HIVPhase 1MVC-PREPNCT01749566
Exploring HIV Entry Blockade as a Pre-exposure Prophylaxis Strategy in Women
A Phase 1 study testing maraviroc in people with HIV, run by Emory University at 1 site in United States.
Trial summary
Pre-exposure prophylaxis (PrEP) is an HIV prevention strategy in which HIV medicines are used by a person before they are exposed to HIV in order to decrease his or her chance of getting infected. Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- HIV
- What is being tested?
- maraviroc
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2012to May 2015
- 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
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Female sex, defined by sex at birth
- Age greater than or equal to 18 years
- Negative HIV serology at screening
- Normal menses (within 22-35 day intervals) for at least 3 cycles
- Intact uterus and cervix
- Normal chemistry and CBC panels at screening, including
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- Absolute neutrophil count (ANC) greater than 750/mm3
- Hemoglobin greater than 10.0 g/dL
- Platelet count greater than 100,000/mm3
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase less than 3 x upper limit of normal
- Total bilirubin less than 2.5 x upper limit of normal
- CrCl greater than or equal to 60 mL/min as estimated by the Cockcroft- Gault equation
- Negative hepatitis B surface antigen
- Willing to use condoms for the duration of the study and abstain from sexual intercourse for 48 hours before each genital tract sampling
- Able and willing to provide informed consent
Who cannot join
- Pregnancy (by clinical history or positive urine pregnancy test at screening)
- Breastfeeding
- Alcohol or substance use that, in the opinion of the study investigator, would interfere with the conduct of the study
- History of loop electrosurgical excision procedure (LEEP), conization, or cryosurgery
- Use of systemic hormonal contraception
- Orthostasis at screening, defined as systolic blood pressure decrease of at least 20 mm Hg or a diastolic blood pressure decrease of at least 10 mm Hg within three minutes of standing.
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- Known history of heart or liver disease
- Known history of any medical condition that would interfere with conduct of the study, in the opinion of the study investigator
- Symptoms of active vaginal infection at the time of screening, including new ulcerative genital lesions or purulent and/or foul-smelling vaginal discharge
- Visible ulcerative genital lesions or purulent vaginal discharge during speculum pelvic examination performed at the time of screening
- Concomitant use of medications that interact with maraviroc or known allergy to maraviroc
Trial locations and contacts
1 site in 1 country.
United States1 site
Grady Infectious Diseases Program
Atlanta, Georgia, 30303
About this study
Pre-exposure prophylaxis (PrEP) is an HIV prevention strategy in which HIV medicines are used by a person before they are exposed to HIV in order to decrease his or her chance of getting infected. In this study, we will investigate a new PrEP strategy in women using a drug called maraviroc, a medicine used in the treatment of HIV infection called a CCR5 antagonist. We hypothesize that maraviroc could be a particularly good drug for PrEP because it achieves high concentrations in the genital tract in women and decreases the number of HIV-susceptible cells in the genital tract, and thus could potentially be dosed in more favorable ways than the current PrEP drugs.
In order to further evaluate this PrEP strategy, we plan to measure the amount of maraviroc in the blood and genital tract of HIV-negative healthy female volunteers before, during, and after they are given maraviroc dosed either in the standard (twice a day) or reduced (once a day) dose for 7 days compared with women who are not given maraviroc. We will also study immune cells from the blood and genital tract from these women to see if maravoric has an effect on these cells that would prevent them from becoming infected with HIV.
Read the detailed description
RATIONALE Globally, over half of HIV-infected adults are women, and in the United States, 25% of all HIV/AIDS cases occur in women. Women often lack control over many available prevention measures, underscoring a critical need to enhance HIV prevention options for women. Pre-exposure prophylaxis (PrEP) is an HIV prevention strategy in which antiretroviral (ARV) drugs are used prior to potential HIV exposure to reduce the likelihood of infection. This strategy, which usually contains the drug tenofovir disoproxil fumarate (TDF), has recently shown promise, but efficacy data suggest room for improvement, particularly for women, in whom these data are conflicting. This study aims to prospectively examine ARV pharmacology and mucosal immunology in order to evaluate a novel PrEP strategy in women - blockade of HIV entry from its target cells at the mucosal surface using the CCR5 receptor antagonist maraviroc (MVC). These actions of CCR5 receptor antagonism, if validated, could lead to reduced HIV acquisition risk at more favorable dosing strategies than available for current PrEP. Knowledge of pharmacological modulation of mucosal immunity and HIV acquisition risk is fundamental to understanding, improving, and designing new PrEP strategies.
DESIGN This is a prospective, observational cohort study with an intensive pharmacokinetic component conducted in HIV-negative healthy women. Genital tract and whole blood samples will be collected before, during, and after treatment with 7 days of oral MVC, dosed at 300mg twice daily (standard) or 300mg daily (reduced) compared with no treatment (control). Genital tract and plasma MVC concentration will be measured using intensive pharmacokinetic sampling to generate concentration-time profiles. Peripheral blood mononuclear cells (PBMC) and endocervical cells harvested from whole blood and cervicovaginal lavage respectively will be analyzed for CCR5 receptor occupancy, the number of CCR5-expressing HIV target cells, and level of T cell activation.
DURATION 21 days after the first visit of the last participants. Enrollment is expected to take 12 months.
SAMPLE SIZE 30 subjects (10 subjects per study group)
POPULATION HIV-negative healthy women, age 18 years or older, with normal menses.
- Conditions
- HIV
- Being tested
- maraviroc
- Keywords
- HIV/AIDS, preexposure prophylaxis, women's health
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
maravirocDrug
Also called Selzentry
Maraviroc administered at standard (300mg po bid) or reduced (300mg po daily) dosing
| Study group | Role | What they receive |
|---|---|---|
| Group A (standard maraviroc dosing) | Active comparator | maraviroc 300mg po bid x 7 days Receives: Drug: maraviroc |
| Group B (reduced maraviroc dosing) | Active comparator | maraviroc 300mg po daily x 7 days Receives: Drug: maraviroc |
| Group C (no drug) | No intervention | No additional drug |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in female genital tract maraviroc concentration
Measured: Day 0, 7, 10-12
Secondary outcomes (3)
Female genital tract HIV target cells
HIV target cell availability (CCR5+ CD4+ T lymphocytes) in the FGT compared with blood
Measured: Day 0, 7, 10-12, 14, 21
Female genital tract T cell activation
T cell activation (HLA-DR+ CD38+ CD4+ T-lymphocytes) in the FGT compared with blood
Measured: Day 0, 7, 10-12, 14, 21
Vaginal microbiome
Determine the effect of CCR5 receptor blockade on the vaginal microbiome in healthy women
Measured: Day 0, 7, 10-12, 14, 21
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2012 (estimated)
- Study startDec 2012
- Primary completionMay 2015
- Study completionMay 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe 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 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Anandi Sheth, Emory University
- Investigators
- Anandi Sheth, MD, Principal investigator, Emory University School of Medicine, Department of Medicine, Division of Infectious Diseases
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01749566
- Sponsor's protocol ID
- IRB00059752
- Other IDs
- KL2TR000455, ACTSIKL22012
- Acronym
- MVC-PREP
- Status last verified
- Jul 2015
- First submitted
- 9 Nov 2012
- Last updated
- 9 Jul 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploring HIV Entry Blockade as a Pre-exposure Prophylaxis Strategy in Women
- ClinicalTrials.gov ID
- NCT01749566
- Acronym / sponsor ID
- MVC-PREP / IRB00059752
- Conditions
- HIV
- Keywords
- HIV/AIDS, preexposure prophylaxis, women's health
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Study start
- Dec 2012
- Primary completion
- May 2015 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 13 Dec 2012 (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.
Pre-exposure prophylaxis (PrEP) is an HIV prevention strategy in which HIV medicines are used by a person before they are exposed to HIV in order to decrease his or her chance of getting infected. In this study, we will investigate a new PrEP strategy in women using a drug called maraviroc, a medicine used in the treatment of HIV infection called a CCR5 antagonist. We hypothesize that maraviroc could be a particularly good drug for PrEP because it achieves high concentrations in the genital tract in women and decreases the number of HIV-susceptible cells in the genital tract, and thus could potentially be dosed in more favorable ways than the current PrEP drugs.
