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

Study Overview
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Brief Summary
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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.

Detailed Description
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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 CAPRISA eThekwini Clinical Research Site, Durban, South Africa

Official Title
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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

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Tenofovir gel
* Drug: Placebo (Universal HEC placebo)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Tenofovir gel (a reverse transcriptase inhibitor) | Drug: Tenofovir gel<br>* 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.<br>* Other names: Tenofovir = Viread;|
| Placebo Comparator: 2<br>Universal HEC placebo | Drug: Placebo (Universal HEC placebo)<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HIV status compared between arms (tenofovir vs placebo) | 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 | Baseline and monthly HIV testing for the duration of the study, an expected average of 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in incidence rate of deep epithelial disruption compared between arms | To assess the impact, if any, of tenofovir gel on the incidence rate of deep epithelial disruption | Baseline and monthly assessments for the duration of the study, an expected average of 18 months | 
| To assess the impact of tenofovir gel on viral load | To assess the impact, if any, of tenofovir gel on viral load in women who become infected with HIV during the trial. | measured at the first visit post HIV infection, and again 3 months later | 
| To assess tenofovir resistance in HIV seroconvertors in the trial |  | performed at the post-seroconversion visit | 
| To ascertain the impact, if any, of tenofovir gel on pregnancy rates and outcomes |  | 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 | Assess new HIV seroconversions in the period between study exit and the post study visit (range 2 to 4 months) | Assessed at post study visit | 
| Impact of tenofovir gel on other sexually transmitted infections | 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 | Change from baseline to study exit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, microbicides, safety, effectiveness, Tenofovir gel, young women, HIV Seronegativity