HIV PreventionPhase 3NCT01386294
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
A Phase 3 study testing Tenofovir gel in people with HIV Prevention, run by CONRAD at 9 sites in South Africa.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- HIV Prevention
- What is being tested?
- Tenofovir gel
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2,059 participants
- Where
- 9 sitesSouth Africa
- Study dates
- Oct 2011to Aug 2014
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Show all 18Show fewer
- 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
- Drugs that slow renal excretion
- Immune system modulators
- Other antiretrovirals
Who cannot join
- 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.
Show all 16Show fewer
- 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)
- Has a clinically apparent finding on speculum pelvic examination (observed by study staff) involving deep epithelial disruption. Otherwise eligible participants with speculum pelvic examination findings involving deep epithelial disruption may proceed with enrolment after the findings have resolved and the inclusion/exclusion are met.
- 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.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
South Africa9 sites
Desmond Tutu HIV Centre / University of Cape Town
Cape Town
Perinatal HIV Research Unit / University of the Witwatersrand
Diepkloof
Wits Reproductive Health and HIV Institute / University of the Witwatersrand
Hillbrow
Qhakaza Mbokodo Research Clinic
Ladysmith, 3370
MatCH Edendale Research Center
Pietermaritzburg, KwaZulu-Natal, 316
Medunsa Clinical Research Unit / Ga-Ra
Pretoria
The Aurum Institute (Rustenburg)
Rustenburg
Setshaba Research Centre
Soshanguve
The Aurum Institute, Tembisa Hospital
Tembisa
About this study
Official title: A Phase III, Multi-Centre, Randomized Controlled Trial to Assess the Safety and Effectiveness of the Vaginal Microbicide 1% Tenofovir Gel in the Prevention of Human Immunodeficiency Virus Type 1 Infection in Women, and to Examine Effects of the Microbicide on the Incidence of Herpes Simplex Virus Type 2 Infection
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.
Read the detailed description
This is a phase III, multicenter trial to assess the safety and effectiveness of 1% tenofovir gel, administered vaginally by approximately 2900 sexually active women at high risk for sexually transmitted HIV. Approximately 2600 women aged 18-30 years old will be enrolled to achieve the required number of endpoints to show an effect on HIV-1 infection, while up to 300 additional women aged 31-40 years old will be enrolled to collect more safety information in this age group.
This is an event driven study that plans to randomize seronegative women. Participants will be randomized to a 1:1 ratio to receive 1% tenofovir gel or placebo gel. Each will be asked to insert a dose of the assigned study product within 12 hours prior to a coital event and another dose as soon as possible within 12 hours after a coital event. Participants will be advised to use only two doses of gel in a 24 hour period.
All women will be evaluated for the rates of adverse events and the rate of HIV seroconversion. In addition, the study will evaluate several secondary endpoints that bear directly on potential risks and benefits of vaginal tenofovir gel use.
- Conditions
- HIV Prevention
- Being tested
- Tenofovir gel, Universal placebo gel
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tenofovir gelDrug
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.
Universal placebo gelDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Universal placebo gel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 30 months
Safety
Grade 2, 3, and 4 clinical and laboratory adverse events as defined by the DAIDS toxicity table
Measured: 30 months
Secondary outcomes (4)
Incidence of HSV-2 infection
HSV-2 status will be established at enrollment according to a testing algorithm in the protocol. At product discontinuation samples of all those that were HSV-2 seronegative at enrollment will be tested. To identify and confirm incident HSV-2 infections and the timing of these infections, blood samples that were stored will be tested to determine the earliest equivocal or positive result. These samples will be then be tested by HSV Western blot. Samples positive on HSV Western blot will be deemed to be incident HSV-2 infections.
