HSIL, High Grade Squamous Intraepithelial LesionPhase 2NCT06949800
CASCADE 2002: PROTECT Study, "PRObiotics to TrEat Anal preCancer Trial
A Phase 2 study testing EXE-346 Probiotic in people with HSIL, High Grade Squamous Intraepithelial Lesion and HPV-Related Squamous Cell Carcinoma, run by University of California, San Francisco at 2 sites in 2 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- HSIL, High Grade Squamous Intraepithelial Lesion, HPV-Related Squamous Cell Carcinoma, Anal HSIL
- What is being tested?
- EXE-346 Probiotic
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 4 Sep 2026to 31 May 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent
- Biopsy-proven anal HSIL (men or women) at a screening visit for C2002, or clinic patients with known untreated HSIL diagnosed within the previous 3 months.
- 4. 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.
- 5. Total volume of HSIL is less than 50% of the anal canal or perianal region. 6.Must be actively on treatment with effective antiretroviral therapy (ART) regimen for at least three months preceding enrollment (Visit 1, Day 1) at screening for C2002.
- 7.HIV RNA <200 copies/ml at baseline. 9.Eastern Cooperative Oncology Group (ECOG) performance status <=1 (Karnofsky >= 70%).
- 10. Participants must meet the following laboratory parameters within 3 months before enrollment:
Show all 13Show fewer
- Leukocytes: ≥3,000/mm^3. b. Absolute neutrophil count: ≥1,500/mm^3. c. Platelets: ≥100,000/mm^3. d. Elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), or bilirubin <=2 times the upper limit of normal.
- 11. 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.
- 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.
Who cannot join
- History of any anogenital cancer.
- History of inflammatory bowel disease
- 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:
Show all 22Show fewer
- 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.
- Use of probiotics other than EXE-346 during the study and for a period of two weeks prior to screening.
- 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.
Trial locations and contacts
2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
2 sites in 2 countries
United States1 site, 1 recruiting
- Recruiting
University of California, San Francisco
San Francisco, California, 94143
Ross Jamison, (415) 353-9042, Ross.Jamison@ucsf.edu
877-827-3222, cancertrials@ucsf.edu
Puerto Rico1 site, 1 recruiting
- Not yet recruiting
University of Puerto Rico Comprehensive Cancer Center
San Juan, Puerto Rico, 00936
Ana Patricia Ortiz Martinez, MPH, MD
About this study
Official title: Probiotics to Treat HSIL and Reduce Persistent High Risk HPV Infection in Women and Men Living With HIV
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
Read the detailed description
This is a randomized double-blinded, placebo-controlled trial.
PRIMARY OBJECTIVES:
- 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:
- 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:
- 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
- Being tested
- EXE-346 Probiotic, Placebo, Usual Care High Resolution Anoscopy (HRA)
- Keywords
- HIV, Anal intraepithelial neoplasia (AIN) 3, p16+ AIN 2
- Medical subject headings
- Squamous Intraepithelial Lesions
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EXE-346 ProbioticDrug
Also called EXE-346 Probiotic formula, Probiotic
Given as a single-dose, powder packet to mix with water
PlaceboDrug
Also called Blinded Placebo
Given as a single-dose, powder packet to mix with water
Usual Care High Resolution Anoscopy (HRA)Procedure or surgery
Also called HRA
Non-investigational HRA will be performed
| Study group | Role | What they receive |
|---|---|---|
| Blinded: EXE-346 probiotic | Experimental | Participants will be blinded and stratified on gender and according to hrHPV status (HPV16 present or absent in baseline swab). After confirmation of biopsy-proven HSIL, participants will receive sachets of EXE-346 or placebo, with the contents suspended in water and consumed orally twice per day for 3 months (12 weeks) with follow-up visits at 24 and 36 weeks. Participants will undergo High resolution anoscopy (HRA) as a safety check at Visit 3 (12 weeks) and at Visit 4 (24 weeks) to ensure HRA has not progressed to cancer. Biopsies will only be performed if there is any concern for progression. Participants with active HSIL at week 36 will be treated with non-investigational, standard of care, hyfrecation as soon as possible, but within 8 weeks. Receives: Drug: EXE-346 Probiotic; Procedure: Usual Care High Resolution Anoscopy (HRA) |
