Clinical Trials

MainTitle

Safety, PK, and PD Study of a Vaginal Insert Containing TAF and EVG

This study has been completed
Sponsor
CONRAD

Collaborator
Eastern Virginia Medical School
United States Agency for International Development (USAID)

Information provided by (Responsible Party)
CONRAD
ClinicalTrials.gov Identifier
NCT03762772

First received: November 16, 2018
Last updated: July 15, 2019
Last Verified: July 2019
History of Changes
Purpose

Purpose

The purpose of this Phase I study is to assess the safety, pharmacokinetics, and pharmacodynamics of a combination vaginal insert containing tenofovir alafenamide (TAF) and elvitegravir (EVG).

This study will be the first-in-human study for a vaginally administered TAF/EVG insert and will evaluate safety, PK and PD after a single dose. It is hypothesized that the combination insert will be safe and well-tolerated by study participants and that the insert will offer an expanded window of preventive activity and a regimen with flexibility and forgiveness.

Condition Intervention Phase
Hiv
HSV

Drug : TAF/EVG Vaginal Insert
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Intervention Model Description: All participants will use a single combination TAF/EVG vaginal insert.
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Phase I Study to Assess Safety, Pharmacokinetics, and Pharmacodynamics of a Vaginal Insert Containing Tenofovir Alafenamide and Elvitegravir

Further study details as provided by CONRAD:

Primary Outcome Measures

  • Number of Participants with Grade 2 or higher treatment-emergent adverse events (TEAEs) [ Time Frame: Changes from baseline up to a maximum of 12 days post-dose ]
    TEAEs are defined as adverse events starting or worsening after administration of the study product; Grade is determined by the DAIDS Grading Table
  • Number of participants with adverse events [ Time Frame: Changes from baseline up to a maximum of 12 days post-dose ]
    Adverse events for this outcome are those that are product-related urogenital in nature
  • systemic laboratory assessments [ Time Frame: Changes from baseline up to 72 hours post-dose ]
    Number of participants with abnormal serum chemistry
  • Systemic Laboratory Assessments [ Time Frame: Changes from baseline up to 72 hours post-dose ]
    Number of participants with abnormal complete blood count
  • Drug Concentrations of EVG, TFV, and TAF [ Time Frame: From dosing to 72 hours post-dose ]
    Concentrations of EVG, TFV, and TAF in plasma
  • Drug Concentrations of EVG, TFV, and TAF [ Time Frame: From dosing to a maximum of 12 days post-dose ]
    Concentrations of EVG, TFV, and TAF in CV fluid
  • Drug Concentrations of EVG, TFV, TFV-DP, and TAF [ Time Frame: From dosing to 72 hours post-dose ]
    Concentrations of EVG, TFV, TFV-DP, TAF in CV tissue
Secondary Outcome Measures:
  • Percent (%) inhibition of HIV in vaginal cell assay (Anti-HIV activity) [ Time Frame: Changes from baseline to 24 hours post-dose ]
    Anti-HIV activity in CV fluid
  • Percent (%) inhibition of HSV in vaginal cell assay (Anti-HSV activity) [ Time Frame: Changes from baseline to 24 hours post-dose ]
    Anti-HSV activity in CV fluid
  • Number of participant tissue samples demonstrating HIV-1 infectivity [ Time Frame: Changes from baseline to 4 hours post-dose ]
    p24 antigen production in CV tissue infected with HIV-1 ex vivo
  • Disintegration of insert [ Time Frame: At 4 or 24 hours post-dose (per randomized time point) ]
    Percent (%) disintegration at the first evaluation after dosing
  • Acceptability of insert: questionnaire [ Time Frame: At baseline and at 48 or 72 hours post-dose (per randomized time point) ]
    Responses to key questions on acceptability questionnaire (including prior experience with vaginal product use, initial and post-use impressions of insert, dissolution time, discharge amounts, and feelings about real-world use if insert was available for use
Other Outcome Measures:
  • HSV infectivity [ Time Frame: Changes from baseline to 24 hours post-dose ]
    HSV DNA fold change after ex vivo infection of CV tissue with HSV

Enrollment: 16
Study Start Date: December 10, 2018
Study Completion Date: March 20, 2019
Primary Completion Date: March 20, 2019 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: TAF/EVG vaginal insert
Post-dose sampling at 4 and 48 hours or at 24 and 72 hours, per randomization
Drug: TAF/EVG Vaginal Insert

1 combination vaginal insert (20mg TAF/16mg EVG)

Detailed Description:

This Phase I study aims to complete at least 16 healthy, non-pregnant, HIV-uninfected women aged 18-50 years who are not at risk for pregnancy and are at low risk for sexually transmitted infections (STIs) at one clinical site. The study will examine the safety, PK, PD, disintegration, and acceptability of vaginal inserts containing the combination of tenofovir alafenamide (TAF) and elvitegravir (EVG).
Participants will be randomized (1:1) into one of two sample collection time point groups:
[Timepoint group 1: 4 and 48 hours after using the single combination insert] or [Timepoint group 2: 24 and 72 hours after using the single combination insert]
There will be 5 scheduled visits:
Visit 1 (Screening/Enrollment): Volunteers will be consented and undergo tests and procedures to confirm they are eligible to continue in the study.
Visit 2 (Baseline): Once it has been confirmed that participants are eligible and willing to continue, they will be asked to complete a short baseline questionnaire about the insert. Participants will be randomized to Timepoint group 1 or Timepoint group 2 for sample collection and will then undergo baseline sampling [cervicovaginal (CV) fluid and tissue].
Visit 3 (Insert use and sampling): Participants will use a single combination insert of TAF/EVG in the clinic. Depending upon timepoint randomization, percentage disintegration of the vaginal inserts will be assessed at either 4 hours or 24 hours, and PK and PD sample collection (plasma, CV fluid, and CV tissue) will occur. Participants will also be asked to complete a short acceptability questionnaire.
Visit 4 (Post-Dose Sampling): Participants will undergo sample collection of blood for safety and PK evaluations; and CV fluid and CV tissue for PK at either 48 hours or 72 hours depending upon timepoint randomization.
Visit 5 (Post-Dose Sampling): Participants will undergo a PK sample collection (CV fluid) 7 (±2) days post dose. Participants will be asked about adverse events and concomitant medications taken. Participants will then be exited from the study, unless they have symptoms that require follow-up.
There will be 5 scheduled visits over approximately 1-3 months.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years to 50 Years  
Sexes Eligible for Study: Female  
Accepts Healthy Volunteers: Yes  

Criteria

Inclusion Criteria:

  1. Age 18 to 50 years, inclusive
  2. General good health (by volunteer history and per investigator judgment) without any clinically significant systemic disease (including, but not limited to significant liver disease/hepatitis, gastrointestinal disease, kidney disease, thyroid disease, bone disease, and diabetes) and with an intact uterus and cervix.
  3. History of regular menstrual cycles, by volunteer report (for cycling women)
  4. History of Pap smears and follow-up consistent with standard clinical practice as outlined in the Study Manual or willing to undergo a Pap smear at Visit 1
  5. Able to communicate in spoken and written English
  6. Willing to give voluntary consent and sign an informed consent form
  7. Willing and able to comply with protocol requirements, including abstaining from vaginal activity and product use at specified times
  8. Must be protected from pregnancy by one of the following:
    • Hormonal methods, except vaginal rings and DMPA
    • Copper IUD
    • Sterilization of participant or partner
    • Consistent condom use
    • Abstinence from penile-vaginal intercourse
    • Same sex relationship
  9. If in a relationship, must be in a mutually monogamous relationship with a partner who is not known to be HIV positive and has no known risk of sexually transmitted infections (STIs)

  • Exclusion Criteria:
  • Positive pregnancy test or plans to become pregnant during the course of the study
  • Currently breastfeeding or planning to breastfeed during the course of the study
  • History of sensitivity/allergy to any component of the study product, topical anesthetic, or to both silver nitrate and Monsel's solution
  • In the last three months, diagnosed with or treated for any STI (For HSV, ideally no outbreaks in the past year. More than two outbreaks in previous 12 month period is exclusionary.)
  • Positive test for Trichomonas vaginalis (TV), Neisseria gonorrhea (GC), Chlamydia trachomatis (CT), HIV, or Hepatitis B surface antigen (HBsAg)
  • Symptomatic bacterial vaginosis (BV)
  • Chronic or acute vulvar or vaginal symptoms (pain, irritation, spotting/bleeding, discharge, etc.)
  • Known blood disorder, including deep vein thrombosis (DVT) and pulmonary embolism (PE), or those that could lead to prolonged or continuous bleeding with biopsy
  • NSAIDS, systemic corticosteroids (e.g. dexamethasone), Endothelin Receptor Antagonists (e.g bosentan), antibiotics, Anticonvulsants (e.g. carbamazepine, oxcarbazepine, phenobarbital, phenytoin), Antimycobacterials (Rifbutin, Rifampin, Rifapentine) anticoagulants or other drugs known to prolong bleeding and/or clotting, antifungals (i.e ketoconazole), or antivirals or antiretroviral (e.g. acyclovir, valacyclovir, Viread®, Atripla®, Emtriva®, or Complera®), St. John's Wort or drugs that may interact with TAF or EVG as specified in the Vitekta and Vemlidy Investigator Brochure, should not be used during the study.
  • Current or anticipated chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) or acetominophen for the duration of the study.
  • Participation in any other investigational trial with use of a drug/device within the last 30 days or planned participation in any other investigational trial with use of a drug/device during the study
  • Grade 2 or higher laboratory abnormality, per the Division of AIDS, National Institute of Allergy and Infectious Disease (DAIDS) Table for Grading the Severity of Adverse Events, or clinically significant laboratory abnormality as determined by the clinician
  • Abnormal finding on laboratory or physical examination or a social or medical condition in the volunteer which, in the opinion of the investigator, would make participation in the study unsafe or would complicate interpretation of data

    contacts and locations

    Contacts and Locations

    Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

    Please refer to this study by its ClinicalTrials.gov identifier: NCT03762772

    Locations

    United States, Virginia
    Clinical Research Center at Eastern Virginia Medical School (NOT RECRUITING ADDITIONAL SITES)
    Norfolk, Virginia, United States, 23507

    Sponsors and Collaborators

    CONRAD
    Eastern Virginia Medical School
    United States Agency for International Development (USAID)

    Investigators

    Study Director: Medical Director CONRAD
    More Information

    More Information


    Responsible Party: CONRAD  
    ClinicalTrials.gov Identifier: NCT03762772   History of Changes  
    Other Study ID Numbers: A18-146  
    Study First Received: November 16, 2018  
    Last Updated: July 15, 2019  
    Individual Participant Data    
    Plan to Share IPD: No  

    Studies a U.S. FDA-regulated Drug Product: Yes  
    Studies a U.S. FDA-regulated Device Product: No  
    Product Manufactured in and Exported from the U.S.: No  

    Keywords provided by CONRAD:

    HIV
    TAF
    EVG
    Prevention
    Vaginal Insert

    ClinicalTrials.gov processed this data on August 16, 2019
    This information is provided by ClinicalTrials.gov.