- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03255915
PrEP-Pod-IVR (TDF-FTC/Placebo IVR 28 Day Crossover Study) (PrEP-Pod-IVR)
Randomized Order, Controlled, Double Blind, Crossover Early Phase 1 Pilot Study to Assess Safety and Pharmacokinetics of a Tenofovir Disoproxil Fumarate and Emtricitabine (TDF-FTC) Releasing IVR Over 28 Days Compared to Placebo
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Early Phase 1
Contacts and Locations
Study Locations
-
-
Texas
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Galveston, Texas, United States, 77555
- University of Texas Medical Branch
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Age of 18 through 45 years at screening, verified per site SOP
- Female participants, born female
- Not pregnant or breastfeeding
- Availability to return for all study visits, barring unforeseen circumstances
Willing and able to
- communicate in English
- provide written informed consent to take part in the study
- provide adequate locator information, as defined in site SOP
- complete all required study procedures, including phone surveys, daily vaginal swabs, and reliably store swabs in freezer
Must agree
- not to participate in other concurrent interventional and/or drug trials
- to use study-provided condoms for vaginal or anal intercourse for the duration of the study
- to abstain from use of any vaginal products (e.g., lubricants, feminine hygiene products, vaginally administered contraceptive products, sex toys) other than study products for the duration of the study beginning at enrollment Note: Tampons may be used during menses, but must be discontinued 72 hours prior to study visits and for 7 days after biopsy procedures. Menstrual pads will be provided to participants.
- to abstain from receptive oral, vaginal, or anal intercourse during the first week after each pod-IVR insertion and for 2 days before and 7 days after biopsy procedures
- to abstain from insertion of anything in the vagina (e.g., tampon, finger, sex toy, lubricants, medication, douche) during the first week after each pod-IVR insertion and for 2 days before and 7 days after biopsy procedures
- Understands and agrees to local STI reporting requirements
- HIV-1 seronegative at screening
- Must be in general good health in the opinion of the investigator
- Regular menstrual cycles of approximately 21 to 35 days apart with no untreated intermenstrual menstrual bleeding Note: This criterion is not applicable to participants using continuous combination oral contraceptive pills or progestin-only methods (such as Depo-Provera or levonorgestrel-releasing IUD), as the absence of regular menstrual cycles is an expected, normal consequence in this context.
- Satisfactory cervical Pap result in the 36 calendar months prior to Enrollment consistent with Grade 0 according to the Female Genital Grading Table for Use in Microbicide Studies [Addendum 1, Dated November 2007], or if Grade 1 or higher Pap result has had a satisfactory evaluation with no treatment required per American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines in the 12 calendar months prior to Enrollment
Using an effective method of contraception and intending to continue use of an effective method for the duration of study participation. Acceptable methods include:
- hormonal methods (except contraceptive vaginal rings)
- IUD
- sterilization of participant or partner
In addition to the criteria listed above, participants who agree to have rectal biopsies collected must meet the following criteria:
- Must agree to abstain from insertion of anything in the rectum (e.g., finger, sex toy, lubricants, medication, enema) during the first week after each pod-IVR insertion and for 2 days before and 7 days after biopsy procedures
Male sexual partner(s) who meet the following criteria are eligible for inclusion in the study:
- Age of 18 years or over
- Has a female sexual partner enrolled in the study
Willing and able to
- communicate in English
- provide written informed consent to take part in the study
- provide adequate locator information, as defined in site SOP
- complete in-depth interview via video conference
Exclusion Criteria:
Individuals who meet any of the following criteria will be excluded from the study:
- Undergoing or completed gender reassignment
Participant reports any of the following at Screening:
- Has plans to relocate away from the study site area during the period of study participation
- Pregnant, less than 3 months post-partum, or lactating
- Intends to become pregnant during the period of study participation
- Current or planned use of an IVR
- Known HIV-infected partners
- Non-therapeutic injection drug use in the 6 months prior to screening
- History of autoimmune disease
- History of toxic shock syndrome
- History of adverse reaction to TDF, FTC, silicone, or microcrystalline cellulose
- PrEP or Post-exposure prophylaxis for HIV exposure within 6 months prior to screening
- Use of systemic immunomodulatory medications within the 4 weeks prior to the Enrollment
- Use of vaginally or rectally administered medications or products (including condoms) containing Nonoxynol-9 (N-9) within the 4 weeks prior to the Enrollment
- Participating in another research study involving drugs or medical devices within the 4 weeks or 5 half-lives (if known) prior to the Enrollment
- Gynecologic or genital procedure (e.g., tubal ligation, dilation and curettage, piercing) within 60 days prior to Enrollment
Note: Colposcopy and cervical biopsies for evaluation of an abnormal Pap smear as well as IUD removal are not exclusionary
Per participant report at screening, anticipated use and/or unwillingness to abstain from the following medications during the period of study participation:
- Heparin, including Lovenox® (enoxaparin sodium)
- Warfarin
- Plavix® (clopidogrel bisulfate)
- Any other drugs that are associated with increased likelihood of bleeding following mucosal biopsy (e.g., daily high dose aspirin, Pradaxa®)
- NSAID use for 5 half-lives prior to biopsy (e.g. ibuprofen for 1 day, naproxen for 4 days).
- Rectally or vaginally administered medications (including over-the-counter products)
- History of significant gastrointestinal bleeding in the opinion of the investigator
Abnormalities of the cervical, vaginal, or colorectal mucosa, or significant symptom(s), which in the opinion of the clinician represents a contraindication to protocol-required biopsies (including but not limited to presence of any unresolved injury, infectious or inflammatory condition of the local mucosa, and presence of symptomatic external hemorrhoids). Erythema is not exclusionary.
• Includes any clinically apparent Grade 2 or higher pelvic examination finding (observed by study staff) at Screening or Enrollment, as per the Female Genital Grading Table for Use in Microbicide Studies [Addendum 1, Dated November 2007]
At screening: participant-reported symptoms and/or clinical or laboratory diagnosis of active rectal or reproductive tract infection requiring treatment per current CDC guidelines or symptomatic urinary tract infection (UTI). Infections requiring treatment include symptomatic bacterial vaginosis, symptomatic vaginal candidiasis, trichomoniasis, chlamydia (CT), gonorrhea (GC), syphilis, active HSV lesions, chancroid, pelvic inflammatory disease, genital sores or ulcers, cervicitis, or symptomatic genital warts requiring treatment (i.e., those that cause undue burden or discomfort to the participant).
Note:
- An HSV-1 or HSV-2 seropositive diagnosis with no active lesions is allowed, since treatment is not required
- One re-screening after documented treatment will be allowed
Has any of the following laboratory abnormalities at Screening:
Note: Grade is per Version 2.1 of the DAIDS Toxicity Table
- Hemoglobin Grade 1 or higher
- Platelet count Grade 1 or higher
- International Normalized Ratio (INR) Grade 2 or higher
- White blood cell count Grade 2 or higher
- Calculated creatinine clearance ≤ 80 mL/minute using the Cockcroft-Gault equation
- Grade 2 or higher ALT and/or AST (i.e., ≥ 2.5x the site laboratory upper limit of normal [ULN])
- Positive for Hepatitis B surface antigen (HBsAg)
- Positive for Hepatitis C antibody (HCV Ab)
- Has any other condition that, in the opinion of the Principal Investigator or designee, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving study objectives
Male sexual partner(s) who meet the following criteria are not eligible for inclusion in the study:
1) Female partner did not utilize study product
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm 1
Arm 1 will receive the Tenofovir Disoproxil Fumarate (TDF)-Emtricitabine (FTC) pod-IVR for Stage 2 followed by the placebo pod-IVR during Stage 3.
|
TDF-FTC pod-IVR designed to deliver TDF at a target rate of 1 mg d-1 and FTC at a target rate of 2 mg d-1.
A placebo pod-IVR containing microcrystalline cellulose pods.
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Experimental: Arm 2
Arm 2 will receive the placebo pod-IVR for Stage 2 followed by the Tenofovir Disoproxil Fumarate (TDF)-Emtricitabine (FTC) pod-IVR during Stage 3.
|
TDF-FTC pod-IVR designed to deliver TDF at a target rate of 1 mg d-1 and FTC at a target rate of 2 mg d-1.
A placebo pod-IVR containing microcrystalline cellulose pods.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety of Vaginal IVRs releasing TDF-FTC by reports of Adverse Events
Time Frame: From date of enrollment until the date of study completion or date of study withdrawal from any cause, whichever came first, assessed up to 6 months
|
Adverse events Grade 2 or higher as defined by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1, March 2017, Addendum 1 Female Genital Grading Tables for Use in Microbicide Studies (November 2007), and/or Addendum 3 Rectal Grading Table for Use in Microbicide Studies (Clarification dated May 2012) to this table
|
From date of enrollment until the date of study completion or date of study withdrawal from any cause, whichever came first, assessed up to 6 months
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Characterization of pharmacokinetics of TDF-FTC released by an IVR - plasma
Time Frame: From date of enrollment until the date of study completion or date of study withdrawal from any cause, whichever came first, assessed up to 6 months
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To characterize the local and systemic pharmacokinetics (PK) of TDF-FTC delivered via a pod-IVR, including drug concentration in plasma.
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From date of enrollment until the date of study completion or date of study withdrawal from any cause, whichever came first, assessed up to 6 months
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Characterization of pharmacokinetics of TDF-FTC released by an IVR - vagina
Time Frame: From date of enrollment until the date of study completion or date of study withdrawal from any cause, whichever came first, assessed up to 6 months
|
To characterize the local and systemic pharmacokinetics (PK) of TDF-FTC delivered via a pod-IVR, including drug concentration in vaginal secretions and tissue.
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From date of enrollment until the date of study completion or date of study withdrawal from any cause, whichever came first, assessed up to 6 months
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Characterization of pharmacokinetics of TDF-FTC released by an IVR - rectum
Time Frame: From date of enrollment until the date of study completion or date of study withdrawal from any cause, whichever came first, assessed up to 6 months
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To characterize the local and systemic pharmacokinetics (PK) of TDF-FTC delivered via a pod-IVR, including drug concentration in rectal secretions.
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From date of enrollment until the date of study completion or date of study withdrawal from any cause, whichever came first, assessed up to 6 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Acceptability of IVR assessed via computer assisted self interviews
Time Frame: 28 days after use of each IVR
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Self-reported attitudes of participants about experience and product attributes via computer assisted self interviews
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28 days after use of each IVR
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Acceptability of IVR assessed via in depth interviews
Time Frame: 28 days after use of each IVR
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Self-reported attitudes of participants about experience and product attributes via in depth interviews
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28 days after use of each IVR
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Adherence
Time Frame: From date of IVR insertion until the date of IVR removal or date of study withdrawal from any cause, whichever came first, assessed up to 6 months
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Measured by vaginal fluid PK drug levels, vaginal tissue PK drug and drug metabolite levels, and residual drug levels in returned, used pod-IVRs.
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From date of IVR insertion until the date of IVR removal or date of study withdrawal from any cause, whichever came first, assessed up to 6 months
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Acceptability of IVR assessed via in depth interviews - male partners
Time Frame: 28 days after subject use of each IVR
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Self-reported attitudes of participant's male sexual partner(s) about experience and product attributes via in-depth interviews.
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28 days after subject use of each IVR
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Kathleen L Vincent, MD, University of Texas
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 17-0131
- 1U19AI113048-01 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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