Safety, PK, and PD Study of a Vaginal Insert Containing TAF and EVG
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|ClinicalTrials.gov Identifier: NCT03762772|
Recruitment Status : Completed
First Posted : December 4, 2018
Last Update Posted : July 16, 2019
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 or disease||Intervention/treatment||Phase|
|Hiv HSV||Drug: TAF/EVG Vaginal Insert||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||16 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||All participants will use a single combination TAF/EVG vaginal insert.|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study to Assess Safety, Pharmacokinetics, and Pharmacodynamics of a Vaginal Insert Containing Tenofovir Alafenamide and Elvitegravir|
|Actual Study Start Date :||December 10, 2018|
|Actual Primary Completion Date :||March 20, 2019|
|Actual Study Completion Date :||March 20, 2019|
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)
- 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
- 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
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03762772
|United States, Virginia|
|Clinical Research Center at Eastern Virginia Medical School (NOT RECRUITING ADDITIONAL SITES)|
|Norfolk, Virginia, United States, 23507|
|Study Director:||Medical Director||CONRAD|