PrEP-Pod-IVR (TDF-FTC/Placebo IVR 28 Day Crossover Study)

NCT03255915 | Unknown Early Phase 1 FDA Drug

• 2 other identifiers: 17-01311U19AI113048-01
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Participants will have a 28-day pre-ring baseline assessment period (Stage 1) followed by randomization to order with 5 participants per study arm. All participants will sequentially receive both study products for 28-days with at least a 2-week washout period between products. Arm 1 will receive the TDF-FTC pod-IVR for Stage 2 followed by the placebo pod-IVR during Stage 3. Arm 2 will receive the placebo pod-IVR for Stage 2 followed by the TDF-FTC pod-IVR during Stage 3. During Stages 2 \& 3 participants will also complete brief phone surveys (\<3 min), computer-assisted self-interviews (CASIs), and in-depth interviews (IDIs) regarding perceptibility and acceptability. If willing, participants' male sexual partners will be invited to complete IDIs as well.

Conditions

HIV Prevention

Keywords

HIV Prevention; Intravaginal Ring; Tenofovir Disoproxil Fumarate; Emtricitabine

Outcome Measures

Primary Outcomes (4)

• Safety of Vaginal IVRs releasing TDF-FTC by reports of Adverse Events

  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

• Characterization of pharmacokinetics of TDF-FTC released by an IVR - plasma

  To characterize the local and systemic pharmacokinetics (PK) of TDF-FTC delivered via a pod-IVR, including drug concentration in plasma.

  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

• Characterization of pharmacokinetics of TDF-FTC released by an IVR - vagina

  To characterize the local and systemic pharmacokinetics (PK) of TDF-FTC delivered via a pod-IVR, including drug concentration in vaginal secretions and tissue.

  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

• Characterization of pharmacokinetics of TDF-FTC released by an IVR - rectum

  To characterize the local and systemic pharmacokinetics (PK) of TDF-FTC delivered via a pod-IVR, including drug concentration in rectal secretions.

  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 Outcomes (4)

• Acceptability of IVR assessed via computer assisted self interviews

  28 days after use of each IVR

• Acceptability of IVR assessed via in depth interviews

  28 days after use of each IVR

• Adherence

  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

• Acceptability of IVR assessed via in depth interviews - male partners

  28 days after subject use of each IVR

Study Arms (2)

Arm 1

EXPERIMENTAL

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.

Drug: Tenofovir Disoproxil Fumarate (TDF)-Emtricitabine (FTC); Other: Placebo

Arm 2

EXPERIMENTAL

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.

Drug: Tenofovir Disoproxil Fumarate (TDF)-Emtricitabine (FTC); Other: Placebo

Interventions

Tenofovir Disoproxil Fumarate (TDF)-Emtricitabine (FTC) DRUG

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.

Arm 1; Arm 2

Placebo OTHER

A placebo pod-IVR containing microcrystalline cellulose pods.

Arm 1; Arm 2

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Oak Crest Institute of Science: lead
• The Miriam Hospital: collaborator
• Johns Hopkins University: collaborator
• University of California, Los Angeles: collaborator
• University of California, San Diego: collaborator
• Vanderbilt University: collaborator
• The University of Texas Medical Branch, Galveston: collaborator
• National Institutes of Health (NIH): collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

University of Texas Medical Branch

Galveston, Texas, 77555, United States

Location

MeSH Terms

Interventions

Tenofovir

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Kathleen L Vincent, MD

  University of Texas

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized order, placebo-controlled, double blind, crossover

Study Record Dates

• First Submitted: July 26, 2017
• First Posted: August 21, 2017
• Study Start: September 20, 2018
• Primary Completion: September 30, 2020
• Study Completion: December 31, 2025
• Last Updated: November 3, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)