HivPhase 1NCT03762772
Safety, PK, and PD Study of a Vaginal Insert Containing TAF and EVG
A Phase 1 study testing TAF/EVG Vaginal Insert in people with Hiv and HSV, run by CONRAD at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 50 years, women onlyHealthy volunteers can take part
- What is being tested?
- TAF/EVG Vaginal Insert
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Dec 2018to 20 Mar 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
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- 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)
Who cannot join
- 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)
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Clinical Research Center at Eastern Virginia Medical School (NOT RECRUITING ADDITIONAL SITES)
Norfolk, Virginia, 23507
About this study
Official title: A Phase I Study to Assess Safety, Pharmacokinetics, and Pharmacodynamics of a Vaginal Insert Containing Tenofovir Alafenamide and Elvitegravir
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.
Read the 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.
- Being tested
- TAF/EVG Vaginal Insert
- Keywords
- HIV, TAF, EVG, Prevention, Vaginal Insert
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TAF/EVG Vaginal InsertDrug
1 combination vaginal insert (20mg TAF/16mg EVG)
| Study group | Role | What they receive |
|---|---|---|
| TAF/EVG vaginal insert | Experimental | Post-dose sampling at 4 and 48 hours or at 24 and 72 hours, per randomization Receives: Drug: TAF/EVG Vaginal Insert |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: Changes from baseline up to a maximum of 12 days post-dose
systemic laboratory assessments
Number of participants with abnormal serum chemistry
Measured: Changes from baseline up to 72 hours post-dose
Systemic Laboratory Assessments
Number of participants with abnormal complete blood count
Measured: Changes from baseline up to 72 hours post-dose
Drug Concentrations of EVG, TFV, and TAF
Concentrations of EVG, TFV, and TAF in plasma
Measured: From dosing to 72 hours post-dose
Drug Concentrations of EVG, TFV, and TAF
Concentrations of EVG, TFV, and TAF in CV fluid
Measured: 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
Measured: From dosing to 72 hours post-dose
Secondary outcomes (5)
Percent (%) inhibition of HIV in vaginal cell assay (Anti-HIV activity)
Anti-HIV activity in CV fluid
Measured: Changes from baseline to 24 hours post-dose
Percent (%) inhibition of HSV in vaginal cell assay (Anti-HSV activity)
Anti-HSV activity in CV fluid
Measured: Changes from baseline to 24 hours post-dose
Number of participant tissue samples demonstrating HIV-1 infectivity
p24 antigen production in CV tissue infected with HIV-1 ex vivo
Measured: Changes from baseline to 4 hours post-dose
Disintegration of insert
Percent (%) disintegration at the first evaluation after dosing
Measured: At 4 or 24 hours post-dose (per randomized time point)
Acceptability of insert: questionnaire
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
Measured: At baseline and at 48 or 72 hours post-dose (per randomized time point)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2018
- Study start10 Dec 2018
- Primary completion20 Mar 2019
- Study completion20 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HivStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- All participants will use a single combination TAF/EVG vaginal insert.
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- CONRAD
- Sponsor type
- University, hospital or other
- Collaborators
- Eastern Virginia Medical School, United States Agency for International Development (USAID)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, CONRAD
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03762772
- Sponsor's protocol ID
- A18-146
- Status last verified
- Jul 2019
- First submitted
- 16 Nov 2018
- Last updated
- 16 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 37153145
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study to Assess Safety, Pharmacokinetics, and Pharmacodynamics of a Vaginal Insert Containing Tenofovir Alafenamide and Elvitegravir
- ClinicalTrials.gov ID
- NCT03762772
- Acronym / sponsor ID
- A18-146
- Keywords
- HIV, TAF, EVG, Prevention, Vaginal Insert
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- CONRADUniversity, hospital or other
- Collaborators
- Eastern Virginia Medical School, United States Agency for International Development (USAID)
- Study start
- 10 Dec 2018 (actual)
- Primary completion
- 20 Mar 2019 (actual)
- Study completion
- 20 Mar 2019 (actual)
- First posted
- 4 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- All participants will use a single combination TAF/EVG vaginal insert.
| Arm | Type | Receives |
|---|---|---|
| TAF/EVG vaginal insert | Experimental | Drug: TAF/EVG Vaginal InsertPost-dose sampling at 4 and 48 hours or at 24 and 72 hours, per randomization |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- 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
Key exclusion criteria (13 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TAF/EVG Vaginal Insert1 combination vaginal insert (20mg TAF/16mg EVG) | Drug | TAF/EVG vaginal insert |
Primary outcome
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
5 secondary outcomes
Percent (%) inhibition of HIV in vaginal cell assay (Anti-HIV activity)
Time frame: Changes from baseline to 24 hours post-dose
Percent (%) inhibition of HSV in vaginal cell assay (Anti-HSV activity)
Time frame: Changes from baseline to 24 hours post-dose
Number of participant tissue samples demonstrating HIV-1 infectivity
Time frame: Changes from baseline to 4 hours post-dose
Disintegration of insert
Time frame: At 4 or 24 hours post-dose (per randomized time point)
Acceptability of insert: questionnaire
Time frame: At baseline and at 48 or 72 hours post-dose (per randomized time point)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2019.
- Derived from this study: PubMed 37153145Thurman 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
CONRAD
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TAF/EVG Vaginal Insert in people with Hiv and HSV, run by CONRAD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03762772, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2019.