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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00441298
• Other study ID #: CAPRISA 004
• Secondary ID: PHSC study #9946
• Status: Completed
• Phase: Phase 2
• First received: February 27, 2007
• Last updated: January 29, 2016
• Start date: May 2007
• Est. completion date: March 2010

Study information

• Verified date: January 2016
• Source: Centre for the AIDS Programme of Research in South Africa
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Africa: Medicines Control Council
• Study type: Interventional

Clinical Trial Summary

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.

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

• CAPRISA eThekwini Clinical Research Site, Durban, South Africa

Recruitment information / eligibility

• Status: Completed
• Enrollment: 889
• Est. completion date: March 2010
• Est. primary completion date: December 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections

Intervention

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.
• 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.

Locations

Country	Name	City	State
South Africa	CAPRISA eThekwini Clinical Research Site	Durban	KwaZulu-Natal
South Africa	CAPRISA, Vulindlela Clinical Research Site	Pietermaritzburg	KwaZulu-Natal

Sponsors (4)

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

Country where clinical trial is conducted

South Africa, 

References & Publications (2)

Abdool Karim Q, Abdool Karim SS, Frohlich JA, Grobler AC, Baxter C, Mansoor LE, Kharsany AB, Sibeko S, Mlisana KP, Omar Z, Gengiah TN, Maarschalk S, Arulappan N, Mlotshwa M, Morris L, Taylor D; CAPRISA 004 Trial Group. Effectiveness and safety of tenofovi — View Citation

Mayer KH, Maslankowski LA, Gai F, El-Sadr WM, Justman J, Kwiecien A, Mâsse B, Eshleman SH, Hendrix C, Morrow K, Rooney JF, Soto-Torres L; HPTN 050 Protocol Team. Safety and tolerability of tenofovir vaginal gel in abstinent and sexually active HIV-infected and uninfected women. AIDS. 2006 Feb 28;20(4):543-51. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	To assess tenofovir resistance in HIV seroconvertors in the trial		performed at the post-seroconversion visit	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	No

External Links

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