Safety and Effectiveness of Tenofovir Gel in the Prevention of Human Immunodeficiency Virus (HIV-1) Infection in Women and the Effects of Tenofovir Gel on the Incidence of Herpes Simplex Virus (HSV-2) Infection

NCT01386294 | Completed Phase 3 DMC

• 1 other identifier: FACTS 001
• Study Type: interventional
• Target: 2,059
• Locations: 1 country
• Sites: 9

Brief Summary

The purpose of the study is to assess the safety and effectiveness of intravaginal 1% tenofovir gel in preventing Human Immunodeficiency Virus (HIV-1) infection and Herpes Simplex Virus (HSV-2) infection in sexually active women.

Conditions

HIV Prevention

Outcome Measures

Primary Outcomes (2)

• Effectiveness

  Incidence of HIV-1 infection: HIV incidence will be determine by detection of HIV antibodies using two HIV rapid tests (of which one will be FDA approved) according to algorithm in protocol. One of the rapid tests will detect both HIV-1 and HIV-2; the other will be specific for HIV-1. All endpoints will be reviewed by an expert committee (the Endpoint Adjudication Committee). In carrying out this review, the Committee will use guidelines prepared by the protocol committee for this purpose and recorded in the Manual of Procedures

  30 months

• Safety

  Grade 2, 3, and 4 clinical and laboratory adverse events as defined by the DAIDS toxicity table

  30 months

Secondary Outcomes (4)

• Incidence of HSV-2 infection

  30 months

• Pregnancy

  30 months

• Gel and condom use

  30 months

• HIV-1 incidence after product withdrawal

  3 months after product withdrawal

Study Arms (2)

Tenofovir 1% vaginal gel

EXPERIMENTAL

Participants will be required to insert a single dose of assigned gel intravaginally up to 12 hours before coitus and a second dose within 12 hours after coitus but no more than 2 applications within a 24 hour period.

Drug: Tenofovir gel

Universal placebo gel

PLACEBO COMPARATOR

Participants will be required to insert a single dose of assigned gel intravaginally up to 12 hours before coitus and a second dose within 12 hours after coitus but no more than 2 applications within a 24 hour period.

Drug: Universal placebo gel

Interventions

Tenofovir gel DRUG

Tenofovir gel is a clear, transparent, viscous gel at concentrations of 1% formulated in purified water with edentate disodium, citric acid, glycerin, methylparaben, propylparaben, HEC, and pH adjusted to 4-5. Tenofovir gel will be supplies in a 4 ml single use applicator containing approximately 4 grams of gel, equivalent to approximately 40mg of tenofovir.

Tenofovir 1% vaginal gel

Universal placebo gel DRUG

The placebo gel is an inert gel containing HEC as the gelling agent, purified water, sodium chloride, sorbic acid and sodium hydroxide. Each applicator contains approximately 4ml of placebo gel

Universal placebo gel

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Confirmed age 18-40 years (inclusive)
• Able and willing to provide written informed consent
• Able and willing to provide adequate locator information for study retention and safety purposes
• Sexually active, defined as having had vaginal intercourse at least twice in the past 30 days prior to screening
• HIV negative on two rapid tests performed by study staff within 30 days of enrolment (see algorithm in Appendix 3).
• No evidence of glycosuria
• No evidence of proteinuria greater than trace\*
• No history of pathological bone fractures
• Have a negative pregnancy test
• Women currently breastfeeding may be enrolled in the study
• Agree to use a study-approved effective non-barrier form of contraception
• Agree to adhere to study visits and procedures
• Willing to use study gel as advised
• Not using or taking any of the following groups of medications:
• Nephrotoxic agents

You may not qualify if:

• History of adverse reaction to latex.
• Plans any of the following during the study period
• To travel away from the study site for more than 30 consecutive days.
• To relocate away from the study site.
• To become pregnant.
• To enrol in any other study of an investigational product or behaviour modification related to HIV prevention.
• If in the opinion of the examining clinician, is not sexually active
• Inadequate renal function (serum creatinine greater than 1.5mg/dl and creatinine clearance less than 50ml/min, as estimated using the method of Cockcroft and Gault96 )
• Grade 3 and above ALT and AST at screening or any clinical sign of liver disease ( e.g. ascites, hepatomegaly, jaundice)
• Abnormal serum phosphate levels (Grade 3 and above)
• Received previously or receiving an experimental HIV vaccine
• Currently participating in another HIV prevention intervention study or participation in any other clinical trial with a biomedical intervention in the last six months
• Has current STI symptoms and/or other reproductive tract infection requiring treatment, as assessed by study staff. Otherwise eligible participants diagnosed during screening with infection(s) requiring treatment may be enrolled provided that treatment has been completed.
• Any clinical evidence of untreated cervical abnormalities
• Has any other condition that, based on the opinion of the Investigator or designee, would preclude provision of informed consent, make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.

Sponsors & Collaborators

• CONRAD: lead
• Follow-on African Consortium for Tenofovir Studies (FACTS): collaborator
• United States Agency for International Development (USAID): collaborator

Study Sites (9)

MatCH Edendale Research Center

Pietermaritzburg, KwaZulu-Natal, 316, South Africa

Location

Desmond Tutu HIV Centre / University of Cape Town

Cape Town, South Africa

Location

Perinatal HIV Research Unit / University of the Witwatersrand

Diepkloof, South Africa

Location

Wits Reproductive Health and HIV Institute / University of the Witwatersrand

Hillbrow, South Africa

Location

Qhakaza Mbokodo Research Clinic

Ladysmith, 3370, South Africa

Location

Medunsa Clinical Research Unit / Ga-Ra

Pretoria, South Africa

Location

The Aurum Institute (Rustenburg)

Rustenburg, South Africa

Location

Setshaba Research Centre

Soshanguve, South Africa

Location

The Aurum Institute, Tembisa Hospital

Tembisa, South Africa

Location

Related Publications (1)

• Delany-Moretlwe S, Lombard C, Baron D, Bekker LG, Nkala B, Ahmed K, Sebe M, Brumskine W, Nchabeleng M, Palanee-Philips T, Ntshangase J, Sibiya S, Smith E, Panchia R, Myer L, Schwartz JL, Marzinke M, Morris L, Brown ER, Doncel GF, Gray G, Rees H. Tenofovir 1% vaginal gel for prevention of HIV-1 infection in women in South Africa (FACTS-001): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2018 Nov;18(11):1241-1250. doi: 10.1016/S1473-3099(18)30428-6. Epub 2018 Oct 24.

  PMID: 30507409 DERIVED

Study Officials

• Helen Rees, Prof

  University of Witwatersrand, South Africa

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2011
• First Posted: July 1, 2011
• Study Start: October 1, 2011
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: April 17, 2015

Record last verified: 2015-04

Locations

ZA (9)