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

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

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

Official Title
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A Multi-Centre, Randomised, Double-Blind, Placebo-Controlled Safety and Efficacy Trial of a Dapivirine Vaginal Matrix Ring in Healthy HIV-Negative Women

Conditions
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HIV Infections

Intervention / Treatment
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* Combination Product: Placebo Vaginal Ring
* Combination Product: Dapivirine Vaginal Ring, 25 mg


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Vaginal Ring<br>Vaginal Ring containing 0.0 mg Dapivirine | Combination Product: Placebo Vaginal Ring<br>* Dapivirine Vaginal Ring containing 0.0 mg of dapivirine<br>|
| Experimental: Dapivirine Vaginal Ring<br>Vaginal Ring containing 25mg of Dapivirine | Combination Product: Dapivirine Vaginal Ring, 25 mg<br>* Dapivirine Vaginal Ring containing 25 mg of dapivirine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HIV-1 Seroconversion According to Comprehensive HIV Testing Algorithm. | HIV-1 seroconversion measured by rapid and specialised laboratory testing according to the comprehensive HIV testing algorithm. | 24 months | 
| All Adverse Events | Self-reports, physical examination, gynaecological assessments, including pelvic/speculum examination, laboratory tests and other indicated investigations. All AEs will be reported, regardless of grade or relatedness. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Incidence Rate of HIV-2 Seroconversion. | Rapid and specialised laboratory testing according to the comprehensive HIV testing algorithm in Appendix C of protocol. | 24 months | 
| The Incidence of Curable STIs | The percentage of participants testing positive for any STI (gonorrhoea, chlamydia, trichomonas, syphilis) will be assessed. | 24 months | 
| Percentage of Participants With Pregnancy in Each Trial Arm Over the IP Use Period; | The percentage of participants with pregnancies in each treatment group. For each treatment group, the numerator will include the number of participants that had a positive urine pregnancy test during the trial period. | 24 months | 
| The Percentage of Women Who Report Adherence to the Use of the Vaginal Ring Inserted Once Every 4 Weeks Over the Trial Period; | Questionnaires and qualitative data regarding sexual behaviour and adherence to the use of a vaginal ring inserted once every 4 weeks over the trial period. Dapivirine residual levels in used rings and dapivirine plasma concentrations are two objective measures of adherence to DVR ring use, | 24 months | 
| The Percentage of Women Who Report the Use of the Vaginal Ring as Acceptable; | Questionnaires and qualitative data regarding the acceptability of use of a vaginal ring inserted once every 4 weeks over the trial period; Number of participants with positive response. Response of 'likely' or 'very likely' to the question: 'If in the future a vaginal ring was available that provided some protection against HIV, and it was similar to the one you used in this trial, how likely would you be to keep it inserted in your vagina every day?' | 24 months | 
| The Percentage of Participants With HIV-1 Drug Resistance Mutations Among Participants Who Acquire HIV-1. | The analysis of HIV-1 drug resistance will be primarily descriptive in nature, and will depend on the pattern of resistance mutations observed in the HIV-1 seroconverters. The proportion of HIV-1 seroconverters with at least one HIV-1 drug resistant mutation will be presented overall, and by treatment arm, with corresponding 95% CIs. | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV Infections, Anti-HIV agents, HIV-1