Safety and Effectiveness Study of a Candidate Vaginal Microbicide for Prevention of HIV - Full Text View

Sponsor:	Centre for the AIDS Programme of Research in South Africa
Collaborators:	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

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 Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Double Blind (Subject, 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

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS Sexually Transmitted Diseases

Drug Information available for: Tenofovir Tenofovir Disoproxil Fumarate

U.S. FDA Resources

Further study details as provided by 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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: No ]
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.

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
CAPRISA eThekwini Clinical Research Site, Durban, South Africa

Eligibility

Ages Eligible for Study:	18 Years to 40 Years
Genders 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

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

Publications:

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 tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science. 2010 Sep 3;329(5996):1168-74. Epub 2010 Jul 19.

Mayer KH, Maslankowski LA, Gai F, El-Sadr WM, Justman J, Kwiecien A, Masse 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.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Karim QA, Kharsany AB, Frohlich JA, Baxter C, Yende N, Mansoor LE, Mlisana KP, Maarschalk S, Arulappan N, Grobler A, Sibeko S, Omar Z, Gengiah TN, Mlotshwa M, Samsunder N, Karim SS. Recruitment of high risk women for HIV prevention trials: baseline HIV prevalence and sexual behavior in the CAPRISA 004 tenofovir gel trial. Trials. 2011 Mar 7;12:67.

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 20, 2012
Health Authority:	South Africa: Medicines Control Council

Keywords provided by Centre for the AIDS Programme of Research in South Africa:

microbicides
safety
effectiveness
Tenofovir gel

HIV
young women
HIV Seronegativity

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Tenofovir

Tenofovir disoproxil
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Therapeutic Uses
Pharmacologic Actions
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-HIV Agents

ClinicalTrials.gov processed this record on May 22, 2012