EXE-346 for Ileal Pouch

(PROF Trial)

Recruiting at 10 trial locations

Overseen By Emmes Project Management

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Exegi Pharma, LLC

Must not be taking: Biologics, Opioids, Probiotics, others

Disqualifiers: Crohn's-like disease, Stricture, Hypertension, others

Compensation: Varies

Number of Visits: Unknown

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called EXE-346, a live biotherapeutic designed to help individuals with an ileal pouch-anal anastomosis (IPAA) by reducing bowel movement frequency and enhancing overall quality of life. The study will assess the treatment's safety and effectiveness across different phases, with some participants receiving the active treatment and others a placebo (inactive substance). Individuals who have had an IPAA for at least six months and typically experience at least ten bowel movements a day might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial requires that you stop taking certain medications before joining. Specifically, you must not have taken biologics, azathioprine, methotrexate, or small molecules like JAK inhibitors within 12 weeks before screening, and systemic steroids within 4 weeks before screening. Additionally, you should not have taken opioids or probiotics within 2 weeks before screening, and you should not start new antibiotics or antimotility therapies or change doses of current treatments during the study.

Is there any evidence suggesting that EXE-346 is likely to be safe for humans?

Research has shown that EXE-346, a treatment using live bacteria, is generally safe and well-tolerated. In earlier studies, participants experienced only mild side effects, which were not serious. Other research confirms that EXE-346 is safe for patients with an ileal pouch, indicating that the treatment does not cause significant harm and remains manageable for patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for ileal pouch conditions, which often focus on anti-inflammatory medications and antibiotics, EXE-346 is a live biotherapeutic product that introduces beneficial bacteria directly into the gut. This innovative approach aims to restore a healthy balance of gut microbiota, potentially offering a more natural way to manage symptoms. Researchers are excited because EXE-346 could provide a targeted solution with fewer side effects compared to traditional drug therapies. Additionally, its twice-daily administration allows for a consistent therapeutic effect, which could lead to more stable symptom control.

What evidence suggests that EXE-346 might be an effective treatment for an ileal pouch?

Research shows that EXE-346, a treatment made from live probiotics, may benefit people with an ileal pouch (a surgically created internal pouch for stool). Previous studies found that patients experienced fewer bowel movements, suggesting an improvement in quality of life. The probiotics in EXE-346 are beneficial bacteria that support gut health. Safety results have been positive, with no major side effects reported. This trial will evaluate EXE-346 in different phases, including a placebo arm, to further assess its effectiveness and safety. This treatment might be a useful option for managing symptoms related to an ileal pouch. ^{1 6 7 8 9}

Who Is on the Research Team?

Julia Collins, MS

Principal Investigator

Exegi Pharma, LLC

Are You a Good Fit for This Trial?

Adults with an ileal pouch-anal anastomosis (IPAA) experiencing at least 10 bowel movements daily, who've kept a diary of this during screening. They must not be pregnant or breastfeeding and agree to use contraception. Exclusions include long-term NSAID users, those with certain pouch complications or infections, recent biologic or steroid treatments, significant past illnesses like cancer within 5 years (except some skin cancers), and severe kidney issues.

Inclusion Criteria

Subject or the subject's legally acceptable representative is willing and able to provide written informed consent prior to the initiation of any study-related procedures.

[Phase 2 OL extension only] Subject must have completed the Phase 2 double-blinded part of the study and be willing to participate in the optional open-label extension phase.

[Phase 2 OL extension only] Subject must understand the study procedures, the risks involved, and be willing to continue to adhere to the study visit/protocol schedule.

Exclusion Criteria

Subject has participated in any clinical study of an approved or unapproved investigational medicinal product within the 30 days prior to screening.

I regularly take NSAIDs at least 4 days a week every month.

My pouchoscopy shows I have Crohn's-like disease of the pouch.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1b Treatment

Open label, single-arm study to assess the safety of EXE-346 administered orally

4 weeks

Regular visits for safety assessments

Phase 2 Treatment

Randomized, double-blinded study to assess the safety and efficacy of EXE-346 compared with placebo

8 weeks

Regular visits for efficacy and safety assessments

Open-label Extension (optional)

Participants may opt into continuation of treatment with EXE-346 for additional safety and efficacy assessment

8 weeks

Regular visits for safety and efficacy assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• EXE-346

Trial Overview The trial is testing EXE-346, a live biotherapeutic product against a placebo to see if it can reduce the frequency of bowel movements in patients with IPAA. The goal is to improve their quality of life by potentially normalizing bowel function.

How Is the Trial Designed?

Group I: Phase 2: Active Arm Experimental Treatment 1 Intervention

EXE-346 live biotherapeutic product, 1500x10\^9 CFU BID, 8 weeks

Group II: Phase 2 Open Label Extension (optional) Experimental Treatment 1 Intervention

EXE-346 live biotherapeutic product, 1500x10\^9 CFU BID, 8 weeks

Group III: Phase 1b Open Label Experimental Treatment 1 Intervention

EXE-346 live biotherapeutic product, 1500x10\^9 colony forming units (CFU) twice daily (BID), 4 weeks

Group IV: Phase 2: Placebo Arm Placebo Group 1 Intervention

Powder containing same inactive ingredients as EXE-346 but none of the active ingredients, BID, 8 weeks

Who Is Running the Clinical Trial?

Exegi Pharma, LLC

Lead Sponsor

Trials

3

Recruited

220+

The Emmes Company, LLC

Industry Sponsor

Trials

149

Recruited

1,052,000+

Peter Ronco

The Emmes Company, LLC

Chief Executive Officer since 2023

BSc from Nottingham University

Dr. Joe Sliman

The Emmes Company, LLC

Chief Medical Officer since 2020

MD from Uniformed Services University of the Health Sciences, MPH from Johns Hopkins University, BSc in Molecular and Cell Biology from Pennsylvania State University

Published Research Related to This Trial

The International Serious Adverse Event Consortium (SAEC) aims to identify DNA variants that can predict the risk of rare drug-induced serious adverse events (SAEs), such as liver disease and severe skin reactions, by collaborating with pharmaceutical companies and regulatory bodies.

Launched in 2007, the SAEC focuses on making research findings publicly available at no cost, with the goal of enhancing drug safety and understanding the genetic basis of adverse drug reactions through large-scale genomic studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The innovative use of a large-scale industry biomedical consortium to research the genetic basis of drug induced serious adverse events. Holden, AL.[2014]

In a study of 32 patients who developed Crohn's disease-like complications after ileal pouch-anal anastomosis (IPAA), those with fistulas had a high failure rate of 46% when treated with infliximab and azathioprine/6-mercaptopurine, indicating a need for careful management of this condition.

Conversely, patients with stricturing disease or severe pouchitis responded well to treatment with azathioprine/6-mercaptopurine or infliximab, with no need for stomas, suggesting that these conditions can be effectively managed with less aggressive treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infliximab and/or azathioprine in the treatment of Crohn's disease-like complications after IPAA. Haveran, LA., Sehgal, R., Poritz, LS., et al.[2017]

In a study of 507 patients who underwent ileal pouch excision, 15.7% were obese, and while the overall outcomes were similar between obese and nonobese patients, obesity was linked to a significantly higher rate of deep incisional surgical site infections (7.5% vs 2.8%).

Obese patients also had a higher rate of readmission (28.3% vs 16%) compared to nonobese patients, indicating that while the surgery can be performed safely, obesity may complicate recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ileal Pouch Excision can Be Performed With Similar Outcomes in Obese Patients Compared to Nonobese Counterparts: An Assessment From American College of Surgeons National Surgical Quality Improvement Program. Esen, E., Aytac, E., Aydinli, HH., et al.[2022]

Following the 2011 FDA warning about adverse events related to transvaginal mesh for pelvic organ prolapse, the use of mesh slings for stress urinary incontinence (SUI) in New York decreased by 43% from 2011 to 2015, indicating a significant impact of regulatory notifications on clinical practice.

The decline in mesh sling usage was primarily observed among non-FPMRS (Female Pelvic Medicine and Reconstructive Surgery) providers, while FPMRS-certified physicians continued to perform a higher proportion of sling procedures, suggesting that specialized training may influence the adoption and safety perceptions of these interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trends of Mesh Utilization for Stress Urinary Incontinence Before and After the 2011 Food and Drug Administration Notification Between FPMRS-Certified and Non-FPMRS-Certified Physicians: A Statewide All-Payer Database Analysis. Siegal, AR., Huang, Z., Gross, MD., et al.[2022]

In a study of 735 patients across 24 hospitals in Spain, 10.5% experienced adverse events (AEs) related to medical care, with higher rates observed in patients with intrinsic (14.8%) and extrinsic risk factors (16.2%).

A significant portion of AEs (36.5%) were preventable, primarily linked to nosocomial infections and surgical procedures, leading to an additional 527 days of hospital stay, highlighting the need for improved patient safety measures in surgical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adverse events in general and digestive surgery departments in Spanish hospitals]. Aranaz-Andrés, JM., Ruiz-López, P., Aibar-Remón, C., et al.[2019]

Ileal pouch-anal anastomosis (IPAA) surgery is the standard treatment for ulcerative colitis, preserving fecal continence and gastrointestinal function, but it can lead to various complications that require careful imaging for diagnosis.

The article proposes structured reporting templates for MRI and water-soluble contrast enema (WSCE) to improve the evaluation of complications in patients post-IPAA surgery, based on the authors' extensive clinical experience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reporting Templates for MRI and Water-Soluble Contrast Enema in Patients With Ileal Pouch-Anal Anastomosis: Experience From a Large Referral Center. Huang, C., Remzi, FH., Dane, B., et al.[2021]

The International Serious Adverse Events Consortium is focused on understanding the genetic and biological factors that contribute to serious adverse events caused by drugs, which can enhance the safety of medications.

By generating new insights into these adverse events, the consortium aims to improve the development and decision-making processes in the pharmaceutical industry, potentially leading to safer drug options for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The international serious adverse events consortium. Holden, AL., Contreras, JL., John, S., et al.[2018]

In a study of 445 ulcerative colitis patients undergoing proctocolectomy with ileal pouch-anal anastomosis, preoperative anti-tumor necrosis factor therapy did not lead to increased postoperative complications.

High-dose corticosteroids were linked to a higher risk of anastomotic leaks and wound dehiscence, but did not significantly increase pouch failure rates, suggesting that while corticosteroids pose some risk, the overall outcomes remain favorable in experienced surgical centers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Restorative Proctocolectomy in Ulcerative Colitis: Effect of Preoperative Immunomodulatory Therapy on Postoperative Complications and Pouch Failure. Karjalainen, EK., Renkonen-Sinisalo, L., Mustonen, HK., et al.[2022]

In a survey of 17 European countries, it was found that while 13 have regulations for reporting adverse vaccine reactions, only six have full-time professionals dedicated to vaccine safety, highlighting a significant gap in resources and expertise.

The study revealed that reporting systems for adverse events following immunization (AEFI) are inconsistent across countries, with many lacking standardized definitions and reporting forms specifically designed for vaccines, which complicates the assessment of vaccine safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccinovigilance in Europe--need for timeliness, standardization and resources. Lankinen, KS., Pastila, S., Kilpi, T., et al.[2015]

In a study of 28 patients with refractory pouch complications after ileal pouch-anal anastomosis (IPAA), infliximab (IFX) demonstrated a high initial clinical response rate of 88% for luminal inflammation and 86% for pouch fistulas at 10 weeks.

After a median follow-up of 20 months, 56% of patients maintained their clinical response, indicating that IFX can be an effective long-term treatment option for patients with chronic pouchitis and related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of infliximab in refractory pouchitis and Crohn's disease-related complications of the pouch: a Belgian case series. Ferrante, M., D'Haens, G., Dewit, O., et al.[2022]

Citations

1. biospace.com biospace.com/press-releases/exegi-pharma-positive-topline-results-in-exe-346-prof-phase-1b-study

ExeGi Pharma Positive Topline Results in EXE-346 PROF ... PROF study demonstrates safety of EXE-346 drug product in pouch anastomosis patients at 3,000 billion live probiotic consumption per day for ...

2. synapse.patsnap.com synapse.patsnap.com/article/exegi-pharma-reports-positive-phase-1b-results-for-exe-346-study

ExeGi Pharma Reports Positive Phase 1b Results for EXE- ... These findings suggest that EXE-346 could potentially improve the quality of life for IPAA patients by significantly reducing both stool ...

3. mayo.edu mayo.edu/research/clinical-trials/cls-20583998

Study of EXE-346 Live Biotherapeutic to Reduce High ... The aim of this study is to assess the safety and preliminary efficacy of treatment with EXE-346, a live biotherapeutic, which may reduce bowel ...

4. journals.lww.com journals.lww.com/10.14309/01.ajg.0001134592.85438.bb

S1783 EXE-346 Live Biotherapeutic Reduces High Bowel... S1783 EXE-346 Live Biotherapeutic Reduces High Bowel Movement Frequency in Subjects With an Ileal Pouch-Anal Anastomosis. Herfarth, Hans MD, PhD; Chang ...

5. prnewswire.com prnewswire.com/news-releases/exegi-pharma-positive-topline-results-in-exe-346-prof-phase-1b-study-302333867.html

ExeGi Pharma Positive Topline Results in EXE-346 PROF ... PROF study demonstrates safety of EXE-346 drug product in pouch anastomosis patients at 3,000 billion live probiotic consumption per day for ...

6. mayo.edu mayo.edu/research/clinical-trials/cls-20554899

Study of EXE-346 Live Biotherapeutic to Reduce High ... The purpose of this study is to assess the safety of EXE-346 after 4 weeks of treatment in subjects with an Ileal-Pouch Anal Anastomosis (IPAA) and high bowel ...

7. withpower.com withpower.com/trial/phase-2-pouch-ileal-8-2023-86ab5

EXE-346 for Ileal Pouch (PROF Trial) What safety data exists for EXE-346 or similar treatments? The research articles provided do not contain specific safety data for EXE-346 or similar treatments.

8. firstwordpharma.com firstwordpharma.com/story/5922216

ExeGi Pharma Positive Topline Results in EXE-346 PROF ... PROF study demonstrates safety of EXE-346 drug product in pouch anastomosis patients at 3,000 billion live probiotic consumption per day for ...

9. ctv.veeva.com ctv.veeva.com/study/study-of-exe-346-live-biotherapeutic-to-reduce-high-bowel-movement-frequency-in-subjects-with-an-ipa

Study of EXE-346 Live Biotherapeutic to Reduce High Bowel ... The aim of this study is to assess the safety and preliminary efficacy of treatment with EXE-346 which may reduce bowel movement frequency in ...