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

NCT00441298 | Completed Phase 2 DMC

• 2 other identifiers: CAPRISA 004PHSC study #9946
• Study Type: interventional
• Target: 889
• Locations: 1 country
• Sites: 2

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.

Conditions

HIV Infections

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (6)

• Change in incidence rate of deep epithelial disruption compared between arms

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

• To assess the impact of tenofovir gel on viral load

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

• To assess tenofovir resistance in HIV seroconvertors in the trial

  performed at the post-seroconversion visit

• 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

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

  Assessed at post study visit

Study Arms (2)

1

EXPERIMENTAL

Tenofovir gel (a reverse transcriptase inhibitor)

Drug: Tenofovir gel

2

PLACEBO COMPARATOR

Universal HEC placebo

Drug: Placebo (Universal HEC placebo)

Interventions

Tenofovir gel 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.

Also known as: Tenofovir = Viread

1

Placebo (Universal HEC placebo) 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.

2

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Centre for the AIDS Programme of Research in South Africa: lead
• FHI 360: collaborator
• United States Agency for International Development (USAID): collaborator
• CONRAD: collaborator

Study Sites (2)

CAPRISA eThekwini Clinical Research Site

Durban, KwaZulu-Natal, 4001, South Africa

Location

CAPRISA, Vulindlela Clinical Research Site

Pietermaritzburg, KwaZulu-Natal, 4013, South Africa

Location

Related Publications (8)

• 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.

  PMID: 16470118 BACKGROUND

• 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.

  PMID: 20643915 RESULT

• 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.

  PMID: 36504254 DERIVED

• 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.

  PMID: 26244306 DERIVED

• 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.

  PMID: 23481666 DERIVED

• 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.

  PMID: 23472071 DERIVED

• 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.

  PMID: 22781225 DERIVED

• 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.

  PMID: 21385354 DERIVED

Related Links

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

MeSH Terms

Conditions

HIV Infections

Interventions

Tenofovir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Salim S Abdool karim, MBChB, PhD

  CAPRISA, University of KwaZulu-Natal

  PRINCIPAL INVESTIGATOR

• Quarraisha Abdool Karim, PhD

  CAPRISA, University of KwaZulu-Natal

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 27, 2007
• First Posted: February 28, 2007
• Study Start: May 1, 2007
• Primary Completion: December 1, 2009
• Study Completion: March 1, 2010
• Last Updated: February 1, 2016

Record last verified: 2016-01

Locations

ZA (2)