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Evaluating the Safety and Tolerability of Antiretroviral Drug Regimens Used as Pre-Exposure Prophylaxis to Prevent HIV Infection in At-Risk Men Who Have Sex With Men and in At-Risk Women

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2014 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
Collaborators:
HIV Prevention Trials Network (HPTN)
AIDS Clinical Trials Group (ACTG)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01505114
First received: January 4, 2012
Last updated: November 4, 2014
Last verified: November 2014
  Purpose

Pre-exposure prophylaxis (PrEP) is a method of preventing HIV infection through the use of antiretroviral (ARV) medications before exposure to HIV. This study will evaluate the safety and tolerability of four ARV regimens in preventing HIV infection in men who have sex with men who may be at risk of getting HIV infection through sex and women who may be at risk of getting HIV infection through sex. The four ARV regimens being evaluated are maraviroc (MVC), MVC plus emtricitabine (FTC), MVC plus tenofovir disoproxil fumarate (TDF), and TDF plus FTC. The MVC-containing arms will be compared to TDF/FTC alone and in combination.


Condition Intervention Phase
HIV Infection
Drug: Maraviroc
Drug: Emtricitabine
Drug: Tenofovir disoproxil fumarate
Other: Maraviroc placebo
Other: Emtricitabine placebo
Other: Tenofovir disoproxil fumarate placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: A Phase II Randomized, Double-Blind, Study of the Safety and Tolerability of Maraviroc (MVC), Maraviroc + Emtricitabine (MVC+FTC), Maraviroc + Tenofovir Disoproxil Fumarate (MVC+TDF), or Tenofovir Disoproxil Fumarate + Emtricitabine (TDF+FTC) For Pre-Exposure Prophylaxis (PrEP) To Prevent HIV Transmission in At-Risk Men Who Have Sex With Men and in At-Risk Women

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Occurrence of Grade 3 or higher adverse events (AEs) [ Time Frame: Through Week 48 ] [ Designated as safety issue: Yes ]
  • Tolerability as assessed by time to permanent discontinuation of treatment [ Time Frame: Through Week 48 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Occurrence of Grade 2 or higher AEs that lead to temporary or permanent hold of study drug [ Time Frame: Through Week 48 ] [ Designated as safety issue: Yes ]
  • Changes in creatinine clearance and fractional excretion of phosphate [ Time Frame: Through Week 49 ] [ Designated as safety issue: Yes ]
  • Changes in total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) (calculated or measured), and triglycerides [ Time Frame: From enrollment to Week 48 ] [ Designated as safety issue: No ]
  • Changes in bone mineral density (BMD) [ Time Frame: From enrollment to Week 48 ] [ Designated as safety issue: No ]
  • Changes in peripheral blood and gut-associated lymphoid tissue (GALT) T cell phenotype [ Time Frame: From enrollment to Week 49 ] [ Designated as safety issue: No ]
  • Pre-dose and post-dose concentrations of MVC, FTC, and tenofovir (TFV) in plasma (Drug Interaction Subset) [ Time Frame: At Week 2 ] [ Designated as safety issue: No ]
  • Pre-dose concentrations of drugs (MVC, FTC, TFV, and their phosphorylated derivatives), in plasma, peripheral blood mononuclear cells (PBMCs), and rectal and cervical samples (Tissue Subset) [ Time Frame: At Weeks 24, 48, and 49 ] [ Designated as safety issue: No ]
  • PrEP adherence as assessed by proportion of daily doses taken, measured by electronic drug monitoring (EDM) [ Time Frame: Through Week 48 ] [ Designated as safety issue: No ]
  • Self-reported number of doses missed in last 30 days and self-reported adherence rating scale [ Time Frame: Through Week 48 ] [ Designated as safety issue: No ]
  • Proportion of doses taken as measured by EDM the day of and day prior to a sexual exposure as detected by SMS assessment [ Time Frame: Through Week 48 ] [ Designated as safety issue: No ]
  • Selected drug concentration measurements in stored plasma samples [ Time Frame: Through Week 48 ] [ Designated as safety issue: No ]
  • Self-reported quality of life indicators over time using a standardized assessment tool [ Time Frame: Through Week 48 ] [ Designated as safety issue: No ]
  • Self-reported sexual behavior over time using a standardized assessment tool [ Time Frame: Through Week 48 ] [ Designated as safety issue: No ]
  • Occurrence of Grade 1 clinical (non-laboratory) AEs that lead to a temporary or permanent hold of study drug [ Time Frame: Through Week 48 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 600
Study Start Date: June 2012
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
MVC 300 mg plus FTC placebo and TDF placebo orally once daily
Drug: Maraviroc
300-mg tablet, once daily, from Week 0 through Week 48
Other Names:
  • Selzentry
  • MVC
Other: Emtricitabine placebo
Once daily from Week 0 through Week 48
Other: Tenofovir disoproxil fumarate placebo
Once daily from Week 0 through Week 48
Experimental: Arm 2
MVC 300 mg plus FTC 200 mg and TDF placebo orally once daily
Drug: Maraviroc
300-mg tablet, once daily, from Week 0 through Week 48
Other Names:
  • Selzentry
  • MVC
Drug: Emtricitabine
200-mg capsule, once daily, from Week 0 through Week 48
Other Names:
  • Emtriva
  • FTC
Other: Tenofovir disoproxil fumarate placebo
Once daily from Week 0 through Week 48
Experimental: Arm 3
MVC 300 mg plus FTC placebo and TDF 300 mg orally once daily
Drug: Maraviroc
300-mg tablet, once daily, from Week 0 through Week 48
Other Names:
  • Selzentry
  • MVC
Drug: Tenofovir disoproxil fumarate
300-mg tablet, once daily, from Week 0 through Week 48
Other Names:
  • Viread
  • TDF
Other: Emtricitabine placebo
Once daily from Week 0 through Week 48
Experimental: Arm 4
MVC placebo plus FTC 200 mg and TDF 300 mg orally once daily
Drug: Emtricitabine
200-mg capsule, once daily, from Week 0 through Week 48
Other Names:
  • Emtriva
  • FTC
Drug: Tenofovir disoproxil fumarate
300-mg tablet, once daily, from Week 0 through Week 48
Other Names:
  • Viread
  • TDF
Other: Maraviroc placebo
Once daily from Week 0 through Week 48

Detailed Description:

Several clinical trials are currently under way evaluating the safety and efficacy of ARV-based PrEP for preventing HIV infection. In 2010, the results of the first efficacy trial of ARV-based PrEP showed 44% fewer HIV infections among study participants receiving the study drugs (TDF and FTC) than among those receiving placebo. Although these results are promising, concerns about poor adherence, drug resistance, and toxicity prompt further exploration of ARV PrEP regimens. This trial will evaluate the safety and tolerability of PrEP using four ARV regimens in reducing HIV transmission in at-risk men who have sex with men and in at-risk women.

Participants will be randomly assigned to one of four arms: Arm 1, Arm 2, Arm 3, or Arm 4. Arm 1 will receive MVC, FTC placebo, and TDF placebo orally once daily from Week 0 through 48. Arm 2 will receive MVC, FTC, and TDF placebo orally once daily from Week 0 through 48. Arm 3 will receive MVC, FTC placebo, and TDF orally once daily from Week 0 through 48. Participants in Arm 4 will receive MVC placebo, FTC, and TDF orally once daily from Week 0 through 48.

Study visits will occur at enrollment and Weeks 2, 4, 8, 16, 24, 32, 40, 48, and 49. All study visits will include a physical examination, blood collection and storage, and HIV counseling and testing. Select study visits will include adherence counseling, surveys, behavioral assessments (including sexual behavioral assessments), urine collection, and dual-energy x-ray absorptiometry (DXA). Participants will also undergo sexual behavioral assessments randomly 12 to 13 times through Week 48 via short message service (SMS). Some female participants may opt into taking part in an interview at Week 48.

Participants who enroll in this study may also consent to be a part of two subset evaluations as part of this study: the Drug Interaction Subset or the Tissue Subset. Enrollment in these subsets will involve additional study procedures. The Drug Interaction Subset will undergo blood collection before and after a directly observed dose of study drug at the Week 2 visit. Participants in the Tissue Subset will take part in additional study procedures at select visits, including blood collection, hair collection, and rectal tissue and fluid collection (required for men; optional for women). Women involved in the Tissue Subset will also undergo cervical tissue and cervicovaginal fluid collection at select visits.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • For participants in the men's component of the study, born male. For participants in the women's component of the study, born female.
  • 18 years or older at the time of screening
  • Willing to provide informed consent for the study
  • Able to read at a level required for the study components (e.g., computer-assisted self-interview [CASI] and short message service [SMS], per the judgment of the study investigator)
  • For men, a history of receptive or insertive anal intercourse without use of condoms with at least one HIV-infected male partner or male partner of unknown HIV serostatus within 90 days of study entry (provided by self-report)
  • For women, a history of vaginal intercourse or receptive anal intercourse without use of condoms with at least one HIV-infected male partner or male partner of unknown HIV serostatus within 90 days of study entry (provided by self-report)
  • The following laboratory values must be from specimens obtained within 45 days prior to study enrollment: Nonreactive HIV test results (more information on this criterion can be found in the protocol); hemoglobin (men) greater than 11 g/dL; hemoglobin (women) greater than or equal to 10.5 g/dL; absolute neutrophil count greater than 750 cells/mm^3; platelet count greater than or equal to 100,000/mm^3; for men and women, calculated creatinine clearance greater than or equal to 70 mL/minute using the Cockcroft-Gault equation; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than 3 times the upper limit of normal (ULN); total bilirubin less than 2.5 ULN; urine protein less than 2+; and hepatitis B surface antigen (HBsAg) negative.
  • No alcohol or substance use that, in the opinion of the study investigator, would interfere with the conduct of the study (e.g., provided by self-report or found upon medical history and examination or in available medical records)
  • No medical condition that, in the opinion of the study investigator, would interfere with the conduct of the study (e.g., provided by self-report or found upon medical history and examination or in available medical records)
  • Willing to undergo all required study procedures (including sexual assessment by CASI, use of the drug monitoring device, and SMS [i.e., texting])
  • For all women participants: If of reproductive potential (defined as girls who have reached menarche and pre-menopausal women who have not had a sterilization procedure per self-report (e.g., hysterectomy, bilateral oophorectomy, tubal ligation or salpingectomy), must have a negative serum or urine pregnancy test performed within 48 hours before initiating the protocol-specified medication(s). More information on this criterion can be found in the protocol.
  • For all women participants: If participating in sexual activity that could lead to pregnancy, must agree to use a form of contraception from the following list during the trial and for 30 days after stopping the study medication: condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, IUD, or hormone-base contraceptive.

Inclusion Criteria for the Tissue Subset:

  • For men and women participating in the rectal component, willing to abstain from receptive anal intercourse and practices involving insertion of anything in the rectum (drug, enema, penis, or sex toy) for 3 days prior to rectal biopsy and for 7 days post-biopsy, to minimize risk of HIV-1 infection and bleeding complications after each procedure
  • For women participating in the vaginal component, willing to abstain from vaginal intercourse and practices involving insertion of anything in the vagina (drug, douche, penis, or sex toy) for 3 days prior to cervical biopsy and for 7 days post-biopsy, to minimize risk of HIV-1 infection and bleeding complications after each procedure
  • For women only, per participant report at screening, usual menstrual cycle with at least 21 days between menses (does not apply to participants who report using a progestin-only method of contraception at screening, e.g., Depo-Provera)
  • For women, satisfactory Pap results in the 12 calendar months prior to enrollment consistent with Grade 0 according to the Female Genital Grading Table for Use in Microbicide Studies Addendum 1 to the DAIDS Table for Grading Adult and Pediatric Adverse Events, Version 1.0, December 2004 (Clarification dated August 2009), or satisfactory evaluation with no treatment required of Grade 1 or higher Pap result per American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines in the 12 calendar months prior to enrollment. If there is no document of satisfactory Pap results, the participant should be offered to have the test performed by the site prior to the enrollment visit. If they refuse, they are not eligible.

Exclusion Criteria:

  • One or more reactive HIV test results at screening or enrollment, even if HIV infection is not confirmed
  • Coenrollment in any other HIV interventional research study (provided by self-report or other available documentation) or prior enrollment and receipt of active arm (i.e., NOT a placebo) of an HIV vaccine trial (provided by available documentation)
  • Use of ARV therapy (e.g., for post-exposure prophylaxis [PEP] or PrEP) in the 90 days prior to study entry
  • Prior history of a gastrectomy, colostomy, ileostomy, or any other procedure altering the gastrointestinal tract or drug absorption (provided by self-report or obtained from medical history or records)
  • Receipt of prohibited medications as described in the study drug package inserts or listed in the Study-Specific Populations (SSP) Manual (provided by self-report or obtained from medical history or medical records)
  • Ongoing intravenous drug use: episodic use or any use in the past 90 days (as assessed by the study investigator)
  • Known medical history of allergy to soy (soya or soybeans) or peanuts
  • Weight exceeding 300 pounds (exceeds weight limit of DXA scanners)
  • For women, pregnancy or currently breastfeeding

Exclusion Criteria for the Tissue Subset:

For Men and Women:

  • The following applies to men, and only to women who opt for rectal sampling: Abnormalities of the colorectal mucosa or significant colorectal symptom(s), which in the opinion of the study investigator represent a contraindication to biopsy (including but not limited to presence of any unresolved injury, infectious or inflammatory condition of the local mucosa, and presence of symptomatic external hemorrhoids)
  • Per participant report at screening, anticipated use and/or unwillingness to abstain from the following medications during the period of study participation: Heparin, including Lovenox®, Warfarin, Plavix® (clopidogrel bisulfate), or any other drugs that are associated with increased risk of bleeding following biopsy procedures in the opinion of the study investigator
  • The following applies to men, and only to women who opt for rectal sampling: Per participant report at screening, anticipated use and/or unwillingness to abstain from rectally administered medications (including over-the-counter products) for 3 days prior to rectal biopsies and for 7 days after biopsies
  • Per participant report at screening, anticipated use and/or unwillingness to abstain from the following medications for a period of 10 days before a biopsy procedure: aspirin (daily use of low-dose aspirin [no more than 81 mg] is allowed at the discretion of the Investigator of Record) or non-steroidal anti-inflammatory drugs (NSAIDS)
  • Abnormal laboratory results for coagulation tests that may indicate an increased risk of bleeding (in the opinion of the investigators)
  • Active untreated syphilis, gonorrhea, or chlamydia infection

For Women Only:

  • Carcinoma in situ of the cervix or invasive cervical cancer. Abnormalities of the vaginal mucosa or significant vaginal symptom(s), which in the opinion of the study investigator represent a contraindication to biopsy (including but not limited to presence of any unresolved injury, and infectious or inflammatory condition of the local mucosa).
  • Hysterectomy
  • Per participant report at screening, anticipated use and/or unwillingness to abstain from vaginally administered medications (including over-the-counter products) and vaginal douching for 3 days prior to cervical biopsies and for 7 days after biopsies
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01505114

Locations
United States, California
UCLA CARE Center CRS Recruiting
Los Angeles, California, United States, 90035
Contact: Arezou S. Akha, M.D., M.S.    310-557-3798    asadighi@mednet.ucla.edu   
Bridge HIV CRS Recruiting
San Francisco, California, United States, 94143
Contact: Theresa M. Wagner, MPH    415-437-7436    Theresa.Wagner@sfdph.org   
United States, District of Columbia
George Washington Univ. CRS Recruiting
Washington, District of Columbia, United States, 20001
Contact: Christopher C. Watson    202-652-4711    cclwat@gwu.edu   
United States, Maryland
Johns Hopkins University CRS Recruiting
Baltimore, Maryland, United States, 21205
Contact: Ilene Wiggins, R.N.    410-614-2766    iwiggin1@jhmi.edu   
United States, Massachusetts
The Fenway Institute CRS Withdrawn
Boston, Massachusetts, United States, 02215
Fenway Health (FH) CRS Recruiting
Boston, Massachusetts, United States, 02215-4302
Contact: Marcy Gelman, R.N., M.S.N., M.P.H., A.R.N.P.    617-927-6021    mgelman@fenwayhealth.org   
United States, New Jersey
New Jersey Medical School Clinical Research Center CRS Recruiting
Newark, New Jersey, United States, 07103
Contact: Janet Forcht, R.N.    973-972-1005    jf711@njms.rutgers.edu   
New Jersey Medical School CRS (El-Sadr CTU) Withdrawn
Newark, New Jersey, United States, 07103
United States, New York
Weill Cornell Uptown CRS Not yet recruiting
New York, New York, United States, 10065
Contact: Valery Hughes    212-746-4393    Vah9001@med.cornell.edu   
Weill Cornell Chelsea CRS Recruiting
New York, New York, United States, 10011
Contact: Todd Stroberg, RN, BSN    212-746-7198    tstrober@med.cornell.edu   
United States, North Carolina
Chapel Hill CRS Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Susan Pedersen    919-966-6713    spederse@med.unc.edu   
Wake County Health and Human Services CRS Recruiting
Raleigh, North Carolina, United States, 27630-4049
Contact: Susan Pedersen    919-966-6713    spederse@med.unc.edu   
United States, Ohio
Case Clinical Research Site Recruiting
Cleveland, Ohio, United States, 44106
Contact: Jane Baum, RN    216-844-2546    jb@clevelandactu.org   
United States, Pennsylvania
Penn Therapeutics, CRS Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Joseph Quinn, R.N., B.S.N.    215-349-8093    joseph.quinn@uphs.upenn.edu   
University of Pittsburgh CRS Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Carol Oriss, R.N., B.S.N.    412-383-1434    orissca@upmc.edu   
United States, Washington
University of Washington AIDS CRS Recruiting
Seattle, Washington, United States, 98104-9929
Contact: Christine Jonsson    206-744-8886    cjonsson@u.washington.edu   
Puerto Rico
Puerto Rico AIDS Clinical Trials Unit CRS Recruiting
San Juan, Puerto Rico, 00935
Contact: Sylvia I. Davila Nieves, M.Sc.    787-767-9192    sylvia.davila1@upr.edu   
Sponsors and Collaborators
HIV Prevention Trials Network (HPTN)
AIDS Clinical Trials Group (ACTG)
Investigators
Study Chair: Roy M. Gulick, MD, MPH Weill Medical College of Cornell University
  More Information

Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01505114     History of Changes
Other Study ID Numbers: HPTN 069/A5305 (NEXT Prep), 11789, HPTN 069/A5305, HPTN 069, HPTN 069/NEXT Prep
Study First Received: January 4, 2012
Last Updated: November 4, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
HIV Prevention
PrEP
Maraviroc

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
Communicable Diseases
HIV Infections
Infection
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Emtricitabine
Tenofovir
Tenofovir disoproxil
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014