| Blinded: Placebo | Placebo comparator | Participants will be blinded and stratified on gender and according to hrHPV status (HPV16 present or absent in baseline swab). After confirmation of biopsy-proven HSIL, participants will receive sachets of EXE-346 or placebo, with the contents suspended in water and consumed orally twice per day for 3 months (12 weeks) with follow-up visits at 24 and 36 weeks. Participants will undergo High resolution anoscopy (HRA) as a safety check at Visit 3 (12 weeks) and at Visit 4 (24 weeks) to ensure HRA has not progressed to cancer. Biopsies will only be performed if there is any concern for progression. Participants with active HSIL at week 36 will be treated with non-investigational, standard of care, hyfrecation as soon as possible, but within 8 weeks. Receives: Drug: Placebo; Procedure: Usual Care High Resolution Anoscopy (HRA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of participants with no disease present
No anal disease defined as complete regression of lesions as determined by examination of biopsies obtained at HRA
Measured: Up to 36 weeks
Proportion of participants reporting treatment-emergent adverse events
The frequency of participants reporting adverse events by group will be classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0
Measured: Up to 36 weeks
Secondary outcomes (2)
Proportion of participants with demonstrated disease regression
Regression of HSIL associated with any hrHPV type to LSIL or lower, as determined by examination of biopsies obtained at HRA
Measured: Up to 36 weeks
Proportion of participants with HPV-negative status
The proportion of participants with HPV-negative on anal swab for type(s) found at baseline will be reported.
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2025
- Study start4 Sep 2026
- Primary completion31 Oct 2027 (estimated)
- Study completion31 May 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HSIL, High Grade Squamous Intraepithelial LesionStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Exegi Pharma, LLC, National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Joel Palefsky, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06949800
- Sponsor's protocol ID
- 25361
- Other IDs
- U24CA275417
- Status last verified
- Oct 2026
- First submitted
- 22 Apr 2025
- Last updated
- 29 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified information will be shared with study collaborators
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Probiotics to Treat HSIL and Reduce Persistent High Risk HPV Infection in Women and Men Living With HIV
- ClinicalTrials.gov ID
- NCT06949800
- Acronym / sponsor ID
- 25361
- Conditions
- HSIL, High Grade Squamous Intraepithelial Lesion, HPV-Related Squamous Cell Carcinoma, Anal HSIL
- Keywords
- HIV, Anal intraepithelial neoplasia (AIN) 3, p16+ AIN 2
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Exegi Pharma, LLC, National Cancer Institute (NCI)
- Study start
- 4 Sep 2026 (actual)
- Primary completion
- 31 Oct 2027 (estimated)
- Study completion
- 31 May 2028 (estimated)
- First posted
- 29 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Blinded: EXE-346 probiotic | Experimental | Drug: EXE-346 Probiotic, Procedure: Usual Care High Resolution Anoscopy (HRA)Participants will be blinded and stratified on gender and according to hrHPV status (HPV16 present or absent in baseline swab). After confirmation of biopsy-proven HSIL, participants will receive sachets of EXE-346 or placebo, with the contents suspended in water and consumed orally twice per day for 3 months (12 weeks) with follow-up visits at 24 and 36 weeks. Participants will undergo High resolution anoscopy (HRA) as a safety check at Visit 3 (12 weeks) and at Visit 4 (24 weeks) to ensure HRA has not progressed to cancer. Biopsies will only be performed if there is any concern for progression. Participants with active HSIL at week 36 will be treated with non-investigational, standard of care, hyfrecation as soon as possible, but within 8 weeks. |
| Blinded: Placebo | Placebo comparator | Drug: Placebo, Procedure: Usual Care High Resolution Anoscopy (HRA)Participants will be blinded and stratified on gender and according to hrHPV status (HPV16 present or absent in baseline swab). After confirmation of biopsy-proven HSIL, participants will receive sachets of EXE-346 or placebo, with the contents suspended in water and consumed orally twice per day for 3 months (12 weeks) with follow-up visits at 24 and 36 weeks. Participants will undergo High resolution anoscopy (HRA) as a safety check at Visit 3 (12 weeks) and at Visit 4 (24 weeks) to ensure HRA has not progressed to cancer. Biopsies will only be performed if there is any concern for progression. Participants with active HSIL at week 36 will be treated with non-investigational, standard of care, hyfrecation as soon as possible, but within 8 weeks. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Signed informed consent
- Biopsy-proven anal HSIL (men or women) at a screening visit for C2002, or clinic patients with known untreated HSIL diagnosed within the previous 3 months.
- 4. 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.
- 5. Total volume of HSIL is less than 50% of the anal canal or perianal region. 6.Must be actively on treatment with effective antiretroviral therapy (ART) regimen for at least three months preceding enrollment (Visit 1, Day 1) at screening for C2002.
- 7.HIV RNA <200 copies/ml at baseline. 9.Eastern Cooperative Oncology Group (ECOG) performance status <=1 (Karnofsky >= 70%).
Key exclusion criteria (22 listed)
- History of any anogenital cancer.
- History of inflammatory bowel disease
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EXE-346 ProbioticAlso: EXE-346 Probiotic formula, ProbioticGiven as a single-dose, powder packet to mix with water | Drug | Blinded: EXE-346 probiotic |
| PlaceboAlso: Blinded PlaceboGiven as a single-dose, powder packet to mix with water | Drug | Blinded: Placebo |
| Usual Care High Resolution Anoscopy (HRA)Also: HRANon-investigational HRA will be performed | Procedure or surgery | Blinded: EXE-346 probiotic, Blinded: Placebo |
Primary outcome
Proportion of participants with no disease present
Time frame: Up to 36 weeks
No anal disease defined as complete regression of lesions as determined by examination of biopsies obtained at HRA
Proportion of participants reporting treatment-emergent adverse events
Time frame: Up to 36 weeks
The frequency of participants reporting adverse events by group will be classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0
2 secondary outcomes
Proportion of participants with demonstrated disease regression
Time frame: Up to 36 weeks
Proportion of participants with HPV-negative status
Time frame: 1 day
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2026.
- Individual participant dataSharing planned: Yes. De-identified information will be shared with study collaborators
Related trials for HSIL, High Grade Squamous Intraepithelial Lesion
Active, not recruitingObservational study
Predictive Biomarkers for Precision Management of Pre-cancerous Cervical Neoplasia
HSIL, High Grade Squamous Intraepithelial Lesion, DNA Methylation
Recruiting
Multicenter Prospective Non-randomized Controlled Study of Ella Photodynamic Therapy for Cervical HSIL/CIN2
HSIL, High Grade Squamous Intraepithelial Lesion, CIN 2
Active, not recruiting
Screening Algorithms for Cervical and Anal High-Grade Squamous Intraepithelial Lesions in People With HIV in Mexico and Puerto Rico
AIDS-Related Anal Carcinoma, AIDS-Related Cervical Carcinoma
Active, not recruitingObservational study
Anal High-risk HPV, HSIL, and Microbiome Among Hispanic Peoples Living With HIV (PLWH)
Human Immunodeficiency Virus, Human Papillomavirus-Related Anal Squamous Cell Carcinoma
RecruitingPhase 1
Safety of Anal Curcumin
Anal High Grade Squamous Intraepithelial Lesion
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Joel Palefsky, MD principal investigator
University of California, San Francisco
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing EXE-346 Probiotic in people with HSIL, High Grade Squamous Intraepithelial Lesion and HPV-Related Squamous Cell Carcinoma, run by University of California, San Francisco at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ross Jamison ((415) 353-9042, Ross.Jamison@ucsf.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of participants with no disease present (time frame: Up to 36 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2026.