Safety and Efficacy Trial of a Dapivirine Vaginal Matrix Ring in Healthy HIV-Negative Women

NCT ID: NCT01539226

Last Updated: 2022-10-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 1959 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-03-27
• Study Completion Date: 2016-12-13

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.

Conditions

HIV Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Placebo Vaginal Ring

Vaginal Ring containing 0.0 mg Dapivirine

Group Type: PLACEBO_COMPARATOR

Placebo Vaginal Ring

Intervention Type: COMBINATION_PRODUCT

Dapivirine Vaginal Ring containing 0.0 mg of dapivirine

Dapivirine Vaginal Ring

Vaginal Ring containing 25mg of Dapivirine

Group Type: EXPERIMENTAL

Dapivirine Vaginal Ring, 25 mg

Intervention Type: COMBINATION_PRODUCT

Dapivirine Vaginal Ring containing 25 mg of dapivirine

Interventions

Placebo Vaginal Ring

Dapivirine Vaginal Ring containing 0.0 mg of dapivirine

Intervention Type: COMBINATION_PRODUCT

Dapivirine Vaginal Ring, 25 mg

Dapivirine Vaginal Ring containing 25 mg of dapivirine

Intervention Type: COMBINATION_PRODUCT

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

International Partnership for Microbicides, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Annalene Nel

Role: STUDY_DIRECTOR

Beijing Immupeutics Medicine Technology Limited

Locations

Qhakaza Mbokodo

Ladysmith, KwaZulu-Natal, South Africa

Prevention of HIV / AIDS (PHIVA) Project

Pinetown, KwaZulu-Natal, South Africa

Ndlovu Medical Centre

Elandsdoorn, Limpopo, South Africa

Madibeng Centre for Research (MCR)

Brits, , South Africa

Desmond Tutu HIV Foundation, Guinea Fowl Road, Sunnydale, Fish Hoek

Cape Town, , South Africa

Maternal, Adolescent and Child Health (MatCH)

Plessislaer, , South Africa

MRC/UVRI Uganda Research Unit on AIDS, Plot 51-59, Nakiwogo Road, PO BOX 49

Masaka, , Uganda

Countries

South Africa; Uganda

References

Kusemererwa S, Ruzagira E, Onyango M, Kabarambi A, Abaasa A. Associations between intravaginal practices and incidence of sexually transmitted infections and bacterial vaginosis among women enrolled in the dapivirine vaginal ring trial (The Ring Study) in southwestern Uganda: a retrospective secondary analysis. BMJ Open. 2024 Apr 8;14(4):e079497. doi: 10.1136/bmjopen-2023-079497.

Reference Type: DERIVED

PMID: 38589266 (View on PubMed)

Steytler J, Craig C, van der Ryst E, Van Baelen B, Nuttall J, van Niekerk N, Mellors J, Parikh U, Wallis C; Ring Study and the DREAM Trial Study Teams. Characterization of Viruses in Phase 3 and Phase 3b Trials (the Ring Study and the Dapivirine Ring Extended Access and Monitoring Trial) of the Dapivirine Vaginal Ring for Human Immunodeficiency Virus Type 1 Infection Risk Reduction. Clin Infect Dis. 2023 Mar 21;76(6):996-1002. doi: 10.1093/cid/ciac875.

Reference Type: DERIVED

PMID: 36345569 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33542153 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29855975 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27959766 (View on PubMed)

Other Identifiers

IPM 027

Identifier Type: -

Identifier Source: org_study_id