Hiv Clinical Trial
Official title:
A Phase I Study to Assess Safety, Pharmacokinetics, and Pharmacodynamics of a Vaginal Insert Containing Tenofovir Alafenamide and Elvitegravir
Verified date | July 2019 |
Source | CONRAD |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 16 |
Est. completion date | March 20, 2019 |
Est. primary completion date | March 20, 2019 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | Female |
Age group | 18 Years to 50 Years |
Eligibility |
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: 1. Positive pregnancy test or plans to become pregnant during the course of the study 2. Currently breastfeeding or planning to breastfeed during the course of the study 3. History of sensitivity/allergy to any component of the study product, topical anesthetic, or to both silver nitrate and Monsel's solution 4. 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.) 5. Positive test for Trichomonas vaginalis (TV), Neisseria gonorrhea (GC), Chlamydia trachomatis (CT), HIV, or Hepatitis B surface antigen (HBsAg) 6. Symptomatic bacterial vaginosis (BV) 7. Chronic or acute vulvar or vaginal symptoms (pain, irritation, spotting/bleeding, discharge, etc.) 8. Known blood disorder, including deep vein thrombosis (DVT) and pulmonary embolism (PE), or those that could lead to prolonged or continuous bleeding with biopsy 9. 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. 10. Current or anticipated chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) or acetominophen for the duration of the study. 11. 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 12. 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 13. 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 |
Country | Name | City | State |
---|---|---|---|
United States | Clinical Research Center at Eastern Virginia Medical School (NOT RECRUITING ADDITIONAL SITES) | Norfolk | Virginia |
Lead Sponsor | Collaborator |
---|---|
CONRAD | Eastern Virginia Medical School, United States Agency for International Development (USAID) |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | HSV infectivity | HSV DNA fold change after ex vivo infection of CV tissue with HSV | Changes from baseline to 24 hours post-dose | |
Primary | 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 | |
Primary | 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 | |
Primary | systemic laboratory assessments | Number of participants with abnormal serum chemistry | Changes from baseline up to 72 hours post-dose | |
Primary | Systemic Laboratory Assessments | Number of participants with abnormal complete blood count | Changes from baseline up to 72 hours post-dose | |
Primary | Drug Concentrations of EVG, TFV, and TAF | Concentrations of EVG, TFV, and TAF in plasma | From dosing to 72 hours post-dose | |
Primary | 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 | |
Primary | 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 | Percent (%) inhibition of HIV in vaginal cell assay (Anti-HIV activity) | Anti-HIV activity in CV fluid | Changes from baseline to 24 hours post-dose | |
Secondary | Percent (%) inhibition of HSV in vaginal cell assay (Anti-HSV activity) | Anti-HSV activity in CV fluid | Changes from baseline to 24 hours post-dose | |
Secondary | Number of participant tissue samples demonstrating HIV-1 infectivity | p24 antigen production in CV tissue infected with HIV-1 ex vivo | Changes from baseline to 4 hours post-dose | |
Secondary | Disintegration of insert | Percent (%) disintegration at the first evaluation after dosing | At 4 or 24 hours post-dose (per randomized time point) | |
Secondary | 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 | At baseline and at 48 or 72 hours post-dose (per randomized time point) |
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