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

NCT03762772 | Completed Phase 1 FDA Drug

• 1 other identifier: A18-146
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hiv; HSV

Keywords

HIV; TAF; EVG; Prevention; Vaginal Insert

Outcome Measures

Primary Outcomes (7)

• Number of Participants with Grade 2 or higher treatment-emergent adverse events (TEAEs)

  TEAEs are defined as adverse events starting or worsening after administration of the study product; Grade is determined by the DAIDS Grading Table

  Changes from baseline up to a maximum of 12 days post-dose

• Number of participants with adverse events

  Adverse events for this outcome are those that are product-related urogenital in nature

  Changes from baseline up to a maximum of 12 days post-dose

• systemic laboratory assessments

  Number of participants with abnormal serum chemistry

  Changes from baseline up to 72 hours post-dose

• Systemic Laboratory Assessments

  Number of participants with abnormal complete blood count

  Changes from baseline up to 72 hours post-dose

• Drug Concentrations of EVG, TFV, and TAF

  Concentrations of EVG, TFV, and TAF in plasma

  From dosing to 72 hours post-dose

• Drug Concentrations of EVG, TFV, and TAF

  Concentrations of EVG, TFV, and TAF in CV fluid

  From dosing to a maximum of 12 days post-dose

• Drug Concentrations of EVG, TFV, TFV-DP, and TAF

  Concentrations of EVG, TFV, TFV-DP, TAF in CV tissue

  From dosing to 72 hours post-dose

Secondary Outcomes (5)

• Percent (%) inhibition of HIV in vaginal cell assay (Anti-HIV activity)

  Changes from baseline to 24 hours post-dose

• Percent (%) inhibition of HSV in vaginal cell assay (Anti-HSV activity)

  Changes from baseline to 24 hours post-dose

• Number of participant tissue samples demonstrating HIV-1 infectivity

  Changes from baseline to 4 hours post-dose

• Disintegration of insert

  At 4 or 24 hours post-dose (per randomized time point)

• Acceptability of insert: questionnaire

  At baseline and at 48 or 72 hours post-dose (per randomized time point)

Other Outcomes (1)

• HSV infectivity

  Changes from baseline to 24 hours post-dose

Study Arms (1)

TAF/EVG vaginal insert

EXPERIMENTAL

Post-dose sampling at 4 and 48 hours or at 24 and 72 hours, per randomization

Drug: TAF/EVG Vaginal Insert

Interventions

TAF/EVG Vaginal Insert DRUG

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

TAF/EVG vaginal insert

Eligibility Criteria

• Age: 18 Years - 50 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18 to 50 years, inclusive
• 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.
• History of regular menstrual cycles, by volunteer report (for cycling women)
• 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
• Able to communicate in spoken and written English
• Willing to give voluntary consent and sign an informed consent form
• Willing and able to comply with protocol requirements, including abstaining from vaginal activity and product use at specified times
• 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
• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• CONRAD: lead
• Eastern Virginia Medical School: collaborator
• United States Agency for International Development (USAID): collaborator

Study Sites (1)

Clinical Research Center at Eastern Virginia Medical School (NOT RECRUITING ADDITIONAL SITES)

Norfolk, Virginia, 23507, United States

Location

Related Publications (1)

• Thurman AR, Ouattara LA, Yousefieh N, Anderson PL, Bushman LR, Fang X, Hanif H, Clark M, Singh O, Doncel GF. A phase I study to assess safety, pharmacokinetics, and pharmacodynamics of a vaginal insert containing tenofovir alafenamide and elvitegravir. Front Cell Infect Microbiol. 2023 Apr 19;13:1130101. doi: 10.3389/fcimb.2023.1130101. eCollection 2023.

  PMID: 37153145 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Medical Director

  CONRAD

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: All participants will use a single combination TAF/EVG vaginal insert.

Study Record Dates

• First Submitted: November 16, 2018
• First Posted: December 4, 2018
• Study Start: December 10, 2018
• Primary Completion: March 20, 2019
• Study Completion: March 20, 2019
• Last Updated: July 16, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)