CROSSOVER STUDY OF ON-DEMAND PREP FORMULATIONS COMPARING RECTAL AND ORAL TENOFOVIR

NCT06560684 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HPTN 106
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 8

Brief Summary

This is a Phase 2, multi-site, two-period, open label randomized crossover (Period 1 and 2) study. Participants are randomized 1:1 to one of two 8-week on-demand product sequences - TFV douche then oral F/TDF or oral F/TDF then TFV douche - with a 2 to 4-week washout period in between. Domains of safety, acceptability, adherence, and PK/PD (sub-study only) are assessed for each product.

Conditions

Tenofovir

Keywords

PrEP

Outcome Measures

Primary Outcomes (3)

• Grade 2 or higher adverse events during each study Period

  For eGFR, participants may enroll in the study with an eGFR value consistent with a grade 2 adverse event; thus, an exception will be made for eGFR, which will be considered a safety outcome if it worsens to a grade 3 or higher.

  Week 1 through 19

• Any adverse event leading to study product discontinuation during each study Period

  Week 1 through 19

• Self-report on ease of use, product liking, and likelihood of future use during each study Period

  measured via computer-assisted self-interview (CASI), with the scales for the specific questions ranging from 1 (lowest ranking) to 4 (highest ranking).

  Week 1 through 19

Secondary Outcomes (4)

• Proportion of participants who reported being most likely to use the TFV douche in the future (following Period 2)

  Week 1 through 19

• Percent prescribed weekly doses taken in each Period using multiple subjective and objective measures

  Week 1 through 19

• TFV and FTC concentrations in blood plasma and rectal tissue biopsies

  Week 1 through 19

• TFV-DP and FTC-TP concentrations in PBMCs, rectal tissue biopsies, and mucosal mononuclear cells (MMC)

  Week 1 through 19

Study Arms (2)

Group A

EXPERIMENTAL

Those participants assigned to Group A will start with the rectal TFV 660 mg douche for the first 8 weeks (Period 1) and then after a 2-4 week washout will switch to the on-demand oral F/TDF 200 mg/300 mg sequence for the next 8 weeks (Period 2).

Drug: Oral F/TDF Pills; Drug: TFV rectal douche

Group B

EXPERIMENTAL

Those participants assigned to Group B will start with the on-demand oral F/TDF 200 mg/300 mg sequence for 8 weeks and then after a 2-4 week washout will switch to the rectal TFV 660 mg douche for the next 8 weeks (Period 2).

Drug: Oral F/TDF Pills; Drug: TFV rectal douche

Interventions

Oral F/TDF Pills DRUG

For 8 weeks of each study period, the participant will take the study product at least weekly prior to anticipated RAI.

Group A; Group B

TFV rectal douche DRUG

For 8 weeks of each study period, the participant will take the study product at least weekly prior to anticipated rectal anal intercourse (RAI).

Group A; Group B

Eligibility Criteria

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

You may qualify if:

• Men aged 18 years or older at the time of screening informed consent
• Willing and able to provide informed consent to take part in the study
• Able to read at a level required for the study components (e.g., CASI and SMS)
• Have access to device and the internet for completion of study procedures
• Understand and agree to local STI reporting requirements
• Non-reactive/negative HIV test results at screening and enrollment
• A history of consensual RAI at least five times in their lifetime and at least once in the prior 3 months
• Received or self-administered an enema or rectal douche more than half the time prior to engaging in RAI in the past year.
• Willing and able to use condoms for all sexual intercourse for the duration of participation
• Agrees not to participate in other research studies involving drugs, biologics, medical devices, vaccines, anal products, or genital products for the duration of the study
• Willing and able to provide adequate locator information
• Agrees not to knowingly engage in receptive or insertive sexual activity with another study participant for the duration of study participation.
• Available to return for all study visits and within any site's catchment area
• Willing to refrain from occasional over-the-counter use of aspirin and NSAID use for 72 hours before and after each study biopsy visit
• Willing to abstain from insertion of anything (e.g., drug/medication, penis, object, sex toy, or enema including take-home enema) into the anorectum for 72 hours before study drug dose and until 72 hours after each flexible sigmoidoscopy with biopsy collection, or one week after the study drug dose, whichever is later

You may not qualify if:

• Any reactive/positive HIV test at screening or at least one reactive/positive test result at enrollment, even if HIV infection is not confirmed
• History of active (including chronic) hepatitis B virus (HBV) infection, as documented by positive HBV surface antigen (HBsAg) at screening
• Co-enrollment in any other interventional research study that may interfere with this study (as provided by self-report or other available documentation). Exceptions may be made after consultation with the Clinical Management Committee (CMC).
• 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)
• 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)
• a.Infections requiring treatment include chlamydia (CT), gonorrhea (GC), syphilis, active HSV lesions, chancroid, genital sores or ulcers, and, if clinically indicated, genital warts.
• Note: if an STI apart from HIV is detected, the participant will be referred for treatment and, upon documented confirmation of definitive treatment, can be retested in three weeks for evidence of adequate treatment.
• History of an underlying clinically significant cardiac arrhythmia or renal disease
• History of severe or recent cardiac or pulmonary event
• History of significant gastrointestinal bleeding
• Use of F/TDF or use of F/TAF as HIV PrEP within 8 weeks prior to screening visit or anticipated use throughout study participation
• Use of injectable PrEP within 8 weeks prior to the screening visit or anticipated use throughout study participation
• Use of systemic or anorectal immunomodulatory medications, rectally administered products containing N-9 or corticosteroids, or any investigational products unless otherwise permitted within 4 weeks of screening or planned use at any time during study participation
• Known allergic reaction to TFV or other components of the test articles
• Current known partners with HIV, unless with sustained viral suppression on antiretroviral treatment (ART)

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (8)

Alabama CRS (Site ID# 31788)

Birmingham, Alabama, 35222, United States

Location

UCLA CARE Center CRS

Los Angeles, California, 90035, United States

Location

Hope Clinic CRS

Lawrenceville, Georgia, 30046, United States

Location

Johns Hopkins University CRS

Baltimore, Maryland, 21287, United States

Location

Fenway Health (FH) CRS

Boston, Massachusetts, 02215-4302, United States

Location

Weill Cornell Chelsea CRS

New York, New York, 10011, United States

Location

Chapel Hill CRS (3201)

Chapel Hill, North Carolina, 27599-7215, United States

Location

University of Pittsburgh CRS

Pittsburgh, Pennsylvania, 15213, United States

Location

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2024
• First Posted: August 19, 2024
• Study Start: October 29, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)