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

HIV-1 Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00799058
• Other study ID #: IPM 020
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: July 6, 2009
• Est. completion date: January 8, 2011

Study information

• Verified date: October 2022
• Source: International Partnership for Microbicides, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 128
• Est. completion date: January 8, 2011
• Est. primary completion date: January 8, 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• HIV-1 Infections
• Infections

Intervention

Drug:
• dapivirine 4789
dapivirine gel 4789, 0.05%, 2.5g applied once daily
• dapivirine gel 4759
dapivirine gel 4759, 0.05%, 2.5g applied once daily
• Drug placebo
HEC-based universal placebo gel, 2.5g applied once daily

Locations

Country	Name	City	State
United States	SNBL Clinical Pharmacology Center	Baltimore	Maryland
United States	University of Alabama at Birmingham, Alabama Microbicide Clinical Research Site (AMCRS)	Birmingham	Alabama
United States	University of Illinois at Chicago	Chicago	Illinois
United States	Albert Einstein College of Medicine	New York	New York
United States	Harbor-UCLA Medical Center	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
International Partnership for Microbicides, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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).
Secondary	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).
Secondary	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