Comparing on-demand PrEP formulations using rectal and oral tenofovir

A PHASE 2 CROSSOVER STUDY OF ON-DEMAND PREP FORMULATIONS COMPARING RECTAL AND ORAL TENOFOVIR-BASED PREP EVALUATING EXTENDED SAFETY, ACCEPTABILITY, AND PHARMACOKINETICS/PHARMACODYNAMICS

This study is testing two different ways of taking PrEP—one using a rectal douche and the other using oral pills—to see which method works better for preventing HIV in men who have anal sex.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 150 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Locations: 8 sites (Birmingham, Alabama and 7 other locations)
• Trial ID: NCT06560684 on ClinicalTrials.gov

What this trial studies

This Phase 2, multi-site, open-label randomized crossover study evaluates the safety, acceptability, adherence, and pharmacokinetics of two on-demand PrEP formulations: a rectal tenofovir douche followed by oral F/TDF pills, and vice versa. Participants will be randomized to one of the two sequences for an 8-week period, with a washout period of 2 to 4 weeks in between. The study aims to gather data on the effectiveness of these formulations in preventing HIV transmission among men assigned at birth who engage in receptive anal intercourse.

Who should consider this trial

Good fit: Ideal candidates for this study are men assigned at birth, aged 18 and older, who have a history of receptive anal intercourse and are willing to adhere to study protocols.

Not a fit: Patients who do not engage in receptive anal intercourse or those who are HIV positive will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide valuable insights into more effective PrEP options for HIV prevention.

How similar studies have performed: Other studies have explored various PrEP formulations, but this specific crossover approach comparing rectal and oral tenofovir is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Assigned male at birth

2.18 years of age or older at the time of screening informed consent

3.Willing and able to provide informed consent to take part in the study

4. Able to read at a level required for the study components (e.g., CASI and SMS)

5. Have access to device and the internet for completion of study procedures

6. Understand and agree to local STI reporting requirements

7.Non-reactive/negative HIV test results at screening and enrollment

8. A history of consensual RAI at least five times in their lifetime and at least once in the prior 3 months

9. Received or self-administered an enema or rectal douche more than half the time prior to engaging in RAI in the past year.

10. Willing and able to use condoms for all sexual intercourse for the duration of participation

11. 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

12. Willing and able to provide adequate locator information

13. Agrees not to knowingly engage in receptive or insertive sexual activity with another study participant for the duration of study participation.

14. Available to return for all study visits and within any site's catchment area

ADDITIONAL INCLUSION FOR THOSE IN THE PK/PD SUB-STUDY

1. Willing to refrain from occasional over-the-counter use of aspirin and NSAID use for 72 hours before and after each study biopsy visit
2. 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
3. Willing and able to use specific condoms and lubricant provided by the study clinic for all RAI for the duration of participation

Exclusion Criteria:

1. Any reactive/positive HIV test at screening or at least one reactive/positive test result at enrollment, even if HIV infection is not confirmed
2. History of active (including chronic) hepatitis B virus (HBV) infection, as documented by positive HBV surface antigen (HBsAg) at screening
3. 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).
4. ≥ Grade 2 laboratory abnormality at baseline as defined by The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 dated July 2017, except for estimated glomerular filtration rate (eGFR), which must be \>75 mL/ min. (Coagulation (PT/INR) results ≥ Grade 2 are not exclusionary for the main study).
5. 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)
6. 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.
7. History of an underlying clinically significant cardiac arrhythmia or renal disease
8. History of severe or recent cardiac or pulmonary event
9. History of significant gastrointestinal bleeding
10. 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
11. Use of injectable PrEP within 8 weeks prior to the screening visit or anticipated use throughout study participation
12. 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
13. Known allergic reaction to TFV or other components of the test articles
14. Current known partners with HIV, unless with sustained viral suppression on antiretroviral treatment (ART)
15. History of recurrent urticaria
16. Symptoms suggestive of acute HIV infection at screening or enrollment
17. 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

ADDITIONAL EXCLUSION FOR THOSE IN THE PK/PD SUB-STUDY

1. Current medically-indicated use of warfarin or heparin or other anticoagulant medications associated with increased risk for bleeding following mucosal biopsy (e.g., daily high dose aspirin \[\>81 mg\], non-steroidal anti-inflammatory drugs \[NSAIDs\], or Pradaxa®)
2. Previous use of injectable PrEP
3. ≥ Grade 2 laboratory result for coagulation testing (PT/INR) at baseline as defined by The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 dated July 2017.

Where this trial is running

Birmingham, Alabama and 7 other locations

• Alabama CRS (Site ID# 31788) — Birmingham, Alabama, United States (Not_yet_recruiting)
• UCLA CARE Center CRS — Los Angeles, California, United States (Not_yet_recruiting)
• Hope Clinic CRS — Lawrenceville, Georgia, United States (Not_yet_recruiting)
• Johns Hopkins University CRS — Baltimore, Maryland, United States (Recruiting)
• Fenway Health (FH) CRS — Boston, Massachusetts, United States (Not_yet_recruiting)
• Weill Cornell Chelsea CRS — New York, New York, United States (Not_yet_recruiting)
• Chapel Hill CRS (3201) — Chapel Hill, North Carolina, United States (Not_yet_recruiting)
• University of Pittsburgh CRS — Pittsburgh, Pennsylvania, United States (Recruiting)

Conditions Tenofovir; PrEP