Tenofovir Rectal Douche to Prevent HIV Transmission

NCT04016233 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: IRB001963105U19AI113127
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

HIV/AIDS; HIV Prevention

Keywords

Tenofovir; Tenofovir douche

Outcome Measures

Primary Outcomes (5)

• Change in Tenofovir Diphosphate (TFV-DP) concentration

  Colonic tissue cell TFV-DP concentrations (femtomoles/million cells) will be measured after each study douche sequence administration, based on the individual participant's sampling schedule, on Day 1 (at 1 hour, 3 hours, or 6 hours post dose), Day 2 (24 hours post dose), Day 4 (72 hours post dose), or Day 8 (168 hours post dose).

  At 1 hour, 3 hours, 6 hours, 24 hours, 72 hours, 168 hours after each TFV douche sequence administration

• Acceptability of TFV Douche Sequence A as assessed by Sequence A Acceptability Questionnaire

  To analyze study product sequence acceptability, the outcome will be examined in both continuous and dichotomous forms. For each sequence, descriptive statistics of overall acceptability will be generated (i.e., mean and standard deviation for continuous variables and proportion of subjects who consider the sequences acceptable -- with score 3 or greater). The acceptability of each sequence is defined as a mean score of 3 on 4-point continuous acceptability measure (1=completely unacceptable; 2=somewhat unacceptable; 3=somewhat acceptable; 4=highly acceptable) that is defined in this study as the minimal clinically meaningful threshold for sequence acceptability. Each sequence acceptability questionnaire consists of 6 sections with 36 questions total.

  Following administration of study product sequence A, up to 1 hour

• Acceptability of TFV Douche Sequence B as assessed by Sequence B Acceptability Questionnaire

  To analyze study product sequence acceptability, the outcome will be examined in both continuous and dichotomous forms. For each sequence, descriptive statistics of overall acceptability will be generated (i.e., mean and standard deviation for continuous variables and proportion of subjects who consider the sequences acceptable -- with score 3 or greater). The acceptability of each sequence is defined as a mean score of 3 on 4-point continuous acceptability measure (1=completely unacceptable; 2=somewhat unacceptable; 3=somewhat acceptable; 4=highly acceptable) that is defined in this study as the minimal clinically meaningful threshold for sequence acceptability. Each sequence acceptability questionnaire consists of 6 sections with 36 questions total.

  Following administration of study product sequence B, up to 1 hour

• Acceptability of TFV Douche Sequence C as assessed by Sequence C Acceptability Questionnaire

  To analyze study product sequence acceptability, the outcome will be examined in both continuous and dichotomous forms. For each sequence, descriptive statistics of overall acceptability will be generated (i.e., mean and standard deviation for continuous variables and proportion of subjects who consider the sequences acceptable -- with score 3 or greater). The acceptability of each sequence is defined as a mean score of 3 on 4-point continuous acceptability measure (1=completely unacceptable; 2=somewhat unacceptable; 3=somewhat acceptable; 4=highly acceptable) that is defined in this study as the minimal clinically meaningful threshold for sequence acceptability. Each sequence acceptability questionnaire consists of 6 sections with 36 questions total.

  Following administration of study product sequence C, up to 1 hour

• Change in participant behavior from baseline and study product desirability as assessed by In-Depth Interview

  A final In-depth Interview will be conducted over the telephone by a trained interviewer. This interview will explore associations between baseline behavior, experience using the products during the study, and likelihood of product use in the future. This interview will take place at the final clinic visit after all behavioral assessments have been completed.

  Upon completion of the study at final visit, up to 2 hours

Study Arms (1)

Three TFV Medicated Douche Sequences

EXPERIMENTAL

Once enrolled, participants will complete a baseline sampling session and then three sequences of study product administration, each with 3 douches. Sequence A will be 3 sequential doses of TFV douche; Sequence B will be one dose of TFV douche followed by 2 sequential non-medicated douches; Sequence C will be 2 sequential non-medicated douches followed by a single dose of TFV douche. There will be a washout period of at least 14 days between sequences. Participants will have sequences administered in clinic or a research unit, followed by various specimen collections over 8 days according to individual sampling schedule assigned to each participant. Specimens will be collected on Days 1, 2, 4, and 8 post sequence administration.

Drug: Tenofovir douche

Interventions

Tenofovir douche DRUG

660 mg TFV in 125 mL hypo-osmolar solution

Three TFV Medicated Douche Sequences

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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)
• 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.

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• University of Pittsburgh: collaborator

Study Sites (2)

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Craig Hendrix, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2019
• First Posted: July 11, 2019
• Study Start: January 10, 2020
• Primary Completion: April 27, 2021
• Study Completion: April 27, 2021
• Last Updated: June 9, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)