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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

16 april 2015 bijgewerkt door: CONRAD

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.

Studie Overzicht

Toestand

Voltooid

Conditie

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

2059

Fase

  • Fase 3

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

      • Cape Town, Zuid-Afrika
        • Desmond Tutu HIV Centre / University of Cape Town
      • Diepkloof, Zuid-Afrika
        • Perinatal HIV Research Unit / University of the Witwatersrand
      • Hillbrow, Zuid-Afrika
        • Wits Reproductive Health and HIV Institute / University of the Witwatersrand
      • Ladysmith, Zuid-Afrika, 3370
        • Qhakaza Mbokodo Research Clinic
      • Pretoria, Zuid-Afrika
        • Medunsa Clinical Research Unit / Ga-Ra
      • Rustenburg, Zuid-Afrika
        • The Aurum Institute (Rustenburg)
      • Soshanguve, Zuid-Afrika
        • Setshaba Research Centre
      • Tembisa, Zuid-Afrika
        • The Aurum Institute, Tembisa Hospital
    • Kwa-Zulu NAtal
      • Pietermaritzburg, Kwa-Zulu NAtal, Zuid-Afrika, 316
        • MatCH Edendale Research Center

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar tot 40 jaar (Volwassen)

Accepteert gezonde vrijwilligers

Ja

Geslachten die in aanmerking komen voor studie

Vrouw

Beschrijving

Inclusion Criteria:

  • 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
    • Drugs that slow renal excretion
    • Immune system modulators
    • Other antiretrovirals

Exclusion Criteria:

  • 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)
  • 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.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Preventie
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Verviervoudigen

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Tenofovir 1% vaginal gel
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.
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.
Placebo-vergelijker: Universal placebo gel
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.
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

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Effectiveness
Tijdsspanne: 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
30 months
Safety
Tijdsspanne: 30 months
Grade 2, 3, and 4 clinical and laboratory adverse events as defined by the DAIDS toxicity table
30 months

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Incidence of HSV-2 infection
Tijdsspanne: 30 months
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.
30 months
Pregnancy
Tijdsspanne: 30 months
Incidence of pregnancy loss, prematurity, low birth weight, and major and minor congenital anomalies will be determined
30 months
Gel and condom use
Tijdsspanne: 30 months
30 months
HIV-1 incidence after product withdrawal
Tijdsspanne: 3 months 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
3 months after product withdrawal

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Onderzoekers

  • Studie stoel: Helen Rees, Prof, University of Witwatersrand, South Africa

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 oktober 2011

Primaire voltooiing (Werkelijk)

1 augustus 2014

Studie voltooiing (Werkelijk)

1 augustus 2014

Studieregistratiedata

Eerst ingediend

28 juni 2011

Eerst ingediend dat voldeed aan de QC-criteria

29 juni 2011

Eerst geplaatst (Schatting)

1 juli 2011

Updates van studierecords

Laatste update geplaatst (Schatting)

17 april 2015

Laatste update ingediend die voldeed aan QC-criteria

16 april 2015

Laatst geverifieerd

1 april 2015

Meer informatie

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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