Clinical trial NCT00917891: An Expanded Safety Study of Dapivirine Gel 4759 in Africa
Official title: A Double-blind, Randomized, Placebo-Controlled Phase I/II Study to Evaluate the Safety and Acceptability of Dapivirine Gel 4759, 0.05%, 2.5g, a Vaginal Microbicide, Conducted Using Daily Monitored Adherence in Healthy, HIV-Negative Women.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: HIV Infections
Acquired Immunodeficiency Syndrome
Keywords: HIV Infections
Acquired Immunodeficiency Syndrome
Healthy
HIV seronegativity
Lead sponsor: International Partnership for Microbicides, Inc.
Sponsor class: INDUSTRY
First posted: 2009-06-10
Enrollment: 280
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine whether dapivirine gel 4759 is safe for daily use by healthy women in Kenya, Malawi, Rwanda, South Africa and Tanzania.

Detailed description: To reduce the influence of adherence as a factor in the interpretation of efficacy results, IPM is considering using a DOT (Directly Observed Therapy) based method for vaginal microbicide gel delivery in a future Phase III study. IPM has denoted this DOT based method as Daily Monitored Adherence (DMA). IPM014A is a Phase I/II study designed: (1) to assess and compare the safety of a once daily application of Dapivirine Gel 4759, 0.05% 2.5g and a matching vehicle placebo gel; (2) to assess the acceptability of a once daily application of Dapivirine gel 4759, 0.05% 2.5g and a matching vehicle placebo gel; and (3) to assess the feasibility of utilizing the DMA method for a large-scale phase III efficacy study.

Eligibility criteria: Inclusion Criteria:

1. Women 18 to 40 years of age inclusive who can give written informed consent
2. Available for all visits and consent to follow all procedures scheduled for the study
3. Agree to daily application of gel and monitoring as per Daily Monitored Adherence (DMA) method
4. Healthy and self-reported sexually active
5. HIV-negative as determined by a HIV rapid test at time of enrollment
6. On a stable form of contraception and willing to continue on this stable method of contraception, OR, Have undergone surgical sterilisation at least 3 months prior to enrollment
7. In the absence of the use of exogenous hormone(s), have a self-reported regular menstrual cycle defined as having a minimum of 21 days and a maximum of 36 days between menses
8. Upon pelvic/speculum examination and colposcopy at the time of enrollment, the cervix and vagina appear normal as determined by the investigator
9. Asymptomatic for genital infections at the time of enrollment
10. Willing to refrain from use of vaginal products or objects within 14 days prior to enrollment and for the duration of the study
11. Willing to answer acceptability and adherence questionnaires throughout the study
12. Willing to refrain from participation in any other research study for the duration of this study
13. Willing to provide adequate locator information for study retention purposes and be reachable per local standard procedures

Exclusion Criteria:

1. Currently pregnant or last pregnancy outcome within 3 months prior to enrolment
2. Currently breast-feeding
3. Participated in any other research study within 60 days prior to screening
4. Previously participated in any HIV vaccine study
5. Untreated urogenital infections (either symptomatic or asymptomatic) within 2 weeks prior to enrollment
6. Presence of abnormal physical finding on the vulva, vaginal walls or cervix during pelvic/speculum examination and/or colposcopy
7. History of significant urogenital or uterine prolapse, undiagnosed vaginal bleeding, urethral obstruction
8. Pap smear result at screening that requires cryotherapy, biopsy, treatment (other than for infection), or further evaluation
9. Any Grade 2, 3 or 4 baseline haematology, chemistry or urinalysis laboratory abnormality according to the DAIDS Table for Grading Adverse Experiences
10. Unexplained, undiagnosed abnormal bleeding per vagina, bleeding per vagina during or following vaginal intercourse, or gynaecologic surgery within 90 days prior to enrollment
11. Any history of anaphylaxis or severe allergy resulting in angioedema; or a history of sensitivity/allergy to latex
12. Any serious acute, chronic or progressive disease
13. Any condition(s) that, in the opinion of the investigator, might interfere with adherence to study requirements or evaluation of the study objectives

Primary outcomes:
measure: Gynaecological examinations, including pelvic/speculum examination and colposcopy, and laboratory STI testing.
timeFrame: Week 0, 1, 2, 4, 6 & 10
measure: Safety laboratory tests
timeFrame: enrollment & last day of gel use
measure: Adverse event/serious adverse event reports
timeFrame: throughout study
Secondary outcomes:
measure: Questionnaires concerning acceptability and adherence to daily use of vaginal gel.
timeFrame: Week 0, 2, 6 & 10
measure: Documentation of adherence to the DMA method including the Applicator Collection Checklist, focus groups and male interviews.
timeFrame: throughout study
Other outcomes:
Locations:
city: Kisumu
country: Kenya
facility: Kenya Medical Research Institute
city: Blantyre
country: Malawi
facility: Johns Hopkins Project, College of Medicine
city: Kigali
country: Rwanda
facility: Projet Ubuzima
city: Paarl
country: South Africa
facility: Be Part Clinic, Mbekweni
state: Eastern Cape
city: Ladysmith
country: South Africa
facility: Qhakaza Mbokodo
state: KwaZulu Natal
city: Pinetown
country: South Africa
facility: Prevention for HIV and AIDS Project
state: KwaZulu Natal
city: Agincourt
country: South Africa
facility: Ndlela HIV Research and Clinical Tirals Unit
state: Mpumalanga
city: Brits
country: South Africa
facility: Madibeng Centre for Research
state: North West Province
city: Cape Town
country: South Africa
facility: Desmond Tutu HIV Foundation, Nyanga
state: Western Cape
city: Moshi
country: Tanzania
facility: Kilimanjaro Christian Medical Centre
Study officials:
affiliation: IPM
name: Dr Annalene Nel
role: STUDY_DIRECTOR
References: