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

Primary Purpose

HIV Infections

Status

Completed

Phase

Phase 2

Locations

South Africa

Study Type

Interventional

Intervention

Tenofovir gel

Placebo (Universal HEC placebo)

About this trial

This is an interventional prevention trial for HIV Infections focused on measuring microbicides, safety, effectiveness, Tenofovir gel, HIV, young women, HIV Seronegativity

Eligibility Criteria

18 Years - 40 Years (Adult)FemaleAccepts Healthy Volunteers

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.

Sites / Locations

CAPRISA eThekwini Clinical Research Site
CAPRISA, Vulindlela Clinical Research Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm Description

Tenofovir gel (a reverse transcriptase inhibitor)

Universal HEC placebo

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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.

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

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

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

Full Information

NCT ID

NCT00441298

First Posted

February 27, 2007

Last Updated

January 29, 2016

Sponsor

Centre for the AIDS Programme of Research in South Africa

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT00441298

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2016

Overall Recruitment Status

Completed

Study Start Date

May 2007 (undefined)

Primary Completion Date

December 2009 (Actual)

Study Completion Date

March 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Centre for the AIDS Programme of Research in South Africa

Collaborators

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

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV Infections

Keywords

microbicides, safety, effectiveness, Tenofovir gel, HIV, young women, HIV Seronegativity

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

889 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

Tenofovir gel (a reverse transcriptase inhibitor)

Arm Title

Arm Type

Placebo Comparator

Arm Description

Universal HEC placebo

Intervention Type

Drug

Intervention Name(s)

Tenofovir gel

Other Intervention Name(s)

Tenofovir = Viread

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Placebo (Universal HEC placebo)

Intervention Description

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.

Primary Outcome Measure Information:

Title

Change in HIV status compared between arms (tenofovir vs placebo)

Description

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

Time Frame

Baseline and monthly HIV testing for the duration of the study, an expected average of 18 months

Secondary Outcome Measure Information:

Title

Change in incidence rate of deep epithelial disruption compared between arms

Description

To assess the impact, if any, of tenofovir gel on the incidence rate of deep epithelial disruption

Time Frame

Baseline and monthly assessments for the duration of the study, an expected average of 18 months

Title

To assess the impact of tenofovir gel on viral load

Description

To assess the impact, if any, of tenofovir gel on viral load in women who become infected with HIV during the trial.

Time Frame

measured at the first visit post HIV infection, and again 3 months later

Title

To assess tenofovir resistance in HIV seroconvertors in the trial

Time Frame

performed at the post-seroconversion visit

Title

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

Title

To assess the impact, if any, of product hold at study exit on HIV infection and tenofovir resistance

Description

Assess new HIV seroconversions in the period between study exit and the post study visit (range 2 to 4 months)

Time Frame

Assessed at post study visit

Title

Impact of tenofovir gel on other sexually transmitted infections

Description

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

Time Frame

Change from baseline to study exit

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Salim S Abdool karim, MBChB, PhD

Organizational Affiliation

CAPRISA, University of KwaZulu-Natal

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Quarraisha Abdool Karim, PhD

Organizational Affiliation

CAPRISA, University of KwaZulu-Natal

Official's Role

Principal Investigator

Facility Information:

Facility Name

CAPRISA eThekwini Clinical Research Site

City

Durban

State/Province

KwaZulu-Natal

ZIP/Postal Code

4001

Country

South Africa

Facility Name

CAPRISA, Vulindlela Clinical Research Site

City

Pietermaritzburg

State/Province

KwaZulu-Natal

ZIP/Postal Code

4013

Country

South Africa

12. IPD Sharing Statement

Citations:

PubMed Identifier

16470118

Citation

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. doi: 10.1097/01.aids.0000210608.70762.c3.

Results Reference

background

PubMed Identifier

20643915

Citation

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. doi: 10.1126/science.1193748. Epub 2010 Jul 19. Erratum In: Science. 2011 Jul 29;333(6042):524.

Results Reference

result

PubMed Identifier

26244306

Citation

Abdool Karim SS, Abdool Karim Q, Kharsany AB, Baxter C, Grobler AC, Werner L, Kashuba A, Mansoor LE, Samsunder N, Mindel A, Gengiah TN; CAPRISA 004 Trial Group. Tenofovir Gel for the Prevention of Herpes Simplex Virus Type 2 Infection. N Engl J Med. 2015 Aug 6;373(6):530-9. doi: 10.1056/NEJMoa1410649.

Results Reference

derived

PubMed Identifier

23481666

Citation

Naranbhai V, Samsunder N, Sandler NG, Roque A, Abdool Karim Q, Ndung'u T, Carr WH, Altfeld M, Douek DC, Abdool Karim SS; CAPRISA 004 Trial Team. Neither microbial translocation nor TLR responsiveness are likely explanations for preexisting immune activation in women who subsequently acquired HIV in CAPRISA 004. J Acquir Immune Defic Syndr. 2013 Jul 1;63(3):294-8. doi: 10.1097/QAI.0b013e31828e604b.

Results Reference

derived

PubMed Identifier

23472071

Citation

Matthews LT, Sibeko S, Mansoor LE, Yende-Zuma N, Bangsberg DR, Karim QA. Women with pregnancies had lower adherence to 1% tenofovir vaginal gel as HIV preexposure prophylaxis in CAPRISA 004, a phase IIB randomized-controlled trial. PLoS One. 2013;8(3):e56400. doi: 10.1371/journal.pone.0056400. Epub 2013 Mar 5.

Results Reference

derived

PubMed Identifier

22781225

Citation

Naranbhai V, Altfeld M, Abdool Karim Q, Ndung'u T, Abdool Karim SS, Carr WH; Centre for the AIDS Programme of Research in South Africa (CAPRISA) Tenofovir gel Research for AIDS Prevention Science (TRAPS) Team. Natural killer cell function in women at high risk for HIV acquisition: insights from a microbicide trial. AIDS. 2012 Sep 10;26(14):1745-53. doi: 10.1097/QAD.0b013e328357724f.

Results Reference

derived

PubMed Identifier

21385354

Citation

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. doi: 10.1186/1745-6215-12-67.

Results Reference

derived

Links:

URL

http://www.caprisa.org

Description

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

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

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