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

NCT00735072

Last updated date
Study Location
University of California San Francisco - San Francisco General Hospital
San Francisco, California, 94110, United States
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
HIV Infection
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

1. 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.

2. Stable antiretroviral therapy for at least 12 months

3. Screening CD4+ T cell count below 350 cells/mm3

4. All available CD4+ T cell counts in the last year and at screening < 350 cells/mm3

5. Screening plasma HIV RNA levels below level of detection (< 50 copies RNA/mL using Roche Amplicor or < 75 copies/mL using Bayer bDNA)

6. 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.

7. > 90% adherence to therapy within the preceding 30 days, as determined by self-report.

8. 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.

9. Ability and willingness of subject or legal guardian/representative to provide informed consent

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


1. Increase in CD4 count of > 100 cells/mm3 in past year.


2. Patients who are intending to modify antiretroviral therapy in the next 24 weeks for
any reason.


3. Serious illness requiring hospitalization or parental antibiotics within preceding 3
months.


4. Concurrent treatment with immunomodulatory drugs, or exposure to any immunomodulatory
drug in past 16 weeks.


5. HBVsAg+ or active hepatitis C or hepatitis B which will require treatment in the
subsequent 24 weeks.


6. Prior exposure to CCR5 inhibitors


7. Screening absolute neutrophil count <1,000 cells/mm3, platelet count <50,000
cells/mm3, hemoglobin < 8mg/dL, estimated creatinine clearance <40 mL/minute.


8. Pregnant or breastfeeding women


9. Use of both Tenofovir and Didanosine in current antiretroviral therapy regimen.

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Advanced Information
Descriptive Information
Brief Title  ICMJE Maraviroc as an Immunomodulatory Drug for Antiretroviral-treated HIV Infected Patients Exhibiting Immunologic Failure
Official Title  ICMJE Maraviroc as an Immunomodulatory Drug for Antiretroviral-treated HIV Infected Patients Exhibiting Immunologic Failure
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE HIV Infection
Intervention  ICMJE
  • 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.
    Other Name: Placebo for Maraviroc
  • Drug: 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.
    Other Name: Selzentry
Study Arms  ICMJE
  • Experimental: Maraviroc
    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).
    Intervention: Drug: Maraviroc
  • Placebo Comparator: Placebo
    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).
    Intervention: Drug: Placebo
Publications * 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.

*   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
Actual Enrollment  ICMJE
 (submitted: June 13, 2012)
45
Original Estimated Enrollment  ICMJE
 (submitted: August 13, 2008)
42
Actual Study Completion Date  ICMJE July 2010
Actual Primary Completion Date April 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. 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.
  2. Stable antiretroviral therapy for at least 12 months
  3. Screening CD4+ T cell count below 350 cells/mm3
  4. All available CD4+ T cell counts in the last year and at screening < 350 cells/mm3
  5. Screening plasma HIV RNA levels below level of detection (< 50 copies RNA/mL using Roche Amplicor or < 75 copies/mL using Bayer bDNA)
  6. 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.
  7. > 90% adherence to therapy within the preceding 30 days, as determined by self-report.
  8. 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.
  9. Ability and willingness of subject or legal guardian/representative to provide informed consent

Exclusion Criteria:

  1. Increase in CD4 count of > 100 cells/mm3 in past year.
  2. Patients who are intending to modify antiretroviral therapy in the next 24 weeks for any reason.
  3. Serious illness requiring hospitalization or parental antibiotics within preceding 3 months.
  4. Concurrent treatment with immunomodulatory drugs, or exposure to any immunomodulatory drug in past 16 weeks.
  5. HBVsAg+ or active hepatitis C or hepatitis B which will require treatment in the subsequent 24 weeks.
  6. Prior exposure to CCR5 inhibitors
  7. Screening absolute neutrophil count <1,000 cells/mm3, platelet count <50,000 cells/mm3, hemoglobin < 8mg/dL, estimated creatinine clearance <40 mL/minute.
  8. Pregnant or breastfeeding women
  9. Use of both Tenofovir and Didanosine in current antiretroviral therapy regimen.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
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 NCT00735072
Other Study ID Numbers  ICMJE GA9001DE
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of California, San Francisco
Study Sponsor  ICMJE University of California, San Francisco
Collaborators  ICMJE
  • Pfizer
  • amfAR, The Foundation for AIDS Research
  • Stanford University
  • Case Western Reserve University
  • Rush University
Investigators  ICMJE
Principal Investigator:Peter W Hunt, MDUniversity of California, San Francisco
Principal Investigator:Steven G Deeks, MDUniversity of California, San Francisco
Principal Investigator:Nancy Shulman, MDStanford University
Principal Investigator:Robert Shafer, MDStanford University
Principal Investigator:Michael Lederman, MDCase Western Reserve University
Principal Investigator:Toyin Adeyemi, MDRush University
PRS Account University of California, San Francisco
Verification Date July 2020

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