In order to further evaluate this PrEP strategy, we plan to measure the amount of maraviroc in the blood and genital tract of HIV-negative healthy female volunteers before, during, and after they are given maraviroc dosed either in the standard (twice a day) or reduced (once a day) dose for 7 days compared with women who are not given maraviroc. We will also study immune cells from the blood and genital tract from these women to see if maravoric has an effect on these cells that would prevent them from becoming infected with HIV.
Detailed description
RATIONALE Globally, over half of HIV-infected adults are women, and in the United States, 25% of all HIV/AIDS cases occur in women. Women often lack control over many available prevention measures, underscoring a critical need to enhance HIV prevention options for women. Pre-exposure prophylaxis (PrEP) is an HIV prevention strategy in which antiretroviral (ARV) drugs are used prior to potential HIV exposure to reduce the likelihood of infection. This strategy, which usually contains the drug tenofovir disoproxil fumarate (TDF), has recently shown promise, but efficacy data suggest room for improvement, particularly for women, in whom these data are conflicting. This study aims to prospectively examine ARV pharmacology and mucosal immunology in order to evaluate a novel PrEP strategy in women - blockade of HIV entry from its target cells at the mucosal surface using the CCR5 receptor antagonist maraviroc (MVC). These actions of CCR5 receptor antagonism, if validated, could lead to reduced HIV acquisition risk at more favorable dosing strategies than available for current PrEP. Knowledge of pharmacological modulation of mucosal immunity and HIV acquisition risk is fundamental to understanding, improving, and designing new PrEP strategies.
DESIGN This is a prospective, observational cohort study with an intensive pharmacokinetic component conducted in HIV-negative healthy women. Genital tract and whole blood samples will be collected before, during, and after treatment with 7 days of oral MVC, dosed at 300mg twice daily (standard) or 300mg daily (reduced) compared with no treatment (control). Genital tract and plasma MVC concentration will be measured using intensive pharmacokinetic sampling to generate concentration-time profiles. Peripheral blood mononuclear cells (PBMC) and endocervical cells harvested from whole blood and cervicovaginal lavage respectively will be analyzed for CCR5 receptor occupancy, the number of CCR5-expressing HIV target cells, and level of T cell activation.
DURATION 21 days after the first visit of the last participants. Enrollment is expected to take 12 months.
SAMPLE SIZE 30 subjects (10 subjects per study group)
POPULATION HIV-negative healthy women, age 18 years or older, with normal menses.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group A (standard maraviroc dosing) | Active comparator | Drug: maravirocmaraviroc 300mg po bid x 7 days |
| Group B (reduced maraviroc dosing) | Active comparator | Drug: maravirocmaraviroc 300mg po daily x 7 days |
| Group C (no drug) | No intervention | –No additional drug |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Female sex, defined by sex at birth
- Age greater than or equal to 18 years
- Negative HIV serology at screening
- Normal menses (within 22-35 day intervals) for at least 3 cycles
- Intact uterus and cervix
Key exclusion criteria (11 listed)
- Pregnancy (by clinical history or positive urine pregnancy test at screening)
- Breastfeeding
- Alcohol or substance use that, in the opinion of the study investigator, would interfere with the conduct of the study
- History of loop electrosurgical excision procedure (LEEP), conization, or cryosurgery
- Use of systemic hormonal contraception
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 |
|---|---|---|
| maravirocAlso: SelzentryMaraviroc administered at standard (300mg po bid) or reduced (300mg po daily) dosing | Drug | Group A (standard maraviroc dosing), Group B (reduced maraviroc dosing) |
Primary outcome
Change in female genital tract maraviroc concentration
Time frame: Day 0, 7, 10-12
3 secondary outcomes
Female genital tract HIV target cells
Time frame: Day 0, 7, 10-12, 14, 21
Female genital tract T cell activation
Time frame: Day 0, 7, 10-12, 14, 21
Vaginal microbiome
Time frame: Day 0, 7, 10-12, 14, 21
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 9 Jul 2015.
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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.
Anandi Sheth, MD principal investigator
Emory University School of Medicine, Department of Medicine, Division of Infectious Diseases
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, run by Emory 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 15 inclusion and 11 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 9 Jul 2015. 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?
Change in female genital tract maraviroc concentration (time frame: Day 0, 7, 10-12). 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 9 Jul 2015.