A Safety Study of Two Dapivirine (TMC120) Vaginal Gels in the United States

A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED PHASE I/II TRIAL TO EVALUATE THE SAFETY OF DAPIVIRINE GEL 4759, 0.05% 2.5g AND DAPIVIRINE GEL 4789, 0.05% 2.5g FORMULATIONS AS COMPARED TO THE VAGINAL HEC-BASED UNIVERSAL PLACEBO GEL, 2.5g IN HEALTHY HIV-NEGATIVE WOMEN

A double-blind, randomized, placebo-controlled Phase I/II trial to evaluate the safety of dapivirine Gel 4759, 0.05% 2.5 g and dapivirine Gel 4789, 0.05% 2.5 g formulations as compared to the vaginal HEC-based Universal placebo gel, 2.5 g in healthy HIV-negative women

Study Overview

• Status: Completed
• Conditions: HIV-1 Infections
• Intervention / Treatment: Drug: dapivirine 4789; Drug: dapivirine gel 4759; Drug: Drug placebo

Detailed Description

This was a double-blind, randomized, placebo-controlled trial, to be conducted over 10 months at five research centers in the USA among 180 healthy, sexually active women, to assess the safety and acceptability of dapivirine Gel 4759, 0.05% 2.5 g, and dapivirine Gel 4789, 0.05% 2.5 g, both vaginal microbicides containing dapivirine, compared to the vaginal HEC-based Universal placebo gel, 2.5 g, containing no active ingredient, used once daily for a period of 12 weeks.

• Study Type: Interventional
• Enrollment (Actual): 128
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham, Alabama Microbicide Clinical Research Site (AMCRS)
  • California
    • Torrance, California, United States, 90502
      • Harbor-UCLA Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • SNBL Clinical Pharmacology Center
  • New York
    • New York, New York, United States, 10461
      • Albert Einstein College Of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Women 18 to 40 years of age inclusive who can give written informed consent
2. Available for all visits and consent to follow all procedures scheduled for the trial
3. Healthy and self-reported sexually active
4. HIV-negative as determined by an HIV test at time of enrollment
5. Willing to be on a stable form of contraception
6. In the absence of the use of exogenous hormone(s), have a self-reported regular menstrual cycle
7. Upon pelvic/speculum examination and colposcopy at the enrollment visit, the cervix and vagina appear normal as determined by qualified research center staff
8. Asymptomatic for genital infections at the time of enrollment
9. Willing to refrain from use of vaginal products or objects for 14 days prior to enrollment and for the duration of the trial.
10. Documentation of no abnormality on Pap smear within 90 days prior to randomization;
11. Willing to answer acceptability and adherence questionnaires throughout the trial
12. Willing to refrain from participation in any other research trial for the duration of this trial
13. Willing to provide adequate locator information for trial retention purposes and be reachable per local standard procedures

14. Willing to abstain from all the following criteria beginning 48 hours prior to each trial visit:

    • Vaginal intercourse
    • Oral contact with her genitalia
    • Internal vaginal washing
    • Penetration of the vagina by fingers, sex toys, or any other objects, including medications

15. Willing to abstain from all of the following for 3 days after biopsy procedures:

    • Vaginal intercourse
    • Oral contact with her genitalia
    • Internal vaginal washing
    • Penetration of the vagina by fingers, sex toys, or any other objects, including medications

Exclusion Criteria:

1. Currently pregnant or having had their last pregnancy outcome within 3 months prior to screening
2. Currently breast-feeding, or having breastfed within 3 months prior to screening
3. Receipt of any investigational agent within 60 days prior to screening
4. Previously participated in any HIV vaccine trial
5. Untreated urogenital infections within 2 weeks prior to enrollment
6. Presence of any abnormal physical finding on the vulva, vaginal walls or cervix during pelvic/speculum examination and/or colposcopy
7. History of significant urogenital or uterine prolapse, undiagnosed vaginal bleeding, or urethral obstruction
8. Pap smear result at screening that requires cryotherapy, biopsy or treatment (other than for infection)
9. History of symptomatic or asymptomatic HSV-2
10. Any Grade 2, 3 or 4 hematology, chemistry or urinalysis laboratory abnormality at baseline
11. Unexplained, undiagnosed abnormal bleeding per vagina during or following vaginal intercourse; or urogenital surgery within 90 days prior to enrollment
12. Any history of anaphylaxis or severe allergy resulting in angioedema; or a history of sensitivity/allergy to latex
13. Any serious acute, chronic or progressive disease
14. Any condition(s) that, in the opinion of the Investigator, might interfere with adherence to trial requirements or evaluation of the trial objectives

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: dapivirine gel 4789; will be applied by participants once daily for 12-weeks treatment period	Drug: dapivirine 4789; dapivirine gel 4789, 0.05%, 2.5g applied once daily; Other Names: TMC120
Active Comparator: dapivirine gel 4759; Will be applied by participants once daily for12-weeks treatment period	Drug: dapivirine gel 4759; dapivirine gel 4759, 0.05%, 2.5g applied once daily; Other Names: TMC120
Placebo Comparator: HEC-based placebo gel, 2.5g containing no Dapivirine; Will be applied once daily for 12-weeks treatment period	Drug: Drug placebo; HEC-based universal placebo gel, 2.5g applied once daily; Other Names: HEC-based placebo gel, 2.5g

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Women With the Composite Endpoint of Abnormal Safety Findings.	A composite endpoint was defined as the percentage of participants with any post-baseline abnormal finding from pelvic/speculum examination, colposcopy finding, STI diagnoses, laboratory test of DAIDS grade 3 or higher and any product-related AE. DAIDS severity grades are defined as follows: Grade 1 = mild Grade 2 = moderate Grade 3 = severe Grade 4 = potentially life-threatening Grade 5 = death	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the Vaginal Flora	Cervicovaginal fluid specimens will be obtained to determine vaginal flora before first gel application and at Visits 3, 5, and 6. Appropriate statistical analyses incorporating repeated measures will be used to assess the changes in the vaginal flora in women using Dapivirine Gel 4759, 0.05% 2.5g, Dapivirine Gel 4789, 0.05% 2.5g or the vaginal HEC-based universal placebo gel, 2.5g. Nugent scores were used to assess changes in vaginal flora, and were categorized into three levels: (1) negative for BV (score: 0-3); (2) altered vaginal flora (score: 4-6); and (3) BV (score: 7-10).	16 weeks
The Distribution of Dapivirine Levels Observed in Plasma Samples at Each Specified Time Point	Dapivirine levels observed in plasma will be summarized using simple descriptive statistics.	12 weeks
The Adherence to Once Daily Application of a Vaginal Microbicide Gel Over a 12-week Period in Healthy, Sexually Active, HIV-negative Women	Adherence is defined as the percentage of participants who used the gel each day of the preceding 14 days, based on participant self reports.	12 weeks
Changes in the Vaginal pH	Cervicovaginal fluid specimens will be obtained to determine vaginal pH before first gel application and at screening, enrolment and visit 5 (week 12). Appropriate statistical analyses incorporating repeated measures will be used to assess the changes in the vaginal pH in women using Dapivirine Gel 4759, 0.05% 2.5g, Dapivirine Gel 4789, 0.05% 2.5g or the vaginal HEC-based universal placebo gel, 2.5g.	12 weeks
The Distribution of Dapivirine Levels Observed in Vaginal Fluid at Each Specified Time Point.	The distribution of dapivirine levels observed in each type of sample will be summarized using simple descriptive statistics. In addition, the proportion of women with detectable dapivirine concentrations will be calculated for each type of sample at each collection time point. Exploratory analyses of dapivirine concentration data will also be performed to take into account information reported in a diary regarding menses and tampon use throughout the trial.	12 weeks. Measured at 2, 4, and 8 weeks post-enrolment and at one of these at week 12; 24, 48, or 72 hours after gel discontinuation. (Participants were randomized to have vaginal fluid samples collected at one of these visits (5a, 5b, or 5c).
The Distribution of Dapivirine Levels Observed in Vaginal Tissue at Each Specified Time Point.	The distribution of dapivirine levels observed in vaginal tissue sample will be summarized using simple descriptive statistics.	12 weeks. Measured at 2, 4, and 8 weeks post-enrolment and at one of these at week 12; 24, 48, or 72 hours after gel discontinuation. (Participants were randomized to have vaginal fluid samples collected at one of these visits (5a, 5b, or 5c).
Acceptability of Once Daily Application of a Vaginal Microbicide Gel Over a 12-week Period in Healthy, Sexually Active, HIV-negative Women	Acceptability was assessed as the percentage of participants at week 12 who were willing to use the gel every day if proven to prevent HIV.	12 weeks

Collaborators and Investigators

• Sponsor: International Partnership for Microbicides, Inc.
• Investigators: Study Chair: Dr Annalene Nel, International Partnership for Microbicides

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2009
• Primary Completion (Actual): January 8, 2011
• Study Completion (Actual): January 8, 2011

Study Registration Dates

• First Submitted: November 26, 2008
• First Submitted That Met QC Criteria: November 26, 2008
• First Posted (Estimate): November 27, 2008

Study Record Updates

• Last Update Posted (Actual): October 25, 2022
• Last Update Submitted That Met QC Criteria: October 24, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: HIV-1 infections
• Additional Relevant MeSH Terms: Infections; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Dapivirine
• Other Study ID Numbers: IPM 020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO