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

Sponsored by:	Family Health International
Information provided by:	Family Health International
ClinicalTrials.gov Identifier:	NCT00625404

Purpose

This Phase III, double-blind, randomized, placebo-controlled trial will enroll an estimated 3900 HIV-negative women from 6 sites in 4 countries (Kenya, Malawi, Tanzania and South Africa). The study's purpose is 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 includes HIV-antibody-negative women between the ages of 18-35 who are at risk of HIV acquisition through sexual intercourse. Each participant will be 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 will receive risk reduction counseling and condoms. Women must be using a study-approved effective non-barrier contraceptive method at the time of enrollment and will be asked to do so for the whole period they are on study drug. They will receive contraceptive counseling throughout the study. Any diagnosed, treatable sexually transmitted infection will be treated free of charge.

Study duration is approximately 37-40 months at each site; participant screening and enrollment is anticipated to take approximately 12-16 months. After enrollment, each participant will be followed every four weeks for 52 weeks on study drug. All participants will be followed for an additional four weeks after study drug has been stopped. Participants at risk for hepatitis B virus (HBV) flare will be followed every four weeks for at least 12 weeks after stopping study product. Participants who acquire HIV infection during the study will stop taking the study drug at the time of HIV diagnosis, will be followed for 52 weeks post diagnosis and will be referred for care and treatment. Participants who become pregnant will stop taking the study drug but will continue follow-up visits. After the study, incidence rates of HIV infection will be compared between the two groups (active drug and placebo) using the intent-to-treat principle.

Condition	Intervention	Phase
HIV Infections	Drug: Truvada® Drug: Placebo	Phase III

MedlinePlus related topics: AIDS Hepatitis

Drug Information available for: Magnesium Starch Lactose Cellulose Cellulose sodium phosphate Phosphocellulose Tenofovir Tenofovir disoproxil Tenofovir Disoproxil Fumarate Truvada Carboxymethylcellulose Aluminum monostearate Calcium stearate n-Octadecanoic acid Potassium benzoate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Safety/Efficacy Study
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

Further study details as provided by Family Health International:

Primary Outcome Measures:

Combined incidence of HIV-1 and HIV-2 infection as determined by detection of HIV antibodies using HIV rapid tests [ Time Frame: 29 months per site ] [ Designated as safety issue: Yes ]
Incidence of confirmed Grade 2 or higher serum creatinine toxicity, and Grade 3 or higher AST, ALT, or phosphorus toxicity during and 4 weeks after study product administration [ Time Frame: 41 months per site ] [ Designated as safety issue: Yes ]
Frequency and nature of adverse events (AEs) during and within 4 weeks after study product administration [ Time Frame: 41 months per site ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Viral load and CD4+ T cell counts at the time of HIV diagnosis and at 4, 8, 12, 16, 24, 36 and 52 weeks later [ Time Frame: 37-41 months per site ] [ Designated as safety issue: Yes ]
FTC and/or tenofovir resistance at the time of HIV diagnosis and 4 weeks later. If resistance is present, testing will be repeated at weeks 12, 24, 36 and 52 as necessary (resistance testing will stop if no resistance is detected) [ Time Frame: 37-41 months per site ] [ Designated as safety issue: Yes ]
Bone mineral density by dual-energy x-ray absorptiometry (DEXA) in a subset of participants (N=200) at 24 and 52 weeks during study product administration [ Time Frame: 35 months per site ] [ Designated as safety issue: Yes ]
Incidence of pregnancy loss, prematurity, low birth weight, and congenital abnormalities [ Time Frame: 37-50 months per site ] [ Designated as safety issue: Yes ]
Pill counts and participant report of adherence to once-daily pill taking [ Time Frame: 29 months per site ] [ Designated as safety issue: No ]
Participant report of the number of sexual partners and frequency of unprotected sexual acts over time [ Time Frame: 29 months per site ] [ Designated as safety issue: No ]
Participant report of sexual behaviors and sex partner characteristics by participants who seroconvert and matched HIV negative participants [ Time Frame: 37-40 months per site ] [ Designated as safety issue: No ]