Measured: 30 months
Pregnancy
Incidence of pregnancy loss, prematurity, low birth weight, and major and minor congenital anomalies will be determined
Measured: 30 months
Gel and condom use
Measured: 30 months
HIV-1 incidence after product withdrawal
HIV testing will be conducted 3 months after product discontinuation and if HIV positive, the last stored sample will be tested to ascertain timing of infection and viral tenofovir resistance testing will be performed
Measured: 3 months after product withdrawal
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2011 (estimated)
- Study startOct 2011
- Primary completionAug 2014
- Study completionAug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV PreventionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 2,059 participants (actual)
Sponsor and investigators
- Lead sponsor
- CONRAD
- Sponsor type
- University, hospital or other
- Collaborators
- Follow-on African Consortium for Tenofovir Studies (FACTS), United States Agency for International Development (USAID)
- Responsible party
- Sponsor
- Investigators
- Helen Rees, Prof, Study chair, University of Witwatersrand, South Africa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01386294
- Sponsor's protocol ID
- FACTS 001
- Status last verified
- Apr 2015
- First submitted
- 28 Jun 2011
- Last updated
- 17 Apr 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 30507409
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Multi-Centre, Randomized Controlled Trial to Assess the Safety and Effectiveness of the Vaginal Microbicide 1% Tenofovir Gel in the Prevention of Human Immunodeficiency Virus Type 1 Infection in Women, and to Examine Effects of the Microbicide on the Incidence of Herpes Simplex Virus Type 2 Infection
- ClinicalTrials.gov ID
- NCT01386294
- Acronym / sponsor ID
- FACTS 001
- Conditions
- HIV Prevention
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,059 participants (actual)
- Lead sponsor
- CONRADUniversity, hospital or other
- Collaborators
- Follow-on African Consortium for Tenofovir Studies (FACTS), United States Agency for International Development (USAID)
- Study start
- Oct 2011
- Primary completion
- Aug 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 1 Jul 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a phase III, multicenter trial to assess the safety and effectiveness of 1% tenofovir gel, administered vaginally by approximately 2900 sexually active women at high risk for sexually transmitted HIV. Approximately 2600 women aged 18-30 years old will be enrolled to achieve the required number of endpoints to show an effect on HIV-1 infection, while up to 300 additional women aged 31-40 years old will be enrolled to collect more safety information in this age group.
This is an event driven study that plans to randomize seronegative women. Participants will be randomized to a 1:1 ratio to receive 1% tenofovir gel or placebo gel. Each will be asked to insert a dose of the assigned study product within 12 hours prior to a coital event and another dose as soon as possible within 12 hours after a coital event. Participants will be advised to use only two doses of gel in a 24 hour period.
All women will be evaluated for the rates of adverse events and the rate of HIV seroconversion. In addition, the study will evaluate several secondary endpoints that bear directly on potential risks and benefits of vaginal tenofovir gel use.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tenofovir 1% vaginal gel | Experimental | Drug: Tenofovir gelParticipants 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. |
| Universal placebo gel | Placebo comparator | Drug: Universal placebo gelParticipants 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. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (18 listed)
- 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).
Key exclusion criteria (16 listed)
- History of adverse reaction to latex.
- Plans any of the following during the study period
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tenofovir gelTenofovir 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. | Drug | Tenofovir 1% vaginal gel |
| Universal placebo gelThe 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 | Drug | Universal placebo gel |
Primary outcome
Effectiveness
Time frame: 30 months
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
Safety
Time frame: 30 months
Grade 2, 3, and 4 clinical and laboratory adverse events as defined by the DAIDS toxicity table
4 secondary outcomes
Incidence of HSV-2 infection
Time frame: 30 months
Pregnancy
Time frame: 30 months
Gel and condom use
Time frame: 30 months
HIV-1 incidence after product withdrawal
Time frame: 3 months after product withdrawal
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2015.
- Derived from this study: PubMed 30507409Delany-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.
Related trials for HIV Prevention
Not yet recruiting
HealthMpowerment Korea: Pilot Testing the Cultural Adaptation of a Digital HIV Intervention for Men Who Have Sex With Men in South Korea
HIV Infections, HIV Prevention and Care
Not yet recruiting
HIV/STI/HCV Testing and Overdose Prevention Among Survivors of Sex Trafficking
HIV Testing, STI
Not yet recruiting
HC-HMP: Healthy Choices Implementation Trial
Alcohol Drinking, HIV Infections
Not yet recruitingPhase 4
NOTRE: Optimizing Long-Acting Pre-Exposure Prophylaxis and Medications for Opioid Use Disorder Interventions in Carceral Settings
HIV Infections, Opioid Use Disorder
Active, not recruitingPhase 3
Long-term Follow-up of Long-acting Cabotegravir (CAB LA) for PrEP (Pre-exposure Prophylaxis) in Participants at Risk of Acquiring HIV (Human Immunodeficiency Virus)
HIV Infections
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Helen Rees, Prof study chair
University of Witwatersrand, South Africa
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tenofovir gel in people with HIV Prevention, run by CONRAD at 9 sites in South Africa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effectiveness (time frame: 30 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01386294, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2015.