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

Condition(s) targeted: HIV Infections

Intervention: Truvada® (Drug); Placebo (Drug)

Phase: Phase 3

Status: Not yet recruiting

Sponsored by: Family Health International

Official(s) and/or principal investigator(s):
Lut Van Damme, MD, MS, PhD, Principal Investigator, Affiliation: Family Health International
Amy Corneli, PhD, MPH, CHES, Principal Investigator, Affiliation: Family Health International
Jennifer Deese, MPH, Study Director, Affiliation: Family Health International

Overall contact:
Lut Van Damme, MD, MS, PhD, Phone: (703) 516-9779, Email: lvandamme@fhi.org

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.

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

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

Primary outcome:

Combined incidence of HIV-1 and HIV-2 infection as determined by detection of HIV antibodies using HIV rapid tests

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

Frequency and nature of adverse events (AEs) during and within 4 weeks after study product administration

Secondary outcome:

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

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)

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

Incidence of pregnancy loss, prematurity, low birth weight, and congenital abnormalities

Pill counts and participant report of adherence to once-daily pill taking

Participant report of the number of sexual partners and frequency of unprotected sexual acts over time

Participant report of sexual behaviors and sex partner characteristics by participants who seroconvert and matched HIV negative participants

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.

Minimum age: 18 Years. Maximum age: 35 Years. Gender(s): Female.

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 non-reactive HIV rapid test results at the screening and enrollment visits

6. 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

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 < 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)

11. Not received or receiving an experimental HIV vaccine, participating in another HIV prevention study or participating in any other clinical trial

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)

Lut Van Damme, MD, MS, PhD, Phone: (703) 516-9779, Email: lvandamme@fhi.org

Arusha Clinic, Levolosi Health Center, Arusha, Tanzania

Research, Training & Care Center - Kamuzu Central Hospital, Lilongwe, Central Region, Malawi

Setshaba Research Centre, Pretoria, Gauteng, South Africa

Bondo Clinic, Bondo District Hospital, Bondo, Nyanza, Kenya

University of Malawi College of Medicine - Johns Hopkins University, Blantyre, Southern Region, Malawi

University of Cape Town, Cape Town, Western Cape, South Africa

Starting date: February 2009
Ending date: February 2013
Last updated: October 13, 2008