Phase 3 Safety and Effectiveness Trial of Dapivirine Vaginal Ring for Prevention of HIV-1 in Women

NCT01617096 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: MTN-020UM1AI068633-06
• Study Type: interventional
• Target: 2,629
• Locations: 4 countries
• Sites: 7

Brief Summary

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

Conditions

HIV Infections

Keywords

HIV Infections; Anti-HIV agents; HIV-1

Outcome Measures

Primary Outcomes (2)

• Efficacy as Determined by the Proportion of Women in Each Arm With HIV-1 Seroconversion After 120 Endpoints Are Observed in the Trial.

  The primary endpoint is HIV-1 seroconversion as measured by rapid and specialised laboratory testing according to comprehensive HIV testing algorithm. Endpoint confirmation of HIV infection is by Western Blot.

  minimum of 12 months and a maximum of 14 months per participant

• The Number of Participants That Experienced Grade 2, 3, 4 and Serious Adverse Events Over the Investigational Product Used Period (25 mg Dapivirine Administered in a Silicone Elastomer Vaginal Matrix Ring (DVR), Inserted Once Every 4 Weeks).

  Participants with grade 2 adverse events, judged to be related to investigational product, grade 3 and grade 4 adverse events and all serious adverse events. DAIDS severity grades are defined as follows: Grade 1 = mild Grade 2 = moderate Grade 3 = severe Grade 4 = potentially life-threatening Grade 5 = death

  minimum of 12 months and a maximum of 14 months per participant

Secondary Outcomes (3)

• Adherence to the Dapivirine Vaginal Ring.

  12 months per participant

• Acceptability of the DVR and Placebo Vaginal Ring

  12 months per participant

• Human Immunodeficiency Virus Type 1 Drug Resistance Mutations Among Participants Who Acquired HIV-1 Infection.

  minimum of 12 months and a maximum of 14 months per participant

Study Arms (2)

Dapivirine Vaginal Ring

EXPERIMENTAL

Vaginal ring containing 25mg dapivirine

Combination Product: Dapivirine Vaginal Ring

Placebo Ring

PLACEBO COMPARATOR

Vaginal ring containing no drug substance

Combination Product: Placebo Ring

Interventions

Dapivirine Vaginal Ring COMBINATION_PRODUCT

Dosage form: vaginal ring Dosage: 25mg Frequency: monthly Duration: 12 months

Dapivirine Vaginal Ring

Placebo Ring COMBINATION_PRODUCT

Vaginal ring containing no drug substance

Placebo Ring

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18 through 45 years (inclusive) at screening, verified per site SOPs; within this range, sites may restrict the upper age limit per site SOPs, to target women at high risk of HIV infection
• Able and willing to provide written informed consent to be screened for and to take part in the study
• Able and willing to provide adequate locator information, as defined in site SOPs
• HIV-uninfected based on testing performed by study staff at screening and enrollment (per applicable algorithm in Appendix II)
• Per participant report, sexually active, defined as having vaginal intercourse at least once in the 3 months prior to screening
• Using an effective method of contraception at enrollment, and intending to use an effective method for the duration of study participation; effective methods include hormonal methods (except contraceptive ring); intrauterine device (IUD); and sterilization (of participant, as defined in site SOPs)
• At screening and enrollment, agrees not to participate in other research studies involving drugs, medical devices, vaginal products, or vaccines for the duration of study participation -- Note: Tampons may be used for the duration of the trial.

You may not qualify if:

• Per participant report at screening:
• Intends to become pregnant during study participation
• Plans to relocate away from the study site during study participation
• Plans to travel away from the study site for more than 8 consecutive weeks during study participation
• Is pregnant
• Currently breastfeeding
• Diagnosed with urinary tract infection (UTI)
• \-- Note: Otherwise eligible participants diagnosed with UTI during screening are offered treatment and may be enrolled after completing treatment and all symptoms have resolved. If treatment is completed and symptoms have resolved within 28 days of obtaining informed consent for screening, the participant may be enrolled.
• Diagnosed with pelvic inflammatory disease, an STI or reproductive tract infection (RTI) requiring treatment per current WHO guidelines
• \-- Note: Otherwise eligible participants diagnosed during screening with pelvic inflammatory disease or STI/RTI requiring treatment per WHO guidelines - other than asymptomatic BV and asymptomatic candidiasis - are offered treatment and may be enrolled after completing treatment and all symptoms have resolved. If treatment is completed and symptoms have resolved within 28 days of obtaining informed consent for screening, the participant may be enrolled. Genital warts requiring treatment also must be treated prior to enrollment. Genital warts requiring therapy are defined as those that cause undue burden or discomfort to the participant, including bulky size, unacceptable appearance, or physical discomfort.
• Has a clinically apparent Grade 2 or higher pelvic exam finding (observed by study staff) as per the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Version 1.0, December, 2004 (Clarification dated August 2009), Addendum 1-Female Genital Grading Table for Use in Microbicide Studies
• Participant report and/or clinical evidence of any of the following:
• Known adverse reaction to any of the study products (ever)
• Known adverse reaction to latex (ever)
• Chronic vaginal candidiasis

Sponsors & Collaborators

• International Partnership for Microbicides, Inc.: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (7)

College of Medicine - Johns Hopkins University Research Project

Blantyre, Malawi

Location

UNC Project

Lilongwe, Malawi

Location

CAPRISA, eThekwini Clinical Research Site

Durban, KwaZulu-Natal, South Africa

Location

Desomond Tutu HIV Center

Cape Town, South Africa

Location

Wits Reproductive Health and HIV Institute

Johannesburg, South Africa

Location

MU-JHU Care LTD, MU-JHU Research Collaboration

Kampala, Uganda

Location

UZ-Obstetrics & Gynecology Research Clinic at Spillhaus

Belgravia, Harare, Zimbabwe

Location

Related Publications (9)

• Stalter RM, Dong TQ, Hendrix CW, Palanee-Phillips T, van der Straten A, Hillier SL, Kiweewa FM, Mgodi NM, Marzinke MA, Bekker LG, Soto-Torres L, Baeten JM, Brown ER; MTN-020/ASPIRE Study Team. Assessing Per-Sex-Act HIV-1 Risk Reduction Among Women Using the Dapivirine Vaginal Ring. J Infect Dis. 2024 Apr 12;229(4):1158-1165. doi: 10.1093/infdis/jiad550.

  PMID: 38099506 DERIVED

• Browne EN, Brown ER, Palanee-Phillips T, Reddy K, Naidoo L, Jeenarain N, Nair G, Husnik MJ, Singh D, Scheckter R, Soto-Torres L, Baeten JM, van der Straten A; MTN-020/ASPIRE Study Team. Patterns of Adherence to a Dapivirine Vaginal Ring for HIV-1 Prevention Among South African Women in a Phase III Randomized Controlled Trial. J Acquir Immune Defic Syndr. 2022 Aug 1;90(4):418-424. doi: 10.1097/QAI.0000000000002990.

  PMID: 35344520 DERIVED

• Leslie J, Kiweewa F, Palanee-Phillips T, Bunge K, Mhlanga F, Kamira B, Baeten J, Katz A, Hillier S, Montgomery E; MTN-020/ASPIRE Study Team. Experiences with simultaneous use of contraception and the vaginal ring for HIV prevention in sub-Saharan Africa. BMC Womens Health. 2021 Apr 23;21(1):175. doi: 10.1186/s12905-021-01321-5.

  PMID: 33892693 DERIVED

• Mayo AJ, Browne EN, Montgomery ET, Torjesen K, Palanee-Phillips T, Jeenarain N, Seyama L, Woeber K, Harkoo I, Reddy K, Tembo T, Mutero P, Tauya T, Chitukuta M, Gati Mirembe B, Soto-Torres L, Brown ER, Baeten JM, van der Straten A; MTN-020/ASPIRE study team. Acceptability of the Dapivirine Vaginal Ring for HIV-1 Prevention and Association with Adherence in a Phase III Trial. AIDS Behav. 2021 Aug;25(8):2430-2440. doi: 10.1007/s10461-021-03205-z. Epub 2021 Mar 13.

