Clinical trial NCT01071174: A Safety Study of Dapivirine Vaginal Ring in Africa
Official title: A Double-Blind, Randomized, Placebo-Controlled Phase I/II Study to Evaluate the Safety of an Intravaginal Matrix Ring With Dapivirine in Healthy, HIV-Negative Women.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: HIV Infections
Keywords: HIV infections
Anti-HIV agents
HIV-1
Lead sponsor: International Partnership for Microbicides, Inc.
Sponsor class: INDUSTRY
First posted: 2010-02-19
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: This is a double-blind, randomized, placebo-controlled Phase I/II study to assess the safety of a silicone elastomer vaginal ring containing 25mg dapivirine.


Eligibility criteria: Inclusion Criteria:

* Women between 18 and 40 years of age inclusive who can provide informed consent
* Available for all visits and consent to follow all procedures scheduled for the study
* Healthy and self-reported sexually active
* HIV-negative
* On a stable form of contraception and willing to continue OR have undergone surgical sterilization at least 3 months prior to enrollment
* 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 35 days between menses
* Upon pelvic/speculum examination and colposcopy at the time of enrolment, the cervix and vagina appear normal as determined by the investigator
* Asymptomatic for genital infections at the time of enrolment
* Willing to refrain from use of vaginal products or objects within 14 days from enrollment and for the duration of the study
* Willing to answer to acceptability, adherence and behavioural assessments throughout the study
* Willing to refrain from participation in any other research study for the duration of their participation
* Willing to provide adequate locator information for study retention purposes and be reachable per local standard procedures

Exclusion Criteria:

* Currently pregnant or last pregnancy within 3 months prior to enrolment
* Currently breast-feeding
* Participated in any other research study within 60 days prior to screening
* Previously participated in any HIV vaccine study
* Untreated urogenital infections within 2 weeks prior to enrolment
* Presence of any abnormal physical finding on the vulva, vaginal walls or cervix during pelvic/speculum examination and/or colposcopy
* History of significant urogenital or uterine prolapse, undiagnosed vaginal bleeding, or urethral obstruction, incontinence or urge incontinence
* Pap smear result at screening that requires cryotherapy, biopsy, treatment or further evaluation
* Any Grade 2, 3 or 4 baseline (screening) haematology, chemistry or urinalysis laboratory abnormality according to the DAIDS Table for Grading Adverse Events
* Any abnormal bleeding per vagina, bleeding per vagina during or following vaginal intercourse, or gynaecologic surgery within 90 days prior to enrolment
* Any history of anaphylaxis or severe allergy resulting in angioedema; or a history of sensitivity/allergy to latex or silicone elastomer
* Any serious acute, chronic or progressive disease
* 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: Safety as determined by the proportion of women in each arm experiencing protocol-specified events, including AEs, laboratory abnormalities, cervico-vaginal abnormalities, abnormal vaginal flora/pH during the study.
timeFrame: 16 weeks
Secondary outcomes:
measure: Acceptability of the product determined by questionnaire.
timeFrame: 16 weeks
measure: Adherence to the protocol-specific product regimen as determined by self-report and clinician observation at each study visit.
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Kisumu
country: Kenya
facility: Kenya Medical Research Institute (KEMRI)
city: Lilongwe
country: Malawi
facility: University of North Carolina Project
city: Edendale
country: South Africa
facility: Reproductive Health and HIV Research Unit (RHRU)
state: Kwazulu Natal
city: Ladysmith
country: South Africa
facility: Qhakaza Mbokodo
state: Kwazulu Natal
city: Pinetown
country: South Africa
facility: Prevention for HIV and AIDS Project (PHIVA)
state: Kwazulu Natal
city: Brits
country: South Africa
facility: Madibeng Centre for Research
state: North West
city: Cape Town
country: South Africa
facility: Desmond Tutu HIV Foundation Masiphumelele
state: Western Cape
city: Cape Town
country: South Africa
facility: Desmond Tutu HIV Foundation Nyanga
state: Western Cape
city: Paarl
country: South Africa
facility: Be Part Yoluntu Centre Mbekweni
state: Western Cape
city: Moshi
country: Tanzania
facility: Kilimanjaro Christian Medical Centre (KCMC)
Study officials:
affiliation: IPM
name: Dr Annalene Nel
role: STUDY_DIRECTOR
References:
citation: Nel A, Bekker LG, Bukusi E, Hellstrӧm E, Kotze P, Louw C, Martinson F, Masenga G, Montgomery E, Ndaba N, van der Straten A, van Niekerk N, Woodsong C. Safety, Acceptability and Adherence of Dapivirine Vaginal Ring in a Microbicide Clinical Trial Conducted in Multiple Countries in Sub-Saharan Africa. PLoS One. 2016 Mar 10;11(3):e0147743. doi: 10.1371/journal.pone.0147743. eCollection 2016.