Estimated Enrollment:	3900
Study Start Date:	February 2009
Estimated Study Completion Date:	February 2013
Estimated Primary Completion Date:	February 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Truvada® Participants in both study arms will receive risk reduction counseling and condoms.	Drug: Truvada® Truvada® is made by Gilead Sciences, Inc. Truvada® tablets are blue capsule-shaped film-coated tablets containing 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate. Each tablet contains the following inactive ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and pregelatinized starch. Dosage for this study is one tablet per day, taken orally as close as possible to twenty-four hours apart. Participants in both study arms will receive risk reduction counseling and condoms.
2: Placebo Comparator Placebo tablets are identical to Truvada tablets in taste and appearance; however, they contain no active ingredients. Placebo tablets contain the same inactive ingredients as Truvada (croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose and pregelatinized starch), plus denatonium benzoate to provide a bitter taste to match the active tablets. Participants in both study arms will receive risk reduction counseling and condoms.	Drug: Placebo Placebo tablets are identical to Truvada tablets in taste and appearance; however, they contain no active ingredients. Placebo tablets contain the same inactive ingredients as Truvada (croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose and pregelatinized starch), plus denatonium benzoate to provide a bitter taste to match the active tablets. Participants in both study arms will receive risk reduction counseling and condoms.

Arms

Assigned Interventions

1: Experimental

Truvada®

Participants in both study arms will receive risk reduction counseling and condoms.

Drug: Truvada®

Truvada® is made by Gilead Sciences, Inc. Truvada® tablets are blue capsule-shaped film-coated tablets containing 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate. Each tablet contains the following inactive ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and pregelatinized starch. Dosage for this study is one tablet per day, taken orally as close as possible to twenty-four hours apart.

Participants in both study arms will receive risk reduction counseling and condoms.

2: Placebo Comparator

Placebo tablets are identical to Truvada tablets in taste and appearance; however, they contain no active ingredients. Placebo tablets contain the same inactive ingredients as Truvada (croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose and pregelatinized starch), plus denatonium benzoate to provide a bitter taste to match the active tablets.

Participants in both study arms will receive risk reduction counseling and condoms.

Drug: Placebo

Placebo tablets are identical to Truvada tablets in taste and appearance; however, they contain no active ingredients. Placebo tablets contain the same inactive ingredients as Truvada (croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose and pregelatinized starch), plus denatonium benzoate to provide a bitter taste to match the active tablets.

Participants in both study arms will receive risk reduction counseling and condoms.

Detailed Description:

This Phase III, double-blind, randomized, placebo-controlled trial will enroll an estimated 3900 HIV-negative women from 6 sites in 4 countries (Kenya, Malawi, Tanzania and South Africa). The study's purpose is 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 includes HIV-antibody-negative women between the ages of 18-35 who are at risk of HIV acquisition through sexual intercourse. Each participant will be 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 will receive risk reduction counseling and condoms. Women must be using a study-approved effective non-barrier contraceptive method at the time of enrollment and will be asked to do so for the whole period they are on study drug. They will receive contraceptive counseling throughout the study. Any diagnosed, treatable sexually transmitted infection will be treated free of charge.

Study duration is approximately 37-40 months at each site; participant screening and enrollment is anticipated to take approximately 12-16 months. After enrollment, each participant will be followed every four weeks for 52 weeks on study drug. All participants will be followed for an additional four weeks after study drug has been stopped. Participants at risk for Hepatitis B Virus (HBV) flare will be followed every four weeks for at least 12 weeks after stopping study product. Participants who acquire HIV infection during the study will stop taking the study drug at the time of HIV diagnosis, and will be followed for 52 weeks post diagnosis and will be referred for care and treatment. Participants who become pregnant will stop taking the study drug but will continue follow-up visits. After the study, incidence rates of HIV infection will be 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:

Willing and able (see criterion 2) to provide written informed consent to be screened for and to participate in the trial
Able to answer a percentage of informed consent screening (75%) and enrollment (100%) comprehension quiz questions correctly
Between 18-35 years old, inclusive
At higher risk of becoming HIV infected
Have non-reactive HIV rapid test results at the screening and enrollment visits
Willing to participate in all aspects of the study and to comply with study procedures, for up to 56 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
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)
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
Not pregnant or breastfeeding, and does not anticipate a desire for pregnancy during the 52 weeks of on-product participation
Medically eligible at screening including:
- Adequate renal function (serum creatinine < 1.5 mg/dl and creatinine clearance ≥ 60 ml/min estimated by the Cockcroft-Gault creatinine clearance formula
- Adequate hepatic function (hepatic transaminases ALT and AST < 2x upper limit of normal [ULN] [according to local normal ranges])
- HBsAg negative serum phosphorus levels within the normal range (according to local normal ranges)
Not received or receiving an experimental HIV vaccine, participating in another HIV prevention study or participating in any other clinical trial
No clinical signs of liver disease (e.g., ascites, spider angiomata, hepatomegaly, jaundice)
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.
No history of pathological bone fractures
No history of adverse reaction to latex
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00625404

Contacts

Contact: Lut Van Damme, MD, MS, PhD

(703) 516-9779

lvandamme@fhi.org

Locations

Kenya, Nyanza
Bondo Clinic, Bondo District Hospital
Bondo, Nyanza, Kenya
Malawi, Central Region
Research, Training & Care Center - Kamuzu Central Hospital
Lilongwe, Central Region, Malawi
Malawi, Southern Region
University of Malawi College of Medicine - Johns Hopkins University
Blantyre, Southern Region, Malawi
South Africa, Gauteng
Setshaba Research Centre
Pretoria, Gauteng, South Africa
South Africa, Western Cape
University of Cape Town
Cape Town, Western Cape, South Africa
Tanzania
Arusha Clinic, Levolosi Health Center
Arusha, Tanzania

Sponsors and Collaborators

Family Health International

Investigators

Principal Investigator:	Lut Van Damme, MD, MS, PhD	Family Health International
Principal Investigator:	Amy Corneli, PhD, MPH, CHES	Family Health International
Study Director:	Jennifer Deese, MPH	Family Health International

More Information

Responsible Party:	Family Health International ( Dr. Lut Van Damme )
Study ID Numbers:	10015
Study First Received:	February 19, 2008
Last Updated:	January 14, 2009
ClinicalTrials.gov Identifier:	NCT00625404
Health Authority:	United States: Food and Drug Administration; Belgium: Institutional Review Board; Tanzania: National Institute for Medical Research; Tanzania: Food & Drug Administration; Malawi: National Health Sciences Research Committee; South Africa: National Health Research Ethics Council; South Africa: National Health Research Ethics Council; South Africa: Medicines Control Council; Kenya: Ethical Review Committee; Kenya: Ministry of Health; Kenya: Institutional Review Board

Keywords provided by Family Health International:

HIV
HIV Prevention
Oral PrEP
Truvada
women
Tenofovir

TDF
FTC
emtricitabine
hepatitis
HIV Seronegativity

Study placed in the following topic categories:

Virus Diseases
Hepatitis
Sexually Transmitted Diseases, Viral
Emtricitabine
Benzoates
HIV Infections

Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
Tenofovir
Retroviridae Infections
Immunologic Deficiency Syndromes
Tenofovir disoproxil

Additional relevant MeSH terms:

RNA Virus Infections
Slow Virus Diseases
Immune System Diseases
Lentivirus Infections
Infection

ClinicalTrials.gov processed this record on January 16, 2009