NCT06949800

CASCADE 2002: PROTECT Study, "PRObiotics to TrEat Anal preCancer Trial

Probiotics to Treat HSIL and Reduce Persistent High Risk HPV Infection in Women and Men Living With HIV

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 90 (estimated)
• Sponsor: University of California, San Francisco · Academic / Other
• Sex: All
• Age: 21 Years
• Healthy volunteers: Not accepted

Summary

This study is focused on treatment of anal high-grade squamous intraepithelial lesions (HSIL) in persons with HIV (PWH), with the ultimate goal of applying the approach toward prevention of anal cancer in this population

Detailed description

This is a randomized double-blinded, placebo-controlled trial. PRIMARY OBJECTIVES: I. Evaluate regression to no disease among people with HIV (PWH) with anal HSIL at baseline at Week 36. II. To determine the safety of EXE-346 in PWH. SECONDARY OBJECTIVES: I. To evaluate regression to LSIL or normal at Week 36 among PWH with anal HSIL at baseline. II. To evaluate clearance at Week 36 to HPV-negative in anal swab for type(s) found at the baseline visit in PWH. EXPLORATORY OBJECTIVES: I. To determine if changes in the microbiome from baseline to Week 36 correlate with regression of anal HSIL to low grade squamous intraepithelial lesions (LSIL) or normal, or clearance of HPV found at baseline. Participants will be randomized in a block design used to stratify women or men according to high-risk human papillomavirus (hrHPV) status (HPV16 present or absent in baseline swab). After confirmation of biopsy-proven HSIL, participants will receive sachets of EXE-346 or placebo for up to 3 months (12 weeks) with follow-up visits at 24 weeks and 36 weeks. Participants with HSIL at week 36 may be treated with non-investigational, standard of care, hyfrecation.

Conditions

• HSIL, High Grade Squamous Intraepithelial Lesion
• HPV-Related Squamous Cell Carcinoma
• Anal HSIL

Interventions

Type	Name	Description
DRUG	EXE-346 Probiotic	Given as a single-dose, powder packet to mix with water
DRUG	Placebo	Given as a single-dose, powder packet to mix with water
PROCEDURE	Usual Care High Resolution Anoscopy (HRA)	Non-investigational HRA will be performed

Timeline

• Start date: 2026-03-15
• Primary completion: 2026-12-31
• Completion: 2026-12-31
• First posted: 2025-04-29
• Last updated: 2026-02-02

Locations

2 sites across 2 countries: United States, Puerto Rico

Regulatory

• FDA-regulated drug study