD	(415) 476-4082 ext 345	phunt@php.ucsf.edu
Contact: Steven G Deeks, MD	(415) 476-4082 ext 404	sdeeks@php.ucsf.edu

Locations

United States, California
University of California San Francisco - San Francisco General Hospital	Recruiting
San Francisco, California, United States, 94110
Contact: Peter W Hunt, MD 415-476-4082 ext 345 phunt@php.ucsf.edu
Contact: Steven G. Deeks, MD (415) 476-4082 ext 404 sdeeks@php.ucsf.edu
Principal Investigator: Peter W Hunt, MD
Sub-Investigator: Steven G. Deeks, MD
Stanford University	Recruiting
Stanford, California, United States, 94305
Contact: Debbie Slamowitz, RN 650-723-2804 dslam@stanford.edu
Principal Investigator: Robert Shafer, MD
Sub-Investigator: Nancy Shulman, MD
United States, Illinois
Rush University - Stroger Hospital of Cook County	Recruiting
Chicago, Illinois, United States, 60612
Contact: Toyin Adeyemi 312-864-4573 Oluwatoyin_Adeyemi@rush.edu
Principal Investigator: Toyin Adeyemi, MD
Sub-Investigator: Alan Landay, PhD
United States, Ohio
Case Western Reserve University	Recruiting
Cleveland, Ohio, United States, 44106
Contact: Jane Baum, RN 216-844-2546 baum.jane@clevelandactu.org
Principal Investigator: Michael Lederman, MD

Sponsors and Collaborators

University of California, San Francisco

Pfizer

American Foundation for AIDS Research

Stanford University

Case Western Reserve University

Rush University

Investigators

Principal Investigator:	Peter W Hunt, MD	University of California, San Francisco
Principal Investigator:	Steven G Deeks, MD	University of California, San Francisco
Principal Investigator:	Nancy Shulman, MD	Stanford University
Principal Investigator:	Robert Shafer, MD	Stanford University
Principal Investigator:	Michael Lederman, MD	Case Western Reserve University
Principal Investigator:	Toyin Adeyemi, MD	Rush University

More Information

No publications provided

Responsible Party:	University of California, San Francisco ( Peter W. Hunt, MD )
Study ID Numbers:	GA9001DE
Study First Received:	August 12, 2008
Last Updated:	August 16, 2009
ClinicalTrials.gov Identifier:	NCT00735072 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by University of California, San Francisco:

HIV infection
T cell activation
Antiretroviral Therapy
CCR5
Maraviroc

Additional relevant MeSH terms:

Communicable Diseases
RNA Virus Infections
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Immune System Diseases
Acquired Immunodeficiency Syndrome
Infection

Immunologic Deficiency Syndromes
Virus Diseases
HIV Infections
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections

ClinicalTrials.gov processed this record on November 20, 2009