Clinical trial NCT01337583: A Safety and Efficacy Trial of Dapivirine Vaginal Ring in Africa
Official title: A Multi-Centre, Randomised, Double-Blind, Placebo-Controlled Phase III Safety and Efficacy Trial of a Vaginal Matrix Ring With Dapivirine for the Prevention of HIV-1 Infection in Women
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: HIV Infections
Keywords: HIV Infections
Anti-HIV agents
HIV-1
Lead sponsor: International Partnership for Microbicides, Inc.
Sponsor class: INDUSTRY
First posted: 2011-04-19
Enrollment: 0
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 III study to asses the safety and efficacy of a silicone elastomer vaginal ring containing 25mg of dapivirine.


Eligibility criteria: Inclusion Criteria:

* Women \>18 and \<40 years of age who can provide informed consent
* Available for all visits and consent to follow all procedures scheduled for the trial
* Generally healthy and self-reported sexually active (defined as an average of at least one penetrative penile vaginal coital act per month for the last 3 months prior to enrolment)
* HIV-negative as determined by the HIV algorithm applied at screening and enrolment
* On a stable form of contraception and willing to continue on stable contraception for the duration of the clinical trial;
* Asymptomatic for genital infections at the time of enrolment (if a woman is diagnosed with any clinically significant treatable STI, she must have initiated treatment at least 1 week prior to enrolment and have completed the full course of treatment)
* Willing to answer questions about adherence, sexual behaviour, vaginal practices and ring acceptability;
* Willing to provide adequate locator information for trial retention purposes and be reachable per local standard procedures (e.g., by home visit or telephone; or via family or close neighbour contacts \[confidentiality to be maintained\])
* Willing to refrain from participation in another research trial using drugs, vaccines, medical devices, microbicides or oral pre-exposure prophylaxis investigational drugs for the duration of the IPM 009B trial;
* 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;
* Willing to refrain from use of vaginal products or objects including spermicides, tampons, female condoms, cotton wool, rags, diaphragms, cervical caps (or any other vaginal barrier method), douches and drying agents within 14 days from enrolment and for the duration of the trial.

Exclusion Criteria:

* Currently pregnant or last pregnancy within 3 months prior to screening;
* Currently breast-feeding
* Participated in another research trial using drugs, medical devices, microbicides or oral pre-exposure prophylaxis agents within 60 days prior to screening
* Previously participated or currently participating in any HIV vaccine trial
* Untreated, clinically significant urogenital infections (either symptomatic or asymptomatic), e.g., urinary tract or other sexually transmitted infections, or other gynaecological symptoms within 1 week prior to enrolment
* History of significant urogenital or uterine prolapse, undiagnosed vaginal bleeding, urethral obstruction, incontinence or urge incontinence
* Any gynaecological surgery within 90 days prior to enrolment
* Any Grade 3 or 4 baseline haematology, chemistry or urinalysis laboratory value according to the DAIDS Table for Grading Adverse Experiences, or clinically significant Grade 2 findings
* Any history of anaphylaxis or severe allergy resulting in angioedema; or a history of sensitivity/allergy to latex or a silicone elastomer
* Any history of diabetes mellitus and chronic use of oral steroid therapy and any uncontrolled serious chronic or progressive disease
* Cervical cytology at screening that requires cryotherapy, biopsy, treatment (other than for infection), or further evaluation \[this includes any findings of atypical squamous cells of undetermined significance (ASCUS)\]
* Any condition(s) that, in the opinion of the investigator, might put the participant at risk, or interfere with the trial objectives, or adherence to trial requirements

Primary outcomes:
measure: Efficacy as determined by HIV-1 seroconversion rate per person-years of product use, measured at the end of the investigational product use period.
timeFrame: 15 months
measure: Safety as determined by grade 3 and 4 AE's, clinically significant grade 2 laboratory findings (based on DAIDS grading) and all serious AE's.
timeFrame: 15 months
Secondary outcomes:
measure: Adherence to the protocol-specific product regimen as determined by self-reported diary cards and questionnaires.
timeFrame: 15 months
measure: The incidence of curable STI's or pregnancy as determined by STI testing and pregnancy testing.
timeFrame: 15 months
Other outcomes:
Locations:
city: Mbita
country: Kenya
facility: Suba District Hospital
city: Lilongwe
country: Malawi
facility: University of North Carolina Project
city: Nyanga
country: South Africa
facility: Desmond Tutu HIV Foundation, Nyanga (DTHF)
state: Cape Town
city: Pinetown
country: South Africa
facility: Prevention of HIV / AIDS (PHIVA) Project
state: KwaZulu Natal
city: Plessislaer
country: South Africa
facility: Maternal, Adolescent and Child Health (MatCH)
Study officials:
affiliation: IPM
name: Annalene Nel
role: STUDY_DIRECTOR
References: