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

NCT ID: NCT00441298

Last Updated: 2016-02-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 889 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-05-31
• Study Completion Date: 2010-03-31

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

Conditions

HIV Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

1

Tenofovir gel (a reverse transcriptase inhibitor)

Group Type: EXPERIMENTAL

Tenofovir gel

Intervention Type: DRUG

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.

2

Universal HEC placebo

Group Type: PLACEBO_COMPARATOR

Placebo (Universal HEC placebo)

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Tenofovir = Viread

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

FHI 360

OTHER

Sponsor Role: collaborator

United States Agency for International Development (USAID)

FED

Sponsor Role: collaborator

CONRAD

OTHER

Sponsor Role: collaborator

Centre for the AIDS Programme of Research in South Africa

NETWORK

Sponsor Role: lead

Responsible Party

Dr Salim S Abdool Karim

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Salim S Abdool karim, MBChB, PhD

Role: PRINCIPAL_INVESTIGATOR

CAPRISA, University of KwaZulu-Natal

Quarraisha Abdool Karim, PhD

Role: PRINCIPAL_INVESTIGATOR

CAPRISA, University of KwaZulu-Natal

Locations

CAPRISA eThekwini Clinical Research Site

Durban, KwaZulu-Natal, South Africa

CAPRISA, Vulindlela Clinical Research Site

Pietermaritzburg, KwaZulu-Natal, South Africa

Countries

South Africa

References

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.

Reference Type: BACKGROUND

PMID: 16470118 (View on PubMed)

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.

Reference Type: RESULT

PMID: 20643915 (View on PubMed)

Wang Y, Noel-Romas L, Perner M, Knodel S, Molatlhegi R, Hoger S, Birse K, Zuend CF, McKinnon LR, Burgener AD. Non-Lactobacillus-Dominant and Polymicrobial Vaginal Microbiomes Are More Common in Younger South African Women and Predictive of Increased Risk of Human Immunodeficiency Virus Acquisition. Clin Infect Dis. 2023 Apr 17;76(8):1372-1381. doi: 10.1093/cid/ciac938.

Reference Type: DERIVED

PMID: 36504254 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26244306 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23481666 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23472071 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22781225 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 21385354 (View on PubMed)

Related Links

http://www.caprisa.org

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

Other Identifiers

PHSC study #9946

Identifier Type: -

Identifier Source: secondary_id

CAPRISA 004

Identifier Type: -

Identifier Source: org_study_id