Status:

NOT_YET_RECRUITING

PROTECT Study, "PRObiotics to TrEat Anal preCancer Trial

Lead Sponsor:

University of California, San Francisco

Collaborating Sponsors:

Exegi Pharma, LLC

National Cancer Institute (NCI)

Conditions:

HSIL, High Grade Squamous Intraepithelial Lesion

HPV-Related Squamous Cell Carcinoma

Eligibility:

All Genders

21+ years

Phase:

PHASE2

Brief 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 cance...

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 det...

Eligibility Criteria

Inclusion

  • Signed informed consent
  • Participant in ULACNet-101 or participant screened specifically for ULACNet-102.
  • Biopsy-proven anal HSIL (men or women) shown as part of participation in the ULACNet-101 study or at a screening visit for ULACNet-102.
  • At least one focus of anal HSIL must be large enough to be monitored for response, i.e.,not completely removed after the screening biopsy.
  • Total volume of HSIL is less than 50% of the anal canal or perianal region.
  • Must be actively on treatment with effective antiretroviral therapy (ART) regimen for at least three months preceding enrollment (Visit 1, Day 1) in ULACNet-101 or at screening for ULACNet-102.
  • HIV RNA \<200 copies/ml at baseline.
  • Cluster of differentiation 4 (CD4) nadir above 200 cells per microliter (uL)
  • Eastern Cooperative Oncology Group (ECOG) performance status \<=1 (Karnofsky \>= 70%).
  • Participants must meet the following laboratory parameters within 3 months before enrollment:
  • Leukocytes: ≥3,000/mm\^3.
  • Absolute neutrophil count: ≥1,500/mm\^3.
  • Platelets: ≥100,000/mm\^3.
  • Elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), or bilirubin \<2 times the upper limit of normal.
  • Not pregnant or breast feeding and one of the following:
  • Of non-childbearing potential (i.e. persons aged 60 years or older or who have had a hysterectomy or tubal ligation or are postmenopausal, as defined by no menses for at least 12 months and without an alternative medical cause).
  • Persons aged less than 60 years of childbearing potential and agree to practice highly effective contraception from initiation of taking EXE-346 or placebo through 14 days after taking the last dose of EXE-346 or placebo. Highly effective methods of contraception include one or more of the following:
  • i.Male partner who is sterile (medically effective vasectomy) prior to the female participant's entry into the study and is the sole sexual partner for the female participant.
  • ii.Hormonal (oral, intravaginal, transdermal, implantable or injectable); Progestogen-only hormonal contraceptives without inhibition of ovulation are not considered to be highly effective.
  • iii. An intrauterine hormone-releasing system. iv. An intrauterine device. v. Bilateral tubal occlusion or removal. vi. Sexual abstinence, only if the participant refrains from heterosexual intercourse from initiation taking EXE-346 or placebo through 14 days after taking the last dose of EXE-346 or placebo and it is the usual lifestyle of the participant.

Exclusion

  • History of any anogenital cancer.
  • Presence of untreated cervical HSIL or cervical cancer.
  • Anal HSIL on clinical examination or biopsy that clinicians are concerned for cancer.
  • Receipt of chemotherapy, radiotherapy or immunosuppressive medication in three months preceding enrollment in ULACNet-101 or at the screening visit for ULACNet-102.
  • Immunosuppression as a result of underlying illness or treatment including:
  • Use of high dose corticosteroids (\>10 mg/day prednisone or equivalent) for \>=7 days (inhaled, otic, topical and ophthalmic corticosteroids are permitted).
  • Primary immune deficiency disease.
  • Use of synthetic or biologic disease-modifying anti-rheumatic drugs.
  • History of bone marrow or solid organ transplant.
  • History of any other clinically significant autoimmune or immunosuppressive disease.
  • Participant initiated a new treatment with antibiotics within the 2 weeks prior to screening or plans to start antibiotic therapy during the study period.
  • Participant is taking NSAIDs as a long-term treatment (ie, consistent use for at least 4 days/week each month). Acute use of NSAIDs is allowed.
  • Participant has known hypersensitivity to EXE-346 or any product components.
  • Current known infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
  • Warts so extensive that they preclude the clinician from determining the extent and location of HSIL.
  • Sustained, manually confirmed, sitting systolic blood pressure \>150 mm Hg or \<90 mm Hg or a diastolic blood pressure \>95 mm Hg as measured by 3 readings taken 15 minutes apart at screening or Visit 1.
  • History of significant thrombocytopenia, history of thrombosis with thrombocytopenia (TTS) syndrome or heparin-induced thrombocytopenia.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
  • Participant has participated in any clinical study of an approved or unapproved investigational medicinal product within the 30 days prior to screening.
  • Any other finding that, in the opinion of the Investigator deems the participant unsuitable for the study

Key Trial Info

Start Date :

December 1 2025

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

October 31 2026

Estimated Enrollment :

90 Patients enrolled

Trial Details

Trial ID

NCT06949800

Start Date

December 1 2025

End Date

October 31 2026

Last Update

November 10 2025

Active Locations (2)

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Page 1 of 1 (2 locations)

1

Instituto Nacional de Cancerologia

Tlalpan, Mexico City, Mexico, 14080

2

University of Puerto Rico Comprehensive Cancer Center

San Juan, Puerto Rico, 00936