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 May 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: May 15, 2014
Last verified: May 2014

January 4, 2012
May 15, 2014
June 2012
July 2015   (final data collection date for primary outcome measure)
  • 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 ]
  • Safety as assessed by the occurrence of Grade 3 or higher adverse events [ 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 ]
Complete list of historical versions of study NCT01505114 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Safety as assessed by the occurrence of Grade 2 or higher adverse events [ Time Frame: Through Week 48 ] [ Designated as safety issue: Yes ]
  • Changes in creatinine clearance; fractional excretion of phosphate [ Time Frame: Through Week 49 ] [ Designated as safety issue: No ]
  • Changes in total cholesterol, HDL, 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 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 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, PBMCs, and rectal 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, as measured by electronic drug monitoring [ 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: At Enrollment and throughout study follow-up ] [ Designated as safety issue: No ]
  • Self-reported sexual behavior over time using a standardized assessment tool [ Time Frame: At Enrollment and throughout study follow-up ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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
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

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.

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, 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).

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
HIV Infection
  • 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
  • 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
  • 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 1
    MVC 300 mg plus FTC placebo and TDF placebo orally once daily
    Interventions:
    • Drug: Maraviroc
    • Other: Emtricitabine placebo
    • Other: Tenofovir disoproxil fumarate placebo
  • Experimental: Arm 2
    MVC 300 mg plus FTC 200 mg and TDF placebo orally once daily
    Interventions:
    • Drug: Maraviroc
    • Drug: Emtricitabine
    • Other: Tenofovir disoproxil fumarate placebo
  • Experimental: Arm 3
    MVC 300 mg plus FTC placebo and TDF 300 mg orally once daily
    Interventions:
    • Drug: Maraviroc
    • Drug: Tenofovir disoproxil fumarate
    • Other: Emtricitabine placebo
  • Experimental: Arm 4
    MVC placebo plus FTC 200 mg and TDF 300 mg orally once daily
    Interventions:
    • Drug: Emtricitabine
    • Drug: Tenofovir disoproxil fumarate
    • Other: Maraviroc placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
600
Not Provided
July 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older
Yes
United States,   Puerto Rico
 
NCT01505114
HPTN 069 (NEXT Prep), 11789, HPTN 069/A5305, HPTN 069
Not Provided
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
  • HIV Prevention Trials Network (HPTN)
  • AIDS Clinical Trials Group (ACTG)
Study Chair: Roy M. Gulick, MD, MPH Weill Medical College of Cornell University
National Institute of Allergy and Infectious Diseases (NIAID)
May 2014

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