FEM-PrEP (Truvada®): Study to Assess the Role of Truvada® in Preventing HIV Acquisition in Women

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
FHI 360
ClinicalTrials.gov Identifier:
NCT00625404
First received: February 19, 2008
Last updated: April 22, 2014
Last verified: April 2014
  Purpose

This Phase III, double-blind, randomized, placebo-controlled trial enrolled HIV-negative women from 4 sites in 3 countries (Kenya, Tanzania, South Africa). The study's purpose was to investigate the safety and effectiveness of a once-daily Truvada® pill (compared with placebo) in preventing HIV among HIV-uninfected women at risk of becoming infected through sexual intercourse.

The study population included HIV-antibody-negative women between the ages of 18-35 who were at risk of HIV acquisition through sexual intercourse. Each participant was randomized to take either a daily single oral tablet of Truvada®, which is a fixed-dose combination of emtricitabine (FTC; 200 mg) and tenofovir disoproxil fumarate (TDF; 300 mg), or an identical placebo.

After enrollment, each participant was followed every four weeks. All participants were followed for an additional eight weeks after study drug was stopped. Incidence rates of HIV infection were compared between the two groups (active drug and placebo) using the intent-to-treat principle.


Condition Intervention Phase
HIV Infections
Drug: Truvada
Other: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Phase 3, Multi-center, Double-blind, Randomized, Placebo-controlled Effectiveness and Safety Study to Assess the Role of Truvada® in Preventing HIV Acquisition in Women

Resource links provided by NLM:


Further study details as provided by FHI 360:

Primary Outcome Measures:
  • HIV Infection [ Time Frame: Cumulative HIV infection between enrollment and 52 weeks ] [ Designated as safety issue: No ]
    HIV Seroconversion, with time to infection refined based on PCR results obtained from stored specimens.

  • Confirmed Grade 2 or Higher Serum Creatinine Toxicity [ Time Frame: cumulative toxicity through 52 weeks of product use and 4 weeks post product ] [ Designated as safety issue: Yes ]
    Repeat specimens were collected to confirm chemistry toxicities. Grade 2 or higher serum creatinine toxicity was defined as ≥1.4 times the upper limit of normal

  • Frequency and Nature of Adverse Events (AEs) During and Within 4 Weeks After Study Product Administration [ Time Frame: 10-26 months per site ] [ Designated as safety issue: Yes ]
  • Confirmed Grade 3 or Higher Reduction in Phosphorus [ Time Frame: Through 52 weeks on product and 4 weeks post-product ] [ Designated as safety issue: Yes ]
    Repeat specimens were collected to confirm chemistry toxicities. Grade 3 phosphorus reduction was defined as ≤2.4mg/dL

  • Confirmed Grade 3 or Higher ALT Elevation [ Time Frame: Through 52 weeks on product and 4 weeks post-product ] [ Designated as safety issue: Yes ]
    Grade 3 or higher ALT elevation was defined as ≥ 2.6 times the upper limit of normal

  • Confirmed Grade 3 or Higher AST Elevation [ Time Frame: Through 52 weeks on product and 4 weeks post-product ] [ Designated as safety issue: Yes ]
    Grade 3 or higher AST elevation was defined as ≥ 2.6 times the upper limit of normal


Secondary Outcome Measures:
  • Plasma HIV RNA Level (HIV-1 Viral Load) [ Time Frame: up to 16 weeks ] [ Designated as safety issue: Yes ]
    Viral load at the time of HIV detection, HIV conversion and through 16 weeks

  • CD4+ T-cell Count [ Time Frame: Up to 16 weeks ] [ Designated as safety issue: Yes ]
    CD4+ T-cell Count at the Time of HIV Seroconversion through 16 weeks

  • FTC and/or Tenofovir Resistance [ Time Frame: up to 52 weeks ] [ Designated as safety issue: Yes ]

    Genotypic resistance to FTC and/or tenofovir at the time of HIV diagnosis and 4 weeks later. If resistance was present, testing was repeated at weeks 12, 24, 36 and 52 as necessary (resistance testing will stop if no resistance is detected).

    participants were classified as having resistance if they had one or more visits in which resistance was detected, even if the resistance became undetectable over time.


  • Pregnancy Complications [ Time Frame: up to 60 weeks ] [ Designated as safety issue: Yes ]
    Reported complications during pregnancy, including spontaneous abortion, vaginal or uterine bleeding, emergency c-section and other complications

  • Pill Counts and Participant Report of Adherence to Once-daily Pill Taking [ Time Frame: Up to 52 weeks ] [ Designated as safety issue: No ]
    Pill counts and participant report of adherence to once-daily pill taking reported as mean days study product could have been used according to pill counts

  • Participant Report of Change in Number of Sexual Partners [ Time Frame: Up to 52 weeks ] [ Designated as safety issue: No ]
    Difference in mean number of reported sexual partners between final study visit and enrollment visit


Enrollment: 2120
Study Start Date: May 2009
Study Completion Date: January 2013
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Truvada Arm
Daily single oral tablet of Truvada (TDF/FTC), a fixed-dose combination of emtricitabine (FTC; 200 mg) and tenofovir disoproxil fumarate (TDF; 300 mg).
Drug: Truvada
Daily single oral tablet of Truvada - a fixed-dose combination of emtricitabine (FTC; 200 mg) and tenofovir disoproxil fumarate (TDF; 300 mg).
Other Name: TDF/FTC - emtricitabine and tenofovir disoproxil fumarate
Placebo Comparator: Placebo Arm
Daily single oral tablet of Placebo. Tablets are identical to Truvada tablets in taste and appearance; however, they contain no active ingredients.
Other: Placebo
Daily single oral tablet of Placebo. Tablets are identical to Truvada tablets in taste and appearance; however, they contain no active ingredients.

Detailed Description:

This Phase III, double-blind, randomized, placebo-controlled trial enrolled HIV-negative women from 4 sites in 3 countries (Kenya, Tanzania, South Africa). The study's purpose was to investigate the safety and effectiveness of a once-daily Truvada® pill (compared with placebo) in preventing HIV among HIV-uninfected women at risk of becoming infected through sexual intercourse.

The study population included HIV-antibody-negative women between the ages of 18-35 who were at risk of HIV acquisition through sexual intercourse. Each participant was randomized to take either a daily single oral tablet of Truvada®, which is a fixed-dose combination of emtricitabine (FTC; 200 mg) and tenofovir disoproxil fumarate (TDF; 300 mg), or an identical placebo. All participants received risk reduction counseling and condoms. Women had to be using a study-approved effective non-barrier contraceptive method at the time of enrollment and were asked to do so for the whole period they were on study drug. They received contraceptive counseling throughout the study. Any diagnosed, treatable sexually transmitted infection was treated free of charge.

After enrollment, each participant was followed every four weeks. All participants were followed for an additional eight weeks after study drug was stopped. Participants at risk for Hepatitis B Virus (HBV) flare were followed every four weeks for 12 weeks after stopping study product. Participants who acquired HIV infection during the study stopped taking the study drug at the time of HIV diagnosis, and will be followed for 52 weeks post diagnosis and were referred for care and treatment. Participants who became pregnant stopped taking the study drug but continued follow-up visits. Incidence rates of HIV infection were compared between the two groups (active drug and placebo) using the intent-to-treat principle.

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Willing and able (see criterion 2) to provide written informed consent to be screened for and to participate in the trial
  2. Able to answer a percentage of informed consent screening (75%) and enrollment (100%) comprehension quiz questions correctly
  3. Between 18-35 years old, inclusive
  4. At higher risk of becoming HIV infected
  5. Have a final negative result according to the site-specific screening HIV testing algorithm and a final negative result at enrollment according to the study HIV testing algorithm
  6. Willing to participate in all aspects of the study and to comply with study procedures, for up to 60 weeks, including:

    • Be randomized
    • Use study product as directed
    • Adhere to follow-up schedule and willing to be contacted by site staff between study visits (by phone and/or in person)
    • Use a study-approved effective non-barrier method of contraception for the duration of the study
    • Take study product, as evidenced by swallowing a vitamin tablet that is similar in size to the study product at enrollment
    • Provide contact information and agrees to some form of contact method throughout the study
  7. Not intending to relocate out of the area for the duration of the study participation and does not have a job or other obligations that may require long absences from the area ( > 1 month at a time)
  8. In general good health and have no condition (social or medical) which, in the opinion of the Site Investigator, would make study participation unsafe or complicate data interpretation
  9. Not pregnant or breastfeeding, and does not anticipate a desire for pregnancy during the 52 weeks of on-product participation
  10. Medically eligible at screening including:

    • Adequate renal function (serum creatinine ≤ upper limit of normal (ULN) of local range and creatinine clearance ≥ 60ml/min estimated by the Cockcroft-Gault Creatinine Clearance Formula
    • Adequate hepatic function (hepatic transaminases ALT and AST < 2x ULN [according to local normal ranges])
    • HBsAg negative
    • Serum phosphorus levels above the lower limit of the local normal range (according to local normal ranges - grade 3 & 4 hypophosphatemia will be excluded even if within normal local ranges)
  11. Not received or receiving an experimental HIV vaccine, participating in another HIV prevention study or participating in any other clinical trial with a biomedical intervention
  12. No clinical signs of liver disease (e.g., ascites, spider angiomata, hepatomegaly, jaundice)
  13. No definite evidence of glycosuria or proteinuria (i.e., no repeated positive [ ≥ + 1 ] urine dipstick). If a urine dipstick is positive for either glucose and/or protein at the first test, a second urine sample will be tested.
  14. No history of pathological bone fractures
  15. No history of adverse reaction to latex
  16. Not taking any of the following medications: nephrotoxic agents; aminoglycoside antibiotics (including gentamicin); intravenous (IV) amphotericin B; cidofovir; cisplatin; foscarnet; IV pentamidine; oral or IV vancomycin; oral or IV gancyclovir; other agents with significant nephrotoxic potential; drugs that slow renal excretion; probenecid; immune system modulators; systemic chemotherapeutic agents (i.e. cancer treatment medications); systemic corticosteroids; interleukin-2 (IL-2); immunomodulators; interferon (alpha, beta, or gamma); other antiretrovirals (including nucleoside analogs, non-nucleoside reverse transcriptase inhibitors, protease inhibitors or investigational antiretroviral agents)
  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: NCT00625404

Locations
Kenya
Bondo Clinic, Bondo District Hospital
Bondo, Nyanza, Kenya
South Africa
Josha Research Center
Josha, Bloemfontein, South Africa
Setshaba Research Centre
Pretoria, Gauteng, South Africa
Tanzania
Arusha Clinic, Levolosi Health Center
Arusha, Tanzania
Sponsors and Collaborators
FHI 360
Investigators
Principal Investigator: Lut Van Damme, MD, MS, PhD FHI 360
Principal Investigator: Amy Corneli, PhD, MPH FHI 360
Study Director: Jennifer Deese, MPH FHI 360
  More Information

Additional Information:
No publications provided by FHI 360

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: FHI 360
ClinicalTrials.gov Identifier: NCT00625404     History of Changes
Other Study ID Numbers: 10015
Study First Received: February 19, 2008
Results First Received: December 9, 2013
Last Updated: April 22, 2014
Health Authority: United States: Food and Drug Administration
Tanzania: Food & Drug Administration
Kenya: Pharmacy and Poisons Board
South Africa: Medicines Control Council

Keywords provided by FHI 360:
Aspartate Aminotransferase (AST)
Alanine Aminotransferase (ALT)
HIV
HIV Prevention
Oral PrEP
Truvada
women
Tenofovir
TDF
FTC
emtricitabine
hepatitis
Pre-exposure Prophylaxis (PrEP)
HIV Seronegativity

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

ClinicalTrials.gov processed this record on July 23, 2014