Study of EXE-346 Live Biotherapeutic to Reduce High Bowel Movement Frequency in Subjects With an IPAA (PROF) (PROF)

November 14, 2023 updated by: Exegi Pharma, LLC

A Phase 1b/2 Study to Demonstrate the Safety and Efficacy of EXE-346 Live Biotherapeutic to Reduce High Bowel Movement Frequency in Subjects With an Ileal Pouch-Anal Anastomosis (PROF). The "PROF" Study.

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 movement frequency in patients with an ileal pouch-anal anastomosis (IPAA) and lead to a higher quality of life.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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 patients with an IPAA and lead to a higher quality of life. EXE-346 is a live biotherapeutic product containing a fixed proportion mixture of 8 individual bacterial strains.

The Phase 1b part of the study is an open label (OL), single-arm study to assess the safety of EXE-346 administered orally for up to 4 weeks.

The Phase 2 part of the study is a randomized, double-blinded study to assess the safety and efficacy of the same dose of EXE-346 administered orally for up to 8 weeks, compared with placebo. Subjects who complete the Phase 2 double-blinded part of the study will be eligible to participate in an optional open label extension phase to receive EXE-346 for up to 8 weeks.

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Not yet recruiting
        • University of Maryland School of Medicine
        • Principal Investigator:
          • Raymond K Cross, MD, MS
        • Contact:
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic Department of Gastroenterology
        • Contact:
        • Principal Investigator:
          • Darrell S Pardi, MD, MSc
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Not yet recruiting
        • Washington University School of Medicine
        • Contact:
        • Principal Investigator:
          • Parakkal Deepak, MBBS, MS
    • New York
      • New York, New York, United States, 10016
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • Recruiting
        • University of North Carolina At Chapel Hill
        • Contact:
        • Principal Investigator:
          • Hans H Herfarth, MD, PhD
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Not yet recruiting
        • Penn State Health (Milton S. Hershey Medical Center)
        • Contact:
        • Principal Investigator:
          • Michael Deutsch, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

INCLUSION CRITERIA

  1. [Phase 1b only] Subject is a male or female and is between the age of 18 to 65 years, inclusive, at screening.
  2. [Phase 1b only] Subject has had a documented pouchoscopy within 12 months prior to screening.
  3. [Phase 2 only] Subject is a male or female and is aged 18 years or older at screening.
  4. 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.
  5. Subject has had an IPAA for at least 6 months prior to screening.
  6. Subject has an average daily bowel movement frequency of at least 10 bowel movements recorded during screening and has correctly completed at least 7 days of electronic diary (eDiary) entries during the screening period.
  7. Female subjects of childbearing potential must have a negative serum pregnancy test result at screening and must not be lactating and/or breastfeeding.
  8. Female subjects of childbearing potential and male subjects with partners of childbearing potential must agree to use proper contraceptive methods to avoid pregnancy during the study.
  9. [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.
  10. [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

  1. [Phase 1b only] Subject has Crohn's-like disease of the pouch, as indicated by their most recent pouchoscopy during the 12 months prior to screening.
  2. [Phase 1b only] Subject has a stricture of the IPAA or afferent limb stricture, as indicated by their most recent pouchoscopy during the 12 months prior to screening.
  3. [Phase 2 only] Subject has Crohn's-like disease of the pouch, as indicated by the pouchoscopy conducted during study screening.
  4. [Phase 2 only] Subject has isolated severe cuffitis without pouch inflammation (endoscopic modified Pouch Disease Activity Index (mPDAI) score of 2 or lower).
  5. [Phase 2 only] Subject has a stricture of the IPAA or afferent limb stricture as indicated by the pouchoscopy conducted during study screening.
  6. Subject has enterocutaneous or recto- or pouch-vaginal fistula.
  7. Subject has active Clostridium difficile infection.
  8. Subject has known or suspected active cytomegalovirus (CMV) infection.
  9. Subject initiated a new treatment with antibiotics or antimotility therapies within the 2 weeks prior to screening or plans to start a new or change doses of a current treatment during the study period.
  10. Subject has taken biologics, azathioprine, or methotrexate within the 12 weeks prior to screening or systemic steroids within 4 weeks of screening.
  11. Subject is taking NSAIDs as a long-term treatment (i.e., consistent use for at least 4 days/week each month).
  12. Subject has a known history or positive test during screening for HIV, HIV-1, HIV-2, or active hepatitis B virus (HBV) or hepatitis C virus (HCV).
  13. Subject has a positive reverse transcriptase-polymerase chain reaction (PCR) diagnostic test for SARS-CoV-2 (COVID-19) within the 14 days prior to screening.
  14. Subject has a history of malignancy within the 5 years prior to screening, with the exception of nonmelanoma skin cancer that has been treated with no evidence of recurrence, treated cervical dysplasia, or treated in situ grade 1 cervical cancer.
  15. Subject has estimated glomerular filtration rate <30 mL/min/1.73 m^2 at screening.
  16. Subject has uncontrolled hypertension at screening.
  17. Subject has known hypersensitivity to EXE-346 or any product components.
  18. Female subject is pregnant or lactating and/or breastfeeding.
  19. Subject has participated in any clinical study of an approved or unapproved investigational medicinal product within the 30 days prior to screening.

  20. Subject has any disorder that, in the investigator's opinion, might jeopardize the subject's safety or compliance with the protocol, including but not limited to:

    1. Decompensated liver disease
    2. Elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), or bilirubin >2 × upper limit of normal (ULN)
    3. Primary sclerosing cholangitis with elevated transaminases
  21. [Phase 2 OL extension only] Subject has developed any medical or psychologic condition excluded in the Phase 2 double-blinded part of the study or which, in the investigator's opinion, might create undue risk to the subject, interfere with the subject's ability to comply with the protocol requirements, or interfere with the subject's ability to complete the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase 1b Open Label
EXE-346 live biotherapeutic product, 1500x10^9 colony forming units (CFU) twice daily (BID), 4 weeks
Biological: EXE-346
EXE-346 contains a proprietary, fixed-dose, lyophilized blend of 8 strains of gram positive, lactic acid bacteria. EXE-346 excipients are maltose and silicon dioxide.
Experimental: Phase 2: Active Arm
EXE-346 live biotherapeutic product, 1500x10^9 CFU BID, 8 weeks
Biological: EXE-346
EXE-346 contains a proprietary, fixed-dose, lyophilized blend of 8 strains of gram positive, lactic acid bacteria. EXE-346 excipients are maltