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

NCT00799058 | Completed Phase 1 Results DMC

• 1 other identifier: IPM 020
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 5

Brief 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

Conditions

HIV-1 Infections

Keywords

HIV-1 infections

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Changes in the Vaginal Flora

  16 weeks

• The Distribution of Dapivirine Levels Observed in Plasma Samples at Each Specified Time Point

  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

  12 weeks

• Changes in the Vaginal pH

  12 weeks

• The Distribution of Dapivirine Levels Observed in Vaginal Fluid at Each Specified Time Point.

  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).

Study Arms (3)

dapivirine gel 4789

ACTIVE COMPARATOR

will be applied by participants once daily for 12-weeks treatment period

Drug: dapivirine 4789

dapivirine gel 4759

ACTIVE COMPARATOR

Will be applied by participants once daily for12-weeks treatment period

Drug: dapivirine gel 4759

HEC-based placebo gel, 2.5g containing no Dapivirine

PLACEBO COMPARATOR

Will be applied once daily for 12-weeks treatment period

Drug: Drug placebo

Interventions

dapivirine 4789 DRUG

dapivirine gel 4789, 0.05%, 2.5g applied once daily

Also known as: TMC120

dapivirine gel 4789

dapivirine gel 4759 DRUG

dapivirine gel 4759, 0.05%, 2.5g applied once daily

Also known as: TMC120

dapivirine gel 4759

Drug placebo DRUG

HEC-based universal placebo gel, 2.5g applied once daily

Also known as: HEC-based placebo gel, 2.5g

HEC-based placebo gel, 2.5g containing no Dapivirine

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Women 18 to 40 years of age inclusive who can give written informed consent
• Available for all visits and consent to follow all procedures scheduled for the trial
• Healthy and self-reported sexually active
• HIV-negative as determined by an HIV test at time of enrollment
• Willing to be on a stable form of contraception
• In the absence of the use of exogenous hormone(s), have a self-reported regular menstrual cycle
• Upon pelvic/speculum examination and colposcopy at the enrollment visit, the cervix and vagina appear normal as determined by qualified research center staff
• Asymptomatic for genital infections at the time of enrollment
• Willing to refrain from use of vaginal products or objects for 14 days prior to enrollment and for the duration of the trial.
• Documentation of no abnormality on Pap smear within 90 days prior to randomization;
• Willing to answer acceptability and adherence questionnaires throughout the trial
• Willing to refrain from participation in any other research trial for the duration of this trial
• Willing to provide adequate locator information for trial retention purposes and be reachable per local standard procedures
• Willing to abstain from all the following criteria beginning 48 hours prior to each trial visit:
• Vaginal intercourse

You may not qualify if:

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

Sponsors & Collaborators

• International Partnership for Microbicides, Inc.: lead

Study Sites (5)

University of Alabama at Birmingham, Alabama Microbicide Clinical Research Site (AMCRS)

Birmingham, Alabama, 35294, United States

Location

Harbor-UCLA Medical Center

Torrance, California, 90502, United States

Location

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

SNBL Clinical Pharmacology Center

Baltimore, Maryland, 21201, United States

Location

Albert Einstein College of Medicine

New York, New York, 10461, United States

Location

MeSH Terms

Interventions

Dapivirine

Limitations and Caveats

Concluding a general trend in vaginal fluid data is, however, difficult as overall individual fluid levels for the two gel formulations were in the same range and differences based on median values were not consistent across visits.

Results Point of Contact

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

jsteytler@ipmglobal.org

Study Officials

• Dr Annalene Nel

  International Partnership for Microbicides

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Potential participants who provide inform consent will be invited to screen for the trial. All participants who consent to participate in the trial and meet specified inclusion/exclusion criteria will be invited to enrol. At enrolment women will be randomly assigned in a 1:1:1 ratio to one of three groups.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: All enrolled participants will apply gel on a daily basis for 12 weeks, with clinical follow-up visits at weeks 2,4,8 and 12 to monitor safety and acceptability, and a final visit 4 weeks post gel discontinuation (Visit 6, week 16) Dapivirine concentration will be measured in blood and vaginal fluid and cervical tissue.

Study Record Dates

• First Submitted: November 26, 2008
• First Posted: November 27, 2008
• Study Start: July 6, 2009
• Primary Completion: January 8, 2011
• Study Completion: January 8, 2011
• Last Updated: October 25, 2022
• Results First Posted: October 25, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)