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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

Studieöversikt

Detaljerad beskrivning

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.

Studietyp

Interventionell

Inskrivning (Faktisk)

128

Fas

  • Fas 2
  • Fas 1

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

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

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år till 40 år (Vuxen)

Tar emot friska volontärer

Ja

Kön som är behöriga för studier

Kvinna

Beskrivning

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

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Förebyggande
  • Tilldelning: Randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Dubbel

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Aktiv komparator: dapivirine gel 4789
will be applied by participants once daily for 12-weeks treatment period
dapivirine gel 4789, 0.05%, 2.5g applied once daily
Andra namn:
  • TMC120
Aktiv komparator: dapivirine gel 4759
Will be applied by participants once daily for12-weeks treatment period
dapivirine gel 4759, 0.05%, 2.5g applied once daily
Andra namn:
  • TMC120
Placebo-jämförare: HEC-based placebo gel, 2.5g containing no Dapivirine
Will be applied once daily for 12-weeks treatment period
HEC-based universal placebo gel, 2.5g applied once daily
Andra namn:
  • HEC-based placebo gel, 2.5g

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
The Percentage of Women With the Composite Endpoint of Abnormal Safety Findings.
Tidsram: 12 weeks

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

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Changes in the Vaginal Flora
Tidsram: 16 weeks

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
Tidsram: 12 weeks
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
Tidsram: 12 weeks
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
Tidsram: 12 weeks
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.
Tidsram: 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 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.
Tidsram: 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 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
Tidsram: 12 weeks
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

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Utredare

  • Studiestol: Dr Annalene Nel, International Partnership for Microbicides

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

6 juli 2009

Primärt slutförande (Faktisk)

8 januari 2011

Avslutad studie (Faktisk)

8 januari 2011

Studieregistreringsdatum

Först inskickad

26 november 2008

Först inskickad som uppfyllde QC-kriterierna

26 november 2008

Första postat (Uppskatta)

27 november 2008

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

25 oktober 2022

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

24 oktober 2022

Senast verifierad

1 oktober 2022

Mer information

Termer relaterade till denna studie

Nyckelord

Andra studie-ID-nummer

  • IPM 020

Plan för individuella deltagardata (IPD)

Planerar du att dela individuella deltagardata (IPD)?

NEJ

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Kliniska prövningar på HIV-1-infektioner

Kliniska prövningar på dapivirine 4789

3
Prenumerera