Evaluating Distribution of a Tenofovir Douche With Tap Water Douching and Simulated Receptive Anal Intercourse

NCT04195776 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: IRB002083381U19AI113127
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

DREAM-02 is a phase 1, open label study to evaluate different sequences of tap water douching and simulated receptive anal intercourse (sRAI) in the presence of a tenofovir douche designed to confer protection from Human Immunodeficiency Virus (HIV) acquisition. DREAM-02 will assess the safety and pharmacokinetics (PK) of different sequences of administration of tap water (H2O) and rectal tenofovir (TFV) douches to more accurately represent the community practice of commonly using cleansing douches prior to RAI, and occasionally after RAI. DREAM-02 results are essential to gain understanding of Tenofovir diphosphate (TFV-DP) concentrations at various anatomic distances in the colon, and how those concentrations may be modified by sRAI, seminal fluid, and sequence of cleansing tap water douches.

Conditions

HIV/AIDS; HIV Prevention

Keywords

Tenofovir; Tenofovir douche

Outcome Measures

Primary Outcomes (1)

• Change in Tenofovir Diphosphate (TFV-DP) concentration

  Colonic tissue cell TFV-DP concentrations (femtomoles/million cells) will be measured 3 hours after each study douche sequence administration.

  Approximately 6 months from the time of enrollment

Secondary Outcomes (1)

• Anatomic distribution of radiolabeled Tenofovir douche

  Approximately 6 months from the time of enrollment

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, along with sRAI and administration of autologous seminal fluid. Sequence A will be 1 TFV douche followed by sRAI; Sequence B will be one dose of TFV douche followed sRAI then a tap water douche; Sequence C will be 1 tap water douche followed sRAI then 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 imaging and various specimen collections over 8 hours.

Drug: Tenofovir Douche

Interventions

Tenofovir Douche DRUG

660 mg TFV in 125 mL hypo-osmolar solution

Also known as: TFV 660 mg in hypo-osmolar solution

Three TFV Medicated Douche Sequences

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: This study will include individuals biologically assigned male gender at birth.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Biologically assigned male gender at birth, 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
• 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
• Willing to provide a semen sample on multiple occasions
• Wiling to perform simulated RAI with the Coital Dynamic Simulation (CDS) device
• Available to return for all study visits, barring unforeseen circumstances
• Per participant report at screening, a history of consensual RAI
• Per participant report at screening, experience with receiving or self-administering a rectal douche in the context of RAI.
• If the study participant is currently prescribed oral TDF 300 mg/emtricitabine (FTC) 200 mg (Truvada®), or FTC 200 mg/tenofovir alafenamide (TAF) 25 mg (Descovy®) as HIV Pre Exposure Prophylaxis (PrEP), the participant may continue to take oral PrEP as prescribed as long as the participant agrees to adhere to a consistent dosing schedule throughout the study duration.
• 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 ejaculation for a period of 48 hours prior to each semen collection
• Willing to refrain from high daily dose aspirin (\>81 mg) and NSAID use for one week before and after each study biopsy visit

You may not qualify if:

• History of chronic 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)
• Serum phosphate \<2.3 mg/dL
• 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 external 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)
• 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 partners, or if in the opinion of the investigator, the participant identifies as a commercial sex worker, or has frequent unprotected RAI with partners of unknown HIV status.
• Use of injection or non-injections drugs that in the opinion of the investigator could compromise participant safety or the integrity of the study.
• Symptoms suggestive of acute HIV seroconversion at screening and enrollment
• Participants whose whole body (ED) radiation exposure, per participant report, exceeds 5000 mrem/year
• 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.

Sponsors & Collaborators

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

Study Sites (1)

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Related Publications (1)

• Zheng R, Fuchs EJ, Nimmagadda S, Rohan LC, Wang L, Bertagnolli LN, Massih S, Caffo BS, Hendrix CW. Anal Sex and Tenofovir Douche Sequence Impacts Colorectal Distribution of HIV Surrogate and Douche: DREAM-02. J Infect Dis. 2025 Sep 15;232(3):588-595. doi: 10.1093/infdis/jiaf286.

  PMID: 40447283 DERIVED

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

• Sridhar Nimmagadda, PhD

  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: December 10, 2019
• First Posted: December 12, 2019
• Study Start: June 1, 2021
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: January 17, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)