Clinical Trials

MainTitle

Safety and Effectiveness Study of a Candidate Vaginal Microbicide for Prevention of HIV

This study has been completed
Sponsor
Centre for the AIDS Programme of Research in South Africa

Collaborator
FHI 360
United States Agency for International Development (USAID)
CONRAD

Information provided by (Responsible Party)
Dr Salim S Abdool Karim, Centre for the AIDS Programme of Research in South Africa

ClinicalTrials.gov Identifier
NCT00441298

First received: February 27, 2007
Last updated: January 29, 2016
Last Verified: January 2016
History of Changes
Purpose

Purpose

This phase IIb, two-arm, double-blinded, randomised, placebo controlled trial comparing 1% Tenofovir gel with a placebo gel is an expanded safety and effectiveness trial involving 900 young women at risk of sexually transmitted HIV infection. Participants will be provided with a supply of single-use, pre-filled applicators according to their randomisation. While in the study, participants will be asked to apply a first dose of the assigned study gel within 12 hours prior to coitus and insert a second dose as soon as possible within 12 hours after coitus. All participants will receive HIV risk reduction counselling, condoms, and syndromic treatment of sexually transmitted infections, if required.

Condition Intervention Phase
HIV Infections

Drug : Tenofovir gel
Drug : Placebo (Universal HEC placebo)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: Phase IIb Trial to Assess the Safety and Effectiveness of the Vaginal Microbicide 1% Tenofovir Gel for the Prevention of HIV Infection in Women in South Africa

Further study details as provided by Dr Salim S Abdool Karim, Centre for the AIDS Programme of Research in South Africa:

Primary Outcome Measures

  • Change in HIV status compared between arms (tenofovir vs placebo) [ Time Frame: Baseline and monthly HIV testing for the duration of the study, an expected average of 18 months ]
    The effectiveness of tenofovir against HIV infection will be measured by comparing the incidence of HIV in the tenofovir arm with that in the placebo arm
Secondary Outcome Measures:
  • Change in incidence rate of deep epithelial disruption compared between arms [ Time Frame: Baseline and monthly assessments for the duration of the study, an expected average of 18 months ]
    To assess the impact, if any, of tenofovir gel on the incidence rate of deep epithelial disruption
  • To assess the impact of tenofovir gel on viral load [ Time Frame: measured at the first visit post HIV infection, and again 3 months later ]
    To assess the impact, if any, of tenofovir gel on viral load in women who become infected with HIV during the trial.
  • To assess tenofovir resistance in HIV seroconvertors in the trial [ Time Frame: performed at the post-seroconversion visit ]
  • To ascertain the impact, if any, of tenofovir gel on pregnancy rates and outcomes [ Time Frame: Assessed at baseline and monthly for the duration of the study, an expected average of 18 months ]
  • To assess the impact, if any, of product hold at study exit on HIV infection and tenofovir resistance [ Time Frame: Assessed at post study visit ]
    Assess new HIV seroconversions in the period between study exit and the post study visit (range 2 to 4 months)
  • Impact of tenofovir gel on other sexually transmitted infections [ Time Frame: Change from baseline to study exit ]
    To assess the impact, if any, of tenofovir gel in preventing sexually transmitted infections, including herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) infections

Enrollment: 889
Study Start Date: May 2007
Study Completion Date: March 2010
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: 1
Tenofovir gel (a reverse transcriptase inhibitor)
Drug: Tenofovir gel

Participants will be provided with a supply of single-use, pre-filled applicators according to their randomisation. While in the study, participants will be asked to apply a first dose of the assigned study product, 1% tenofovir gel, within 12 hours prior to coitus and insert a second dose as soon as possible within 12 hours after coitus. They will be advised to use only two doses of gel in a 24-hour period.

Other Name: Tenofovir = Viread
Placebo Comparator: 2
Universal HEC placebo
Drug: Placebo (Universal HEC placebo)

Participants will be provided with a supply of single-use, pre-filled applicators according to their randomisation. While in the study, participants will be asked to apply a first dose of the assigned study product, placebo gel, within 12 hours prior to coitus and insert a second dose as soon as possible within 12 hours after coitus. They will be advised to use only two doses of gel in a 24-hour period.

Detailed Description:

Purpose: To assess the safety and effectiveness of tenofovir gel, a candidate vaginal microbicide, in sexually active women at risk for human immunodeficiency virus (HIV) infection in South Africa.
Design: Phase IIb, two-arm, double-blind, randomised, controlled trial comparing 1% tenofovir gel with a placebo gel.
Study Population: Sexually active, HIV-uninfected women aged 18 to 40 years in South Africa
Study Size: 900 women
Treatment Regimen: Participants will be provided with a supply of single-use, pre-filled applicators according to their randomisation. While in the study, participants will be asked to apply a first dose of the assigned study product, 1% tenofovir gel or placebo gel, within 12 hours prior to coitus and insert a second dose as soon as possible within 12 hours after coitus. They will be advised to use only two doses of gel in a 24-hour period.
Study Duration: Approximately 30 months in total. Accrual will require approximately 14 months and follow-up will continue until 92 incident HIV infections are observed in the study, which is expected to occur approximately 16 months after the end of the accrual period.
Primary Objective:
To evaluate the effectiveness and safety of a candidate vaginal microbicide, tenofovir gel, when applied intravaginally by women, in preventing sexually transmitted HIV infection.

Secondary

    Objectives:
    • To assess the impact, if any, of tenofovir gel on the incidence rate of deep epithelial disruption
    • To assess the impact, if any, of tenofovir gel on viral load in women who become infected with HIV during the trial.
    • To assess tenofovir resistance in HIV seroconvertors in the trial
    • To ascertain the impact, if any, of tenofovir gel on pregnancy rates and outcomes
    • To assess the impact, if any, of product hold at study exit on HIV infection and tenofovir resistance

    Ancillary Objective

•To assess the impact, if any, of tenofovir gel in preventing sexually transmitted infections, including herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) infections.
Study sites:
  • CAPRISA Vulindlela Clinical Research Site, KwaZulu-Natal, South Africa
  • SA eThekwini Clinical Research Site, Durban, South Africa

    Eligibility

    Eligibility

    Ages Eligible for Study: 18 Years to 40 Years  
    Sexes Eligible for Study: Female  
    Accepts Healthy Volunteers: Yes  

    Criteria

    Inclusion Criteria:

    • Age 18-40 years (inclusive)
    • Able and willing to provide written informed consent to be screened for, and to enrol in, the study.
    • Able and willing to provide adequate locator information for study retention purposes.
    • Sexually active, defined as having had vaginal intercourse at least twice in the past 30 days prior to screening.
    • HIV negative on testing performed by study staff within 30 days of enrolment.
    • Have a negative pregnancy test which was performed by study staff within 21 days of enrolment
    • Agree to use a non-barrier form of contraceptive
    • Agree to adhere to study visits and procedures


    Exclusion Criteria:
    • History of adverse reaction to latex.
    • Plans any of the following during the next 16 to 30 months (depending the anticipated date of study completion):
      • 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.
    • Has a creatinine clearance <50ml/min, as estimated using the method of Cockcroft and Gault(33).
    • Has active Hepatitis B infection (since January 2009)
    • Has a clinically apparent pelvic examination finding (observed by study staff) involving deep epithelial disruption. Otherwise eligible participants with pelvic examination findings involving deep epithelial disruption may proceed with enrolment after the findings have resolved and the inclusion/exclusion are met.
    • Has in the past year participated in any research related to any vaginally applied product/s.
    • 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 commenced.
    • 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.

    contacts and locations

    Contacts and Locations

    Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

    Please refer to this study by its ClinicalTrials.gov identifier: NCT00441298

    Locations

    South Africa
    CAPRISA eThekwini Clinical Research Site
    Durban, KwaZulu-Natal, South Africa, 4001
    CAPRISA, Vulindlela Clinical Research Site
    Pietermaritzburg, KwaZulu-Natal, South Africa, 4013

    Sponsors and Collaborators

    Centre for the AIDS Programme of Research in South Africa
    FHI 360
    United States Agency for International Development (USAID)
    CONRAD

    Investigators

    Principal Investigator: Salim S Abdool karim, MBChB, PhD CAPRISA, University of KwaZulu-Natal
    Principal Investigator: Quarraisha Abdool Karim, PhD CAPRISA, University of KwaZulu-Natal
    More Information

    More Information

    Additional Information:

    Central website for the Centre for the AIDS Programme of Research in South Africa

    Responsible Party: Dr Salim S Abdool Karim, Principal Investigator, Centre for the AIDS Programme of Research in South Africa  
    ClinicalTrials.gov Identifier: NCT00441298   History of Changes  
    Other Study ID Numbers: CAPRISA 004  
      PHSC study #9946  
    Study First Received: February 27, 2007  
    Last Updated: January 29, 2016  

    Keywords provided by Dr Salim S Abdool Karim, Centre for the AIDS Programme of Research in South Africa:

    microbicides
    safety
    effectiveness
    Tenofovir gel
    HIV
    young women
    HIV Seronegativity

    Additional relevant MeSH terms:
    Infection
    HIV Infections
    Acquired Immunodeficiency Syndrome
    Tenofovir
    Anti-Infective Agents

    ClinicalTrials.gov processed this data on December 08, 2017
    This information is provided by ClinicalTrials.gov.