  PMID: 33713213 DERIVED

• Palanee-Phillips T, Brown ER, Szydlo D, Matovu Kiweewa F, Pather A, Harkoo I, Nair G, Soto-Torres L, Hillier SL, Baeten JM; MTN-020/ASPIRE Study Team. Risk of HIV-1 acquisition among South African women using a variety of contraceptive methods in a prospective study. AIDS. 2019 Aug 1;33(10):1619-1622. doi: 10.1097/QAD.0000000000002260.

  PMID: 31306167 DERIVED

• Kiweewa FM, Brown E, Mishra A, Nair G, Palanee-Phillips T, Mgodi N, Nakabiito C, Chakhtoura N, Hillier SL, Baeten JM; MTN-020/ASPIRE Study Team. Acquisition of Sexually Transmitted Infections among Women Using a Variety of Contraceptive Options: A prospective Study among High-risk African Women. J Int AIDS Soc. 2019 Feb;22(2):e25257. doi: 10.1002/jia2.25257.

  PMID: 30816632 DERIVED

• Riddler SA, Balkus JE, Parikh UM, Mellors JW, Akello C, Dadabhai S, Mhlanga F, Ramjee G, Mayo AJ, Livant E, Heaps AL, O'Rourke C, Baeten JM; MTN-015 and MTN-020/ASPIRE Study Teams. Clinical and Virologic Outcomes Following Initiation of Antiretroviral Therapy Among Seroconverters in the Microbicide Trials Network-020 Phase III Trial of the Dapivirine Vaginal Ring. Clin Infect Dis. 2019 Jul 18;69(3):523-529. doi: 10.1093/cid/ciy909.

  PMID: 30346511 DERIVED

• Mensch BS, Richardson BA, Husnik M, Brown ER, Kiweewa FM, Mayo AJ, Baeten JM, Palanee-Phillips T, van der Straten A; MTN-020/ASPIRE study team. Vaginal Ring Use in a Phase 3 Microbicide Trial: A Comparison of Objective Measures and Self-reports of Non-adherence in ASPIRE. AIDS Behav. 2019 Feb;23(2):504-512. doi: 10.1007/s10461-018-2261-8.

  PMID: 30218318 DERIVED

• Baeten JM, Palanee-Phillips T, Brown ER, Schwartz K, Soto-Torres LE, Govender V, Mgodi NM, Matovu Kiweewa F, Nair G, Mhlanga F, Siva S, Bekker LG, Jeenarain N, Gaffoor Z, Martinson F, Makanani B, Pather A, Naidoo L, Husnik M, Richardson BA, Parikh UM, Mellors JW, Marzinke MA, Hendrix CW, van der Straten A, Ramjee G, Chirenje ZM, Nakabiito C, Taha TE, Jones J, Mayo A, Scheckter R, Berthiaume J, Livant E, Jacobson C, Ndase P, White R, Patterson K, Germuga D, Galaska B, Bunge K, Singh D, Szydlo DW, Montgomery ET, Mensch BS, Torjesen K, Grossman CI, Chakhtoura N, Nel A, Rosenberg Z, McGowan I, Hillier S; MTN-020-ASPIRE Study Team. Use of a Vaginal Ring Containing Dapivirine for HIV-1 Prevention in Women. N Engl J Med. 2016 Dec 1;375(22):2121-2132. doi: 10.1056/NEJMoa1506110. Epub 2016 Feb 22.

  PMID: 26900902 DERIVED

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Limitations and Caveats

Dapivirine residual levels in used rings and dapivirine plasma concentrations are two objective measures of adherence to DVR ring use; however, they were found to be an imperfect measure of adherence as they cannot distinguish different patterns of use during the month. In addition, self-reported adherence based on the adherence questionnaires was also considered to have limitations.

Results Point of Contact

• Title: Dr John Steytler
• Organization: International Partnership for Microbicides

jsteytler@ipmglobal.org

+27218602300

Study Officials

• Jared Baeten, MD, PhD

  International Clinical Research Center, Department of Global Health, University of Washington

  STUDY CHAIR

• Thesla Palanee, PhD

  Wits Reproductive Health and HIV Institute (WRHI), Research Centre

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2012
• First Posted: June 12, 2012
• Study Start: July 24, 2012
• Primary Completion: July 3, 2015
• Study Completion: December 1, 2015
• Last Updated: December 21, 2022
• Results First Posted: December 16, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

MA (2); ZA (3); ZI (1); UG (1)