Safety and Effectiveness of TFV 1% Gel, TDF Tablets, and FTC/TDF Tablets in Preventing HIV in Women

HIV Infections Clinical Trial

Official title:

Phase 2B Safety and Effectiveness Study of Tenofovir 1% Gel, Tenofovir Disproxil Fumarate Tablet and Emtricitabine/Tenofovir Disoproxil Fumarate Tablet for the Prevention of HIV Infection in Women

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00705679
• Other study ID #: MTN-003 (VOICE)
• Secondary ID: 10622MTN-0035U01
• Status: Completed
• Phase: Phase 2
• Start date: August 2009
• Est. completion date: August 2012

Study information

• Verified date: February 2016
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A new approach to HIV prevention currently being studied includes the use of microbicides, substances that kill microbes. Tenofovir disoproxil fumarate (TDF) and emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) are oral, FDA-approved, anti-HIV drugs, and tenofovir gel is an experimental microbicide. The purpose of this study is to determine the safety and effectiveness of daily tenofovir 1% gel compared to a vaginal placebo gel, and the safety and effectiveness of oral TDF and oral FTC/TDF compared to an oral placebo in preventing HIV infection among women at risk for sexually transmitted infections.

Description:

It is necessary to monitor both the adherence and blood levels of microbicides in order to gauge its efficacy in a study population. Utilizing an experimental microbicide (tenofovir gel) and anti-HIV drugs (TDF, FTC/TDF), this study will measure the effectiveness and safety to and blood levels of the three interventions in three regimens given to HIV uninfected women.

The expected duration of participation for each participant ranges from a minimum of 12 months to a maximum of 38 months. Study participants will be randomly assigned into one of five study groups, each with a different regimen. Group 1 participants will take one TDF tablet daily and one FTC/TDF placebo tablet daily. Group 2 participants will take one TDF placebo tablet daily and one FTC/TDF tablet daily. Group 3 participants will take one TDF placebo tablet daily and one FTC/TDF placebo tablet daily. Group 4 participants will apply tenofovir 1% gel vaginally once daily. Group 5 participants will apply tenofovir 1% placebo gel vaginally once daily.

Study visits will occur every 28 days after enrollment. Medical history, a physical exam, behavioral and adherence assessment, urine and blood collection, and counseling will occur at all visits. Blood will also be collected and archived for future research at select visits. Pharmacokinetic studies will occur at some visits. A pap smear will occur at select visits. Some participants may have hair samples collected on an optional basis at study visits every 2 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5029
• Est. completion date: August 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Willing to provide adequate locator information

• Sexually active, defined as having vaginal intercourse at least once in the 3 months prior to screening

• Agree to not participate in other research studies involving drugs, medical devices, or vaginal products for duration of study.

• Agree to use effective method of contraception. More information on this criterion can be found in the protocol.

Exclusion Criteria:

• HIV infected

• Known adverse reaction to any of the study products

• Known adverse reaction to latex

• Pathologic bone fracture not related to trauma

• Non-therapeutic injection drug use in the 12 months prior to screening

• Post-exposure prophylaxis for HIV exposure within 6 months prior to enrollment

• Last pregnancy outcome 42 days or less prior to enrollment

• Gynecologic or genital procedure 42 days or less prior to enrollment

• Participation in any other research study involving drugs, medical devices, or vaginal products 30 days or less prior to enrollment

• Currently using spermicide, interferon or interleukin therapy, or certain medications. More information on this criterion can be found in the protocol.

• Any significant uncontrolled active or chronic disease. More information on this criterion can be found in the protocol.

• Certain abnormal laboratory values. More information on this criterion can be found in the protocol.

• Intends to become pregnant in the 24 months after enrollment

• Plans to relocate or travel away from the study site for more than 8 consecutive weeks in the 24 months after enrollment

• Urinary tract infection

• Pelvic inflammatory disease, an STI, or reproductive tract infection requiring treatment

• Grade 2 or higher pelvic exam finding

• Any condition that, in the opinion of the investigator, would interfere with the study

• Pregnant or breastfeeding

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Infections

Intervention

Drug:
• Emtricitabine/tenofovir disoproxil fumarate
200 mg/300 mg tablet
• Emtricitabine/tenofovir disoproxil fumarate placebo
placebo tablet
• Tenofovir disoproxil fumarate
300 mg tablet
• Tenofovir disoproxil fumarate placebo
placebo tablet
• Tenofovir 1% vaginal gel
1 gm/100 ml of 1% gel
• Tenofovir placebo
placebo gel

Locations

Country	Name	City	State
South Africa	Overport CRS	Asherville	KwaZulu-Natal
South Africa	Chatsworth CRS	Chatsworth	KwaZulu-Natal
South Africa	eThekwini CRS	Durban	KwaZulu-Natal
South Africa	Soweto MTN CRS	Johannesburg	Gauteng
South Africa	Wits Reproductive Health and HIV Institute CRS (WRHI CRS)	Johannesburg	Gauteng
South Africa	CAPRISA Aurum CRS	Klerksdorp
South Africa	Tongaat CRS	Tongaat	KwaZulu-Natal
South Africa	Umkomaas CRS	Umkomaas	KwaZulu-Natal
South Africa	Verulam CRS	Verulam	KwaZulu-Natal
South Africa	Botha's Hill CRS	Westville	KwaZulu-Natal
South Africa	Isipingo CRS	Westville	KwaZulu-Natal
Uganda	MU-JHU Research Collaboration CRS	Kampala
Zimbabwe	Seke South CRS	Chitungwiza
Zimbabwe	Zengeza CRS	Chitungwiza
Zimbabwe	Spilhaus CRS	Harare

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Microbicide Trials Network

Countries where clinical trial is conducted

South Africa,  Uganda,  Zimbabwe, 

References & Publications (2)

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

Rosen RK, Morrow KM, Carballo-Diéguez A, Mantell JE, Hoffman S, Gai F, Maslankowski L, El-Sadr WM, Mayer KH. Acceptability of tenofovir gel as a vaginal microbicide among women in a phase I trial: a mixed-methods study. J Womens Health (Larchmt). 2008 Apr;17(3):383-92. doi: 10.1089/jwh.2006.0325. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Person-years of Follow-up of Tenofovir 1% Gel and Vaginal Placebo Gel Arms	Participants were followed for up to 30 months. Person-years measures the amount of time for each participant, in years, from the date of enrollment to the date of the first HIV-positive test result if HIV-infected during follow-up or to the date of the last HIV-negative test result on follow-up if not HIV-infected during follow-up.	For up to 30 months of follow-up
Primary	Number of HIV-1 Infections of Tenofovir 1% Gel and Vaginal Placebo Gel Arms	Participants were followed for up to 30 months. Participants were tested monthly for HIV-1 and positive rapid test results were confirmed by means of an enzyme-linked immunosorbent assay (EIA) and subsequent Western blotting (WB).	For up to 30 months of follow-up
Primary	Incidence Rate of HIV-1 Infections of Tenofovir 1% Gel and Vaginal Placebo Gel Arms	This is the number of HIV-1 infections divided by the amount of person-years of follow-up time to HIV-1 infection status, multiplied by 100 (per 100 person-years).	For up to 30 months of follow-up
Primary	Person-years of Follow-up of Oral TDF and Oral Placebo Arms	Participants were followed for up to 30 months. Person-years measures the amount of time for each participant, in years, from the date of enrollment to the date of the first HIV-positive test result if HIV-infected during follow-up or to the date of the last HIV-negative test result on follow-up if not HIV-infected during follow-up. Note that the data for both of these arms were censored on the date when sites were asked to discontinue treatment in the oral TDF group.	For up to 30 months of follow-up
Primary	Number of HIV-1 Infections of Oral TDF and Oral Placebo Arms	Participants were followed for up to 30 months. Participants were tested monthly for HIV-1 and positive rapid test results were confirmed by means of an enzyme-linked immunosorbent assay (EIA) and subsequent Western blotting (WB).	For up to 30 months of follow-up
Primary	Incidence Rate of HIV-1 Infections of Oral TDF and Oral Placebo Arms	This is the number of HIV-1 infections divided by the amount of person-years of follow-up time to HIV-1 infection status, multiplied by 100 (per 100 person-years).	For up to 30 months of follow-up
Primary	Person-years of Follow-up of Oral TDF-FTC and Oral Placebo Arms	Participants were followed for up to 30 months. Person-years measures the amount of time for each participant, in years, from the date of enrollment to the date of the first HIV-positive test result if HIV-infected during follow-up or to the date of the last HIV-negative test result on follow-up if not HIV-infected during follow-up.	For up to 30 months of follow-up
Primary	Number of HIV-1 Infections of Oral TDF-FTC and Oral Placebo Arms	Participants were followed for up to 30 months. Participants were tested monthly for HIV-1 and positive rapid test results were confirmed by means of an enzyme-linked immunosorbent assay (EIA) and subsequent Western blotting (WB).	For up to 30 months of follow-up
Primary	Incidence Rate of HIV-1 Infections of Oral TDF-FTC and Oral Placebo Arms	This is the number of HIV-1 infections divided by the amount of person-years of follow-up time to HIV-1 infection status, multiplied by 100 (per 100 person-years).	For up to 30 months of follow-up
Primary	Extended Safety of Daily Tenofovir 1% Gel, Oral TDF, and Oral FTC/TDF in Women at Risk for Sexually Transmitted HIV Infection Based on Occurrence of Grade 2, 3, and 4 Adverse Events	This measure describes the number of participants with elevated serum creatinine levels, the only safety outcome of concern where a significant difference was detected between an active arm and the corresponding placebo arm.	Throughout study, up to 2.5 years
Secondary	Frequency of HIV-1 Drug Resistance in Women Who Acquire HIV-1 Infection While Using Study Product	The primary resistance mutations for the study were pre-defined as K65R and K70E (which confer resistance to TDF), and M184I and M184V (which confer resistance to FTC), for their potential to cause a decrease in susceptibility to the study drug. K65R, K70E, and M184I were not detected in HIV-1 from any HIV-1 seroconverters while on study product. The number of HIV-1 seroconverters while on study with the M184V resistance mutation are reported for this outcome measure.	Throughout study, up to 2.5 years

External Links

•   Click here for the Microbicide Trials Network Web site
•   Haga clic aquí para ver información sobre este ensayo clínico en español