Tenofovir Rectal Douche to Prevent HIV Transmission

• Status: Completed
• Trial end date: 2021-04-27
• Target enrollment: 0
• Participant gender: All

Summary

DREAM-03 is an early phase-1, open label study to compare the safety, pharmacokinetics (PK), pharmacodynamics (PD), and acceptability of 3 sequences of tenofovir (TFV) and non-medicated douches. The overall goal is to inform the design of an extended safety study of an on-demand and behaviorally congruent TFV douche to confer protection from HIV acquisition in an outpatient pre-RAI context.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Johns Hopkins University
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); University of Pittsburgh
• Treatments: Tenofovir

Criteria

Inclusion Criteria:

• 18 years of age or older at screening

• Willing and able to communicate in English

• Willing and able to provide written informed consent to take part in the study; non-literate individuals may indicate consent with a thumbprint accompanied by the signature of an objective witness

• Willing and able to provide adequate locator information

• Understand and agree to local Sexually Transmitted Infection (STI) reporting requirements

• HIV-1 uninfected at screening as documented by Combo Ag/Ab HIV-1/HIV-2 immunoassay (refer to Appendix II for confirmatory testing algorithm)

• Available to return for all study visits, barring unforeseen circumstances

• Per participant report at screening, a history of consensual Receptive Anal Intercourse (RAI) at least five times in lifetime

• Per participant report at screening, experience with receiving or self-administering multiple rectal douches in the context of RAI in the past year.

• If the study participant is currently prescribed oral Tenofovir Disoproxil Fumarate (TDF) 300 mg/Emtricitabine (FTC) 200 mg (TruvadaTM) as HIV Pre-Exposure Prophylaxis (PrEP), the participant may continue to take oral TDF/FTC as prescribed as long as the participant agrees to adhere to a consistent dosing schedule throughout the study duration.

• If of reproductive potential (defined as pre-menopausal cisgender women or transgender men who have not had a sterilization procedure per self-report, such as hysterectomy, bilateral oophorectomy, tubal ligation or salpingectomy), must have a negative beta human chorionic gonadotropin (βHCG) pregnancy test (sensitivity of ≤ 25 milli-international units per milliliter (mIU/mL)) performed (and results known) on the same day as and before initiating the protocol-specified study product at Visit 3.

• If of reproductive potential, women must agree to use a reliable form of contraception, during the trial and for 4 weeks after the final study product doses, from the list below:

1. Intrauterine device (IUD) or intrauterine system (IUS) that meets <1% failure rate as stated in the product label.

2. Hormone-based contraceptive that meets <1% failure rate as stated in the product label

• Willing to abstain from insertion of anything (drug/medication, penis, object, sex toy, or douche) into the anorectum for 72 hours before and after each research unit study product exposure and 7 days after each flexible sigmoidoscopy with biopsy collection.

• Willing to refrain from aspirin and Nonsteroidal anti-inflammatory drug (NSAID) use for one week before and after each study biopsy visit

• Willing and able to use condoms provided by the study for all RAI for the duration of participation

• Agrees not to participate in other research studies involving drugs and/ or medical devices for the duration of the study

Exclusion Criteria:

• History of Hepatitis B infection, as documented by positive HBsAg at screening

• ≥ Grade 2 laboratory abnormality at baseline as defined by Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 - July 2017, and Addendum 3 (Rectal Grading Tables for Use in Microbicide Studies)

• Significant colorectal symptom(s) as determined by medical history or by participant self-report (including but not limited to presence of any unresolved injury, infectious or inflammatory condition of the local mucosa, history of inflammatory bowel disease, presence of symptomatic hemorrhoids, and presence of any painful anorectal conditions that would be tender to manipulation)

• At screening or within the past 2 months: participant-reported symptoms and/or clinical or laboratory diagnosis of active rectal or reproductive tract infection requiring treatment per current Centers for Disease Control and Prevention (CDC) guidelines or symptomatic urinary tract infection (UTI). Infections requiring treatment include Chlamydia (CT), gonorrhea (GC), syphilis, active Herpes Simplex Virus (HSV) lesions, chancroid, genital sores or ulcers, and, if clinically indicated, genital warts. Note that HSV seropositivity with no active genital lesions is not an exclusion criterion. (Note: if an STI apart from HIV is detected, the participant will be referred for treatment and can be retested in 30 days and rescreened once.)

• History of an underlying clinically significant cardiac arrhythmia or renal disease (including creatinine clearance <60 mL/min using Cockcroft-Gault equation)

• Serum phosphate < 2.3 mg/dL

• History of severe or recent cardiac or pulmonary event

• History of significant gastrointestinal bleeding

• Current use of warfarin or heparin or other anticoagulant medications associated with increased risk for bleeding following mucosal biopsy (e.g., daily high dose aspirin [>81 mg], NSAIDs, or Pradaxa®)

• Use of systemic or anorectal immunomodulatory medications within 4 weeks of enrollment or planned use at any time during study participation

• Per participant report, use of any rectally administered products containing N-9 (including condoms) or investigational products within 4 weeks of enrollment, or planned use of either at any time during study participation

• Known allergic reaction to TFV or other components of the test articles

• Current known HIV-infected partner(s)

• History of recurrent urticaria

• Symptoms suggestive of acute HIV seroconversion at screening and enrollment

• Any other condition or prior therapy that, in the opinion of the investigator, would preclude informed consent, make study participation unsafe, make the individual unsuitable for the study or unable to comply with the study requirements. Such conditions may include, but are not limited to, current or recent history of severe, progressive, or uncontrolled substance abuse, or renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, or cerebral disease.