HIV InfectionPhase 4NCT00735072
Maraviroc as an Immunomodulatory Drug for Antiretroviral-treated HIV Infected Patients Exhibiting Immunologic Failure
A Phase 4 study testing Maraviroc in people with HIV Infection, run by University of California, San Francisco at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infection
- What is being tested?
- Maraviroc
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 4 sitesUnited States
- Study dates
- Sep 2008to Jul 2010
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- > 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Rush University - Stroger Hospital of Cook County
Chicago, Illinois, 60612
Case Western Reserve University
Cleveland, Ohio, 44106
University of California San Francisco - San Francisco General Hospital
San Francisco, California, 94110
Stanford University
Stanford, California, 94305
About this study
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.
Read the 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.
- Conditions
- HIV Infection
- Being tested
- Placebo, Maraviroc
- Keywords
- HIV infection, T cell activation, Antiretroviral Therapy, CCR5, Maraviroc
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Also called Placebo for 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.
MaravirocDrug
Also called Selzentry
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.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Baseline and Week 24
Secondary outcomes (4)
Change in CD4+ T Cell Count
Measured: Baseline and Week 24
Change in Ultra-sensitive Plasma HIV RNA Level (Single Copy/ml Assay)
Measured: Baseline and Week 24
Change in Brachial Artery Flow-mediated Dilatation (UCSF Site Only)
Measured: Baseline and Week 24
Change in Gut-associated Lymphoid Tissue HIV RNA Level (UCSF Site Only)
Measured: Baseline and Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2008 (estimated)
- Study startSep 2008
- Primary completionApr 2010
- Study completionJul 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer, amfAR, The Foundation for AIDS Research, Stanford University, Case Western Reserve University, Rush University
- Responsible party
- Sponsor
- Investigators
- Peter W Hunt, MD, Principal investigator, University of California, San FranciscoSteven G Deeks, MD, Principal investigator, University of California, San FranciscoNancy Shulman, MD, Principal investigator, Stanford UniversityRobert Shafer, MD, Principal investigator, Stanford UniversityMichael Lederman, MD, Principal investigator, Case Western Reserve UniversityToyin Adeyemi, MD, Principal investigator, Rush University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00735072
- Sponsor's protocol ID
- GA9001DE
- Status last verified
- Jul 2020
- First submitted
- 12 Aug 2008
- Last updated
- 17 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 23589670
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Maraviroc as an Immunomodulatory Drug for Antiretroviral-treated HIV Infected Patients Exhibiting Immunologic Failure
- ClinicalTrials.gov ID
- NCT00735072
- Acronym / sponsor ID
- GA9001DE
- Conditions
- HIV Infection
- Keywords
- HIV infection, T cell activation, Antiretroviral Therapy, CCR5, Maraviroc
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Pfizer, amfAR, The Foundation for AIDS Research, Stanford University, Case Western Reserve University, Rush University
- Study start
- Sep 2008
- Primary completion
- Apr 2010 (actual)
- Study completion
- Jul 2010 (actual)
- First posted
- 14 Aug 2008 (estimated)
- Results
- Posted 18 Jul 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Maraviroc | Experimental | Drug: MaravirocMaraviroc (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 | Placebo comparator | Drug: PlaceboPlacebo (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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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)
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboAlso: Placebo for MaravirocDose 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 |
| MaravirocAlso: SelzentryDose 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 |
Primary outcome
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
4 secondary outcomes
Change in CD4+ T Cell Count
Time frame: Baseline and Week 24
Change in Ultra-sensitive Plasma HIV RNA Level (Single Copy/ml Assay)
Time frame: Baseline and Week 24
Change in Brachial Artery Flow-mediated Dilatation (UCSF Site Only)
Time frame: Baseline and Week 24
Change in Gut-associated Lymphoid Tissue HIV RNA Level (UCSF Site Only)
Time frame: Baseline and Week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23589670Hunt 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter W Hunt, MD principal investigator
University of California, San Francisco
Steven G Deeks, MD principal investigator
University of California, San Francisco
Nancy Shulman, MD principal investigator
Stanford University
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Maraviroc in people with HIV Infection, run by University of California, San Francisco at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jul 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00735072, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2020.