Clinical trial NCT01539226: Safety and Efficacy Trial of a Dapivirine Vaginal Matrix Ring in Healthy HIV-Negative Women
Official title: A Multi-Centre, Randomised, Double-Blind, Placebo-Controlled Safety and Efficacy Trial of a Dapivirine Vaginal Matrix Ring in Healthy HIV-Negative Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infections
Keywords: HIV Infections
Anti-HIV agents
HIV-1
Lead sponsor: International Partnership for Microbicides, Inc.
Sponsor class: INDUSTRY
First posted: 2012-02-27
Enrollment: 1959
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This is a double-blind, randomised, placebo-controlled study to assess the safety and efficacy of a silicone elastomer vaginal matrix ring.

Detailed description: A multi center, randomized, double-blind, placebo=controlled safety and efficacy trial of a Dapivirine Vaginal Matrix Ring in healthy HIV-negative women.

Eligibility criteria: Inclusion Criteria:

* Women \> 18 and \< 45 years of age, at screening, who can provide informed consent;
* Available for all visits and consent to follow all procedures scheduled for the trial;
* 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 screening);
* HIV-negative as determined by the HIV algorithm applied at screening and enrolment;
* On a stable form of contraception as defined within section 5.4 and willing to continue on stable contraception for the duration of the clinical trial, unless post-menopausal or surgically sterilised;
* Asymptomatic for genital infections at the time of enrolment (if a woman is diagnosed with any clinically significant curable STI, she must have initiated treatment at least 1 week prior to enrolment and have completed the full course of treatment);
* 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 027 trial.

Exclusion Criteria:

* Currently pregnant or last pregnancy within 3 months prior to screening or intends to become pregnant during trial participation;
* Currently breast-feeding;
* Non-therapeutic injection drug use in the 12 months prior to screening;
* 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 , e.g., urinary tract, or other sexually transmitted infections, or other gynaecological symptoms within 1 week prior to enrolment;
* Has a Grade 2 or higher pelvic examination finding, according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events; Addendum 1 Female Genital Grading Table for Use in Microbicide Studies;
* History of significant urogenital or uterine prolapse, undiagnosed vaginal bleeding, diagnosed chronic and/or recurrent vulvovaginal candidiasis, urethral obstruction, incontinence or urge incontinence;
* Any gynaecological surgery within 90 days prior to screening;
* Any Grade 1 or higher baseline aspartate aminotransferase (AST), alanine transaminase (ALT), or platelet count, and any Grade 2 or higher baseline haematology, chemistry or urinalysis laboratory value according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events;
* 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 corticosteroid therapy; and any uncontrolled serious chronic or progressive disease;
* Cervical cytology at screening that requires cryotherapy, biopsy or treatment (other than for infection). Women with Grade 1 cervical cytology findings can be enrolled upon completion of the initial phase of evaluation if no current treatment is indicated (based on local standard of care for management of abnormal cervical cytology);
* Any condition(s) that, in the opinion of the investigator, might put the participant at risk, or interfere with the trial objectives or the participant's adherence to trial requirements.

Primary outcomes:
measure: HIV-1 Seroconversion According to Comprehensive HIV Testing Algorithm.
timeFrame: 24 months
measure: All Adverse Events
timeFrame: 24 months
Secondary outcomes:
measure: The Incidence Rate of HIV-2 Seroconversion.
timeFrame: 24 months
measure: The Incidence of Curable STIs
timeFrame: 24 months
measure: Percentage of Participants With Pregnancy in Each Trial Arm Over the IP Use Period;
timeFrame: 24 months
measure: The Percentage of Women Who Report Adherence to the Use of the Vaginal Ring Inserted Once Every 4 Weeks Over the Trial Period;
timeFrame: 24 months
measure: The Percentage of Women Who Report the Use of the Vaginal Ring as Acceptable;
timeFrame: 24 months
measure: The Percentage of Participants With HIV-1 Drug Resistance Mutations Among Participants Who Acquire HIV-1.
timeFrame: 24 months
Other outcomes:
Locations:
city: Ladysmith
country: South Africa
facility: Qhakaza Mbokodo
state: Kwazulu Natal
city: Pinetown
country: South Africa
facility: Prevention of HIV / AIDS (PHIVA) Project
state: KwaZulu Natal
city: Elandsdoorn
country: South Africa
facility: Ndlovu Medical Centre
state: Limpopo
city: Brits
country: South Africa
facility: Madibeng Centre for Research (MCR)
city: Cape Town
country: South Africa
facility: Desmond Tutu HIV Foundation, Guinea Fowl Road, Sunnydale, Fish Hoek
city: Plessislaer
country: South Africa
facility: Maternal, Adolescent and Child Health (MatCH)
city: Masaka
country: Uganda
facility: MRC/UVRI Uganda Research Unit on AIDS, Plot 51-59, Nakiwogo Road, PO BOX 49
Study officials:
affiliation: IPM
name: Annalene Nel
role: STUDY_DIRECTOR
References:
citation: Kusemererwa S, Abaasa A, Kabarambi A, Onyango M, Mugisha JO. Assessment of risk compensation following use of the dapivirine vaginal ring in southwestern Uganda. Sex Transm Infect. 2022 Feb;98(1):32-37. doi: 10.1136/sextrans-2020-054718. Epub 2021 Feb 4.
citation: Kusemererwa S, Abaasa A, Onyango M, Nel AM, Isaacs M, Asiki G. Contraceptive Preference Among Women at Risk of HIV Acquisition in a Preparatory Screening Study for a Phase III Microbicide Trial in South Western Uganda. AIDS Behav. 2018 Jul;22(Suppl 1):131-138. doi: 10.1007/s10461-018-2177-3.
citation: Nel A, van Niekerk N, Kapiga S, Bekker LG, Gama C, Gill K, Kamali A, Kotze P, Louw C, Mabude Z, Miti N, Kusemererwa S, Tempelman H, Carstens H, Devlin B, Isaacs M, Malherbe M, Mans W, Nuttall J, Russell M, Ntshele S, Smit M, Solai L, Spence P, Steytler J, Windle K, Borremans M, Resseler S, Van Roey J, Parys W, Vangeneugden T, Van Baelen B, Rosenberg Z; Ring Study Team. Safety and Efficacy of a Dapivirine Vaginal Ring for HIV Prevention in Women. N Engl J Med. 2016 Dec 1;375(22):2133-2143. doi: 10.1056/NEJMoa1602046.