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

Primary Purpose

HIV Infection

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Placebo

Maraviroc

About this trial

This is an interventional treatment trial for HIV Infection focused on measuring HIV infection, T cell activation, Antiretroviral Therapy, CCR5, Maraviroc

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University of California San Francisco - San Francisco General Hospital
Stanford University
Rush University - Stroger Hospital of Cook County
Case Western Reserve University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Maraviroc

Placebo

Arm Description

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).

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).

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Change in CD4+ T Cell Count

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

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

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

Full Information

NCT ID

NCT00735072

First Posted

August 12, 2008

Last Updated

July 23, 2020

Sponsor

University of California, San Francisco

Collaborators

Pfizer, amfAR, The Foundation for AIDS Research, Stanford University, Case Western Reserve University, Rush University

1. Study Identification

Unique Protocol Identification Number

NCT00735072

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2020

Overall Recruitment Status

Completed

Study Start Date

September 2008 (undefined)

Primary Completion Date

April 2010 (Actual)

Study Completion Date

July 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of California, San Francisco

Collaborators

Pfizer, amfAR, The Foundation for AIDS Research, Stanford University, Case Western Reserve University, Rush University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV Infection

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

45 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Maraviroc

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

Placebo for Maraviroc

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Maraviroc

Other Intervention Name(s)

Selzentry

Intervention Description

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.

Primary Outcome Measure Information:

Title

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)

Time Frame

Baseline and Week 24

Secondary Outcome Measure Information:

Title

Change in CD4+ T Cell Count

Time Frame

Baseline and Week 24

Title

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

Time Frame

Baseline and Week 24

Title

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

Time Frame

Baseline and Week 24

Title

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

Time Frame

Baseline and Week 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials: