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Emtricitabine/Tenofovir Disoproxil Fumarate for HIV Prevention in Men (iPrEx)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00458393
Recruitment Status : Completed
First Posted : April 10, 2007
Results First Posted : January 24, 2018
Last Update Posted : January 24, 2018
Sponsor:
Collaborator:
Bill and Melinda Gates Foundation
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE April 6, 2007
First Posted Date  ICMJE April 10, 2007
Results First Submitted Date  ICMJE December 27, 2016
Results First Posted Date  ICMJE January 24, 2018
Last Update Posted Date January 24, 2018
Study Start Date  ICMJE June 2007
Actual Primary Completion Date February 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 19, 2018)
  • HIV Seroconversion [ Time Frame: Monthly follow-up through a median of 1.2 years ]
    Confirmed HIV infection
  • Grade 1 or Higher Creatinine Toxicity [ Time Frame: Duration of follow-up, median 1.2 years ]
    Creatinine which reach grade 1 (mild, 1.1 to 1.3 local upper limit of normal) or higher by the US Division of AIDS grading table (version 1) or a 50% increase in creatinine from the baseline value. The DAIDS table can be found at https://rsc.tech-res.com/docs/default-source/safety/table_for_grading_severity_of_adult_pediatric_adverse_events.pdf
  • Grade 3 or Higher Phosphorous Toxicity [ Time Frame: The entire follow-up period, median 1.2 years ]
    Grade 3 or higher phosphorous toxicity (hypophosphatemia) by the Division of AIDS Grading Table (severe, level at or below 1.9 mg/dL)
  • Grade 2, 3, or 4 Laboratory Adverse Events [ Time Frame: Entire follow-up, median 1.2 years ]
    Number of participants with at least one Grade 2, 3, or 4 laboratory adverse events (moderate, severe of life threatening based one the US Division of AIDS Grading of adverse events, version 1.0). The table can be found at https://rsc.tech-res.com/docs/default-source/safety/table_for_grading_severity_of_adult_pediatric_adverse_events.pdf
  • Grade 2, 3, or 4 Clinical Adverse Events [ Time Frame: Entire follow-up, median 1.2 years ]
    Number of participants with at least 1 Grade 2, 3, or 4 clinical adverse events (moderate, severe of life threatening based one the US Division of AIDS Grading of adverse events, version 1.0). The table can be found at https://rsc.tech-res.com/docs/default-source/safety/table_for_grading_severity_of_adult_pediatric_adverse_events.pdf
Original Primary Outcome Measures  ICMJE
 (submitted: April 6, 2007)
  • HIV infection as measured by seroconversion
  • Grade 1 or higher creatinine toxicity
  • Grade 3 or higher phosphorus toxicity
  • Grade 2, 3,or 4 laboratory or clinical adverse events
  • HIV seroconversion
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 19, 2018)
  • Hepatitis Flares Among Hepatitis B Virus (HBV) Infected Persons During and After Chemoprophylaxis [ Time Frame: Quarterly lab tests through a median follow-up of 1.2 years ]
    A hepatic flare is defined as an increase in alanine transaminase or aspartate transaminase to >5 fold upper limit of normal at any visit, or an increase to >2.5 fold upper limit of normal for 3 months, within 24 weeks of permanently stopping study drug. More details in https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752387/
  • Percentage Change in Bone Mineral Density [ Time Frame: baseline and week 24. ]
    % Change from baseline in bone mineral density (100 * [(value at 24 weeks- value at baseline)/ (value at baseline)]) in in hip and L1-L4 spine by dual-energy x-ray absorptiometry
  • Percentage Change in Body Fat [ Time Frame: Baseline and Week 24 ]
    Percentage Change (100 * [(value at 24 weeks- value at baseline)/ (value at baseline)]) in Body Fat from Baseline by dual-energy x-ray absorptiometry
  • Percentage Change in Fasting Triglycerides [ Time Frame: Baseline and Week 24 ]
    Percentage Change (Percentage Change (100 * [(value at 24 weeks- value at baseline)/ (value at baseline)]) in Triglycerides from Baseline from a fasting sample.
  • Percent Change in Total Cholesterol [ Time Frame: Baseline and Week 24 ]
    Percent change (100 * [(value at 24 weeks- value at baseline)/ (value at baseline)]) in fasting total cholesterol from baseline
  • Viral Load Among HIV Infected Participants [ Time Frame: At the time closest to HIV detection ]
    HIV-RNA in log10 units among HIV infected participants at the time closest to HIV detection
  • Among HIV Infected Participants Drug Resistance [ Time Frame: at the time of HIV acquisition ]
    Genotypic resistance by clinical assays among the seroconverters from baseline to the end of the study treatment period
  • CD4 Count Among HIV Infected Participants [ Time Frame: at the time infection was detected ]
    CD4 cell count for HIV infected participants during the trial
  • Proportion of Missed Doses by Pill Count [ Time Frame: At 24 weeks ]
    Estimated proportion of missed doses by pill count (assuming pills taken in unreturned bottles)
  • Percentage of Missed Doses by Estimate During CASI Interview [ Time Frame: Week 24 ]
    Percentage of missed doses by estimate during computer assisted structured interview
  • Number of Condomless Sexual Partners With HIV Positive or Unknown Status [ Time Frame: At 24 weeks ]
    Participants self-report of the number of sexual partners with HIV positive or unknown status in the previous 12 weeks with whom they had condomless anal sex
  • Total Number of Sexual Partners [ Time Frame: 24 weeks ]
    Self-reported total number of sexual partners in the previous 12 weeks.
  • Condomless Receptive Anal Intercourse in the Previous 12 Weeks With Any Partners Regardless of Status. [ Time Frame: At 24 weeks ]
    Self-reported condomless receptive anal intercourse in the previous 12 weeks with any partners regardless of status.
  • Incidence of Confirmed Syphilis During Follow-Up [ Time Frame: All Follow-Up median of 1.2 years of follow-up ]
    Number of participants who have at least 1 confirmed syphilis infection during the study
  • Incidence of HSV-2 During the Follow-up Period [ Time Frame: Total study follow-up, a median of 1.2 years ]
    Incidence of HSV-2 during the follow-up period among those HIV-2 negative at baseline
  • Diagnosis of Gonorrhea During the Follow-up Period [ Time Frame: All of follow-up period, median of 1.2 years ]
    Diagnosis of gonorrhea during the follow-up period by PCR
Original Secondary Outcome Measures  ICMJE
 (submitted: April 6, 2007)
  • Hepatitis flares among hepatitis B virus (HBV) infected persons during and after chemoprophylaxis
  • Changes in bone mineral density or body fat distribution
  • among HIV infected participants: viral load, drug resistance, and CD4 cell counts
  • Attitudinal and behavioral correlates of chemoprophylaxis failure or success
  • risk behavior including condom use before, during, and after use of study medication
  • the prevalence of sexually transmitted infections (STIs) before, during, and after use of study medication
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Emtricitabine/Tenofovir Disoproxil Fumarate for HIV Prevention in Men
Official Title  ICMJE Chemoprophylaxis for HIV Prevention in Men
Brief Summary The purpose of this study is to determine whether daily use of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) can prevent HIV infection in men who also receive HIV counseling, condoms, and treatment for other sexually transmitted infections (STIs).
Detailed Description

The Joint United Nations Programme on AIDS estimates that 14,000 persons are newly infected with HIV every day worldwide; one half of these infections occur in people between the ages of 15 and 24. New infections occur despite widespread awareness of the modes of HIV transmission and the protection afforded by condom use. Effective interventions for HIV prevention are urgently needed. This study will evaluate the safety and efficacy of chemoprophylaxis for HIV prevention in men who have sex with men (MSM) who are at high risk for HIV infection despite using condoms, receiving HIV counseling, and receiving treatment for STIs, particularly hepatitis B virus (HBV) infection. A daily combination dose of emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) has been selected for evaluation because it has a well-established safety record in previous studies and was demonstrated to be effective for HIV prevention in primate models. These medications have long half-lives that allow daily dosing and do not have known interactions with hormonal contraception, methadone, or tuberculosis therapies.

Once on the study drug, participants will be followed for a variable length of time, starting within 4 weeks of their screening visit and lasting up to 144 weeks. All participants will be followed for at least 8 weeks after stopping study drug. Participants who are reactive to a Hepatitis B surface antigen (HBsAg) test will be followed for hepatic flares for 16 additional weeks for a total of 24 weeks after stopping study drug. If enrolled in the optional substudy of bone mineral density, fat distribution, and fasting lipids, the participant will be asked to return for one additional visit 24 weeks after stopping study drug. Participants who HIV seroconvert during their participation will also be followed until the end of the study.

All study visits will be at 4 week intervals. At study entry, high risk, HIV uninfected MSM will be randomly assigned to receive either daily FTC/TDF or placebo, in addition to standard HIV counseling, condoms, and sexually transmitted infection (STI) management. The study will closely monitor biological and behavioral safety, including careful analysis of drug resistance, kidney and liver function, and risk behavior.

At the screening visit, participants will undergo HIV antibody and HBV testing, a medical history, a medical exam, blood and urine collection, risk behavior assessment, and STI testing. At study entry, participants will be given study medication; tested for HCV; and offered the HBV vaccine, if applicable. At all study visits, there will be HIV antibody testing, pill counts, adherence checks, study medication distribution, HIV counseling, and condom distribution. A medical history and blood will be taken on selected visits, along with STI testing and treatment if needed. Testing and treatment of STIs will be provided at no cost to the participant.

All study participants will be encouraged to join a substudy that will assess interactions between HBV infection, bone mineral density and fat distribution, and immune function. If enrolled in the substudy, the participant will be asked to return for one additional visit 24 weeks after stopping the study medication. All participants in the substudy will undergo dual energy x-ray absorptiometry (DEXA) scans, and HIV infected participants will undergo additional blood collection.

Sites will have the option of participating in the following four substudies:

The Hair Substudy: Participants who are receiving FTC/TDF will be eligible to enroll. At each 12-week follow-up study visit, hair samples will be collected and questionnaires will be completed.

The Urine Substudy: For all participants who elect to enroll in this substudy, additional testing will occur on blood and urine samples collected at each 24-week follow-up visit. An additional urine collection will occur 8 weeks after participants stop receiving FTC/TDF.

The Semen Substudy: Participants who seroconvert during the study may elect to participate in this substudy. One semen sample will be collected at participants' next study visit when plasma viral load testing is performed.

The Gonorrhea and Chlamydia Substudy: Participants in this substudy will undergo rectal and oropharyngeal swab procedures and urine collection at the 24-week study visit.

After the randomized phase ends, if the daily oral FTC/TDF arm is shown to be beneficial and safe, participants will be given the option of participating in an open label extension phase. During this extension phase, study participants will receive daily oral open-label FTC/TDF, in addition to standard counseling, condoms, and STI management.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Condition  ICMJE HIV Infections
Intervention  ICMJE
  • Drug: daily TDF/FTC
    daily oral medication
    Other Name: truvada
  • Drug: Placebo
    daily oral medication
Study Arms  ICMJE
  • Experimental: TDF/FTC
    Drug. Daily oral tablet of co-formulated 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate (TDF/FTC).
    Intervention: Drug: daily TDF/FTC
  • Placebo Comparator: Placebo
    Drug. Daily oral placebo
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 19, 2018)
2499
Original Enrollment  ICMJE
 (submitted: April 6, 2007)
1400
Actual Study Completion Date  ICMJE February 2014
Actual Primary Completion Date February 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male sex (at birth)
  • HIV uninfected
  • Age having reached the local age of consent
  • High risk for HIV infection including any of the following: 1) No condom use during anal intercourse with a male HIV-positive partner or a male partner of unknown HIV status during the last 6 months; (2) anal intercourse with more than 3 male sex partners during the last 6 months; (3) exchange of money, gifts, shelter, or drugs for anal sex with a male partner during the last 6 months; (4) sex with a male partner and STI diagnosis during the last 6 months or at screening, or (5) sexual partner of an HIV-infected man with whom condoms are not consistently used in the last 6 months.
  • Able to provide a street address of residence for themselves and one personal contact who would know their whereabouts during the study period
  • Healthy enough to work, as indicated by score of 80 or greater on the Karnofsky scale
  • Certain laboratory values
  • A urine dipstick with a negative or trace result for both glucose and protein within 28 days of enrollment.
  • Ability to understand and local language for which an informed consent form has been approved by a local IRB and registered with the study sponsor.

Inclusion Criteria for Open-Label Extension:

  • Participated in a randomized, placebo-controlled, PrEP trail
  • Has been unblinded
  • Has provided informed consent

Exclusion Criteria:

  • Previously diagnosed active and serious infections, including tuberculosis infection, osteomyelitis, or infections requiring parenteral antibiotic therapy
  • Active clinically significant medical problems including heart disease (e.g., symptoms of ischemia, congestive heart failure, arrhythmia), lung disease (steroid-dependent chronic obstructive pulmonary disease), diabetes requiring hypoglycemic medication, or previously diagnosed cancer expected to require further treatment
  • Acute HBV infection at the screening visit or presence of treatment indications for hepatitis B based on local practice standards; or clinical signs of hepatic cirrhosis
  • History of pathological bone fractures not related to trauma
  • Receiving ongoing therapy with certain HIV/AIDS-related medications or other medications as determined by the investigator
  • Definitely or possibly received an anti-HIV vaccine while participating in a blinded clinical trial
  • Current alcohol or drug use that, in the opinion of the investigator, may interfere with the study
  • Current participation in a clinical trial or cohort study other than sub-studies of this protocol
  • Any condition at enrollment that, in the opinion of the investigator, would make participation in the study unsafe or would interfere with the study
  • Sites may utilize additional criteria that restrict enrollment to a subset of people who meet the protocol-defined enrollment criteria.

Exclusion Criteria for Open-Label Extension:

- Site leadership believes participant will have difficulty completing requirements

Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil,   Ecuador,   Peru,   South Africa,   Thailand,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00458393
Other Study ID Numbers  ICMJE CO-US-104-0288
10445 ( Registry Identifier: DAIDS ES )
1U01AI064002 ( U.S. NIH Grant/Contract )
iPrEx ( Other Identifier: Study team )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE Bill and Melinda Gates Foundation
Investigators  ICMJE
Principal Investigator: Robert M. Grant, MD, MPH J. David Gladstone Institutes, University of California San Francisco
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date December 2016

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