HIV InfectionsPhase 1NCT00703586
Study of the Antiviral and Immunological Effects of Intensification of Suppressive Antiretroviral Therapy With Maraviroc
A Phase 1 study testing Maraviroc in people with HIV Infections, run by Rockefeller University at 1 site in United States.
Trial summary
Hypothesis: Intensification of current ARV regimens with maraviroc will result in more complete suppression of viral replication, particularly in the gastrointestinal mucosa with resultant reduction in markers of immune activation and improved GI immune reconstitution. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- Maraviroc
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2007to May 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Documented treatment with combination antiviral therapy (ARV) during acute and early HIV-1 infection defined as:
- Negative ELISA/Western Blot or indeterminate Western Blot in the presence of HIV-1 RNA>5,000 copies/ml
- Positive HIV-1 serology with a detuned ELISA O.D. value below 1.0
- A documented negative serology within 180 days of screening and a positive HIV-1 serology at screening
- Treatment for at least one year with ARVs
- Plasma HIV-1 RNA levels below detection for at least 6 months
Show all 27Show fewer
- CCR5 tropic virus pretreatment using the Monogram assay
- GI biopsy at study entry
- Agree to subsequent GI biopsy at 12 and 24 weeks
- Laboratory values obtained within 45 days prior to study entry.
- Absolute neutrophil count (ANC) ≥500/mm³
- Hemoglobin ≥9.0 g/dL
- Platelet count ≥80,000/mm³
- AST (SGOT), ALT (SGPT), and alkaline phosphatase < 5.0 x ULN
- Total bilirubin ≤ 2.5 X ULN if not on atazanavir containing regimen
- PT/PTT within 1.5 control
- Calculated creatinine clearance ≥60 mL/min as estimated by the Cockcroft Gault equation:
- For men, (140 - age in years) x (body weight in kg) / (serum creatinine in mg/dL x 72) = CrCl (mL/min)
- For women, multiply the result by 0.85 = CrCl (mL/min) NOTE: A program to assist in calculations is available on the DMC web site at: http://www.fstrf.org/ACTG/ccc.html
- For women of reproductive potential, negative serum or urine pregnancy test within 48 hours prior to initiating study medications unless otherwise specified by product labeling.
- Female candidates of reproductive potential is defined as girls who have reached menarche or women who have not been post-menopausal for at least 24 consecutive months (i.e., who have had menses within the preceding 24 months) or have not undergone surgical sterilization (e.g., hysterectomy, or bilateral oophorectomy, or bilateral tubal ligation).
- Contraception requirements:
- Female candidates of reproductive potential, who are participating in sexual activity that could lead to pregnancy, must agree that they will use at least one reliable method of contraception while receiving the protocol-specified drugs and for 6 weeks after stopping the medications.
- Male Candidates: If you are a heterosexual male, you and your sexual partner must agree to use acceptable methods of birth control during the entire study. Acceptable methods of birth control include intrauterine device (IUD), diaphragm with spermicide,condoms or not having sex. Oral contraceptives alone are not an acceptable method of birth control.
- Men and women age ≥18 years.
- Participants must be HLA-B5701 negative if not taking abacavir as part of their regimen.
- Ability and willingness of subject to give written informed consent.
Who cannot join
- Currently breast-feeding.
- Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry. NOTE: Subjects receiving stable physiologic glucocorticoid doses, defined as prednisone ≤ 10 mg/day, will not be excluded.
- Known allergy/sensitivity to study drugs or their formulations.
- Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
- Serious illness requiring systemic treatment and/or hospitalization until candidate either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 7 days prior to study entry.
- Pretreatment viral population that is either dual mixed tropic or X4 tropic using the Monogram assay
- Current imprisonment or involuntary incarceration in a medical facility for psychiatric or physical (e.g., infectious disease) illness.
- Any other clinical conditions or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with the requirements.
Trial locations and contacts
1 site in 1 country.
United States1 site
Rockefeller University Hospital
New York, New York, 10065
About this study
Official title: A Two-Arm, Single Site, Proof of Concept Study of the Antiviral and Immunological Effects of Intensification of Suppressive Antiretroviral Therapy With Maraviroc, a CCR5 Antagonist (ADARC 2007-02)
Hypothesis: Intensification of current ARV regimens with maraviroc will result in more complete suppression of viral replication, particularly in the gastrointestinal mucosa with resultant reduction in markers of immune activation and improved GI immune reconstitution.
Read the detailed description
- DURATION: Subjects will participate for a minimum of 28 weeks.
- SAMPLE SIZE: 18 subjects randomized 2:1 continued ARVs plus maraviroc versus continued ARVs plus additional ARV to be determined based on baseline ARV regimen.
- REGIMEN: At entry, subjects will be randomized to one of the following in a 2:1 ratio:
ARM A:
Intensification with maraviroc for 24 weeks at one of the following doses:
- 150 mg orally BID when coadministered with a ritonavir-boosted protease inhibitor
- 600 mg orally BID when coadministered with efavirenz or nevirapine
ARM B
Intensification with an additional NRTI for 12 weeks then cross over to maraviroc intensification for an additional 12 weeks as above:
- Addition of abacavir 600 mg orally once daily to a tenofovir containing regimen for 12 weeks then replacing the abacavir with maraviroc
- Addition of an alternate FDA approved NRTI [such as zidovudine (AZT) or didanosine (ddi)] at standard oral dosing to a tenofovir containing regimen for 12 weeks (if the participant declines abacavir therapy) then replacing the alternate NRTI with maraviroc.
The objectives of this study are:
To determine whether intensification of current ARV regimens with maraviroc will result in more complete suppression of viral replication and improved immune reconstitution in GI mucosal lymphoid compartment based on:
- Reduction in normalized levels of CD4+MMC HIV-1 RNA as determined by PCR pre- and post- intensification at week 12 in Arm A versus Arm B.
- Reduction in normalized levels of CD4+ mucosal mononuclear cell (MMC) HIV-1 RNA at week 12 compared to baseline in Arm A.
- Reduction in %CD4+MMC HIV-1 RNA positive as determined by PCR pre- and post- intensification between Arm A and Arm B as well as week 12 and 24 post maraviroc intensification.
- Levels of CD4+ T cells in GALT (% by flow and absolute #s by immunohistochemistry).
- Phenotype of cells in GALT by flow (memory, naive, R5, X4, dual expressing).
- Levels of activation of CD4 and CD8 in PB and GALT using HLA DR and CD 38.
- Conditions
- HIV Infections
- Being tested
- Maraviroc
- Keywords
- Maraviroc, Treatment Experienced
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MaravirocDrug
ARM A:
Addition of maraviroc to baseline ARV medications for 24 weeks at one of the following doses:
- 150 mg orally BID when coadministered with a ritonavir-boosted protease inhibitor
- 600 mg orally BID when coadministered with efavirenz or nevirapine
ARM B:
Addition of an additional NRTI to baseline ARV medications for 12 weeks then cross over to maraviroc intensification for an additional 12 weeks as above:
- Addition of abacavir 600 mg orally once daily to a tenofovir containing regimen for 12 weeks then replacing the abacavir with maraviroc.
- Addition of an alternate FDA approved NRTI [such as zidovudine (AZT) or didanosine (ddi)] at standard oral dosing to a tenofir containing regimen for 12 weeks (if the participant declines abacavir therapy) then replacing the alternate NRTI with maraviroc.
- Addition of tenofovir 300 mg daily to an abacavir containing regimen for 12 weeks then replacing the tenofovir with maraviroc.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | ARM A:
Intensification with maraviroc for 24 weeks at one of the following doses:
* 150 mg orally BID when coadministered with a ritonavir-boosted protease inhibitor
* 600 mg orally BID when coadministered with efavirenz or nevirapine Receives: Drug: Maraviroc |
| 2 | Active comparator | ARM B
Intensification with an additional NRTI for 12 weeks then cross over to maraviroc intensification for an additional 12 weeks as above:
* Addition of abacavir 600 mg orally once daily to a tenofovir containing regimen for 12 weeks then replacing the abacavir with maraviroc
* Addition of an alternate FDA approved NRTI [such as zidovudine (AZT) or didanosine (ddi)] at standard oral dosing to a tenofovir containing regimen for 12 weeks (if the participant declines abacavir therapy) then replacing the alternate NRTI with maraviroc. Receives: Drug: Maraviroc |
What is being measured
The primary outcome is the main question the study is designed to answer.
MMC HIV RNA
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2008 (estimated)
- Study startSep 2007
- Primary completionMay 2011
- Study completionMay 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rockefeller University
- Sponsor type
- University, hospital or other
- Collaborators
- Aaron Diamond AIDS Research Center, Pfizer
- Responsible party
- Sponsor
- Investigators
- Martin Markowitz, MD, Principal investigator, Rockefeller University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00703586
- Sponsor's protocol ID
- MMA-0612
- Status last verified
- Oct 2012
- First submitted
- 19 Jun 2008
- Last updated
- 23 Oct 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Two-Arm, Single Site, Proof of Concept Study of the Antiviral and Immunological Effects of Intensification of Suppressive Antiretroviral Therapy With Maraviroc, a CCR5 Antagonist (ADARC 2007-02)
- ClinicalTrials.gov ID
- NCT00703586
- Acronym / sponsor ID
- MMA-0612
- Conditions
- HIV Infections
- Keywords
- Maraviroc, Treatment Experienced
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Rockefeller UniversityUniversity, hospital or other
- Collaborators
- Aaron Diamond AIDS Research Center, Pfizer
- Study start
- Sep 2007
- Primary completion
- May 2011 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 23 Jun 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hypothesis: Intensification of current ARV regimens with maraviroc will result in more complete suppression of viral replication, particularly in the gastrointestinal mucosa with resultant reduction in markers of immune activation and improved GI immune reconstitution.
Detailed description
- DURATION: Subjects will participate for a minimum of 28 weeks.
- SAMPLE SIZE: 18 subjects randomized 2:1 continued ARVs plus maraviroc versus continued ARVs plus additional ARV to be determined based on baseline ARV regimen.
- REGIMEN: At entry, subjects will be randomized to one of the following in a 2:1 ratio:
ARM A:
Intensification with maraviroc for 24 weeks at one of the following doses:
- 150 mg orally BID when coadministered with a ritonavir-boosted protease inhibitor
- 600 mg orally BID when coadministered with efavirenz or nevirapine
ARM B
Intensification with an additional NRTI for 12 weeks then cross over to maraviroc intensification for an additional 12 weeks as above:
- Addition of abacavir 600 mg orally once daily to a tenofovir containing regimen for 12 weeks then replacing the abacavir with maraviroc
- Addition of an alternate FDA approved NRTI [such as zidovudine (AZT) or didanosine (ddi)] at standard oral dosing to a tenofovir containing regimen for 12 weeks (if the participant declines abacavir therapy) then replacing the alternate NRTI with maraviroc.
The objectives of this study are:
To determine whether intensification of current ARV regimens with maraviroc will result in more complete suppression of viral replication and improved immune reconstitution in GI mucosal lymphoid compartment based on:
- Reduction in normalized levels of CD4+MMC HIV-1 RNA as determined by PCR pre- and post- intensification at week 12 in Arm A versus Arm B.
- Reduction in normalized levels of CD4+ mucosal mononuclear cell (MMC) HIV-1 RNA at week 12 compared to baseline in Arm A.
- Reduction in %CD4+MMC HIV-1 RNA positive as determined by PCR pre- and post- intensification between Arm A and Arm B as well as week 12 and 24 post maraviroc intensification.
- Levels of CD4+ T cells in GALT (% by flow and absolute #s by immunohistochemistry).
- Phenotype of cells in GALT by flow (memory, naive, R5, X4, dual expressing).
- Levels of activation of CD4 and CD8 in PB and GALT using HLA DR and CD 38.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: MaravirocARM A: Intensification with maraviroc for 24 weeks at one of the following doses: * 150 mg orally BID when coadministered with a ritonavir-boosted protease inhibitor * 600 mg orally BID when coadministered with efavirenz or nevirapine |
| 2 | Active comparator | Drug: MaravirocARM B Intensification with an additional NRTI for 12 weeks then cross over to maraviroc intensification for an additional 12 weeks as above: * Addition of abacavir 600 mg orally once daily to a tenofovir containing regimen for 12 weeks then replacing the abacavir with maraviroc * Addition of an alternate FDA approved NRTI [such as zidovudine (AZT) or didanosine (ddi)] at standard oral dosing to a tenofovir containing regimen for 12 weeks (if the participant declines abacavir therapy) then replacing the alternate NRTI with maraviroc. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- Documented treatment with combination antiviral therapy (ARV) during acute and early HIV-1 infection defined as:
- Treatment for at least one year with ARVs
- Plasma HIV-1 RNA levels below detection for at least 6 months
- CCR5 tropic virus pretreatment using the Monogram assay
- GI biopsy at study entry
Key exclusion criteria (8 listed)
- Currently breast-feeding.
- Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry. NOTE: Subjects receiving stable physiologic glucocorticoid doses, defined as prednisone ≤ 10 mg/day, will not be excluded.
- Known allergy/sensitivity to study drugs or their formulations.
- Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
- Serious illness requiring systemic treatment and/or hospitalization until candidate either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 7 days prior to study entry.
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 |
|---|---|---|
| MaravirocARM A: Addition of maraviroc to baseline ARV medications for 24 weeks at one of the following doses: * 150 mg orally BID when coadministered with a ritonavir-boosted protease inhibitor * 600 mg orally BID when coadministered with efavirenz or nevirapine ARM B: Addition of an additional NRTI to baseline ARV medications for 12 weeks then cross over to maraviroc intensification for an additional 12 weeks as above: * Addition of abacavir 600 mg orally once daily to a tenofovir containing regimen for 12 weeks then replacing the abacavir with maraviroc. * Addition of an alternate FDA approved NRTI [such as zidovudine (AZT) or didanosine (ddi)] at standard oral dosing to a tenofir containing regimen for 12 weeks (if the participant declines abacavir therapy) then replacing the alternate NRTI with maraviroc. * Addition of tenofovir 300 mg daily to an abacavir containing regimen for 12 weeks then replacing the tenofovir with maraviroc. | Drug | 1, 2 |
Primary outcome
MMC HIV RNA
Time frame: 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2012.
Related trials for HIV Infections
Not yet recruiting
HealthMpowerment Korea: Pilot Testing the Cultural Adaptation of a Digital HIV Intervention for Men Who Have Sex With Men in South Korea
HIV Infections, HIV Prevention and Care
Not yet recruiting
Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Recruiting
Evaluating the Impact of Using the B-OK Bottles for HIV and ART Literacy in South Africa
HIV, HIV Treatment
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder
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.
Martin Markowitz, MD principal investigator
Rockefeller University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Maraviroc in people with HIV Infections, run by Rockefeller University at 1 site 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 27 inclusion and 8 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 23 Oct 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
MMC HIV RNA (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Oct 2012.