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

NCT00735072 | Completed Phase 4 Results DMC

• 1 other identifier: GA9001DE
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

HIV Infection

Keywords

HIV infection; T cell activation; Antiretroviral Therapy; CCR5; Maraviroc

Outcome Measures

Primary Outcomes (1)

• Week 24 Change in Percentage of CD8+ T Cells That Co-express CD38 and HLA DR (Week 24 %CD38+HLA-DR+ CD8+ T Cells Minus Baseline %CD38+HLA-DR+ CD8+ T Cells)

  Baseline and Week 24

Secondary Outcomes (4)

• Change in CD4+ T Cell Count

  Baseline and Week 24

• Change in Ultra-sensitive Plasma HIV RNA Level (Single Copy/ml Assay)

  Baseline and Week 24

• Change in Brachial Artery Flow-mediated Dilatation (UCSF Site Only)

  Baseline and Week 24

• Change in Gut-associated Lymphoid Tissue HIV RNA Level (UCSF Site Only)

  Baseline and Week 24

Study Arms (2)

Maraviroc

EXPERIMENTAL

Maraviroc (dose based on current medications in regimen: 150mg orally (PO) twice daily (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

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

Interventions

Placebo DRUG

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.

Also known as: Placebo for Maraviroc

Placebo

Maraviroc DRUG

Dose based on current medications in regimen: 150mg orally (PO) twice daily (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.

Also known as: Selzentry

Maraviroc

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Pfizer: collaborator
• amfAR, The Foundation for AIDS Research: collaborator
• Stanford University: collaborator
• Case Western Reserve University: collaborator
• Rush University: collaborator

Study Sites (4)

University of California San Francisco - San Francisco General Hospital

San Francisco, California, 94110, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Rush University - Stroger Hospital of Cook County

Chicago, Illinois, 60612, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Related Publications (1)

• Hunt PW, Shulman NS, Hayes TL, Dahl V, Somsouk M, Funderburg NT, McLaughlin B, Landay AL, Adeyemi O, Gilman LE, Clagett B, Rodriguez B, Martin JN, Schacker TW, Shacklett BL, Palmer S, Lederman MM, Deeks SG. The immunologic effects of maraviroc intensification in treated HIV-infected individuals with incomplete CD4+ T-cell recovery: a randomized trial. Blood. 2013 Jun 6;121(23):4635-46. doi: 10.1182/blood-2012-06-436345. Epub 2013 Apr 15.

  PMID: 23589670 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Maraviroc

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Peter W. Hunt, MD
• Organization: University of California, San Francisco

phunt@php.ucsf.edu

(415) 476-4082

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2008
• First Posted: August 14, 2008
• Study Start: September 1, 2008
• Primary Completion: April 1, 2010
• Study Completion: July 1, 2010
• Last Updated: August 17, 2020
• Results First Posted: July 18, 2012

Record last verified: 2020-07

Locations

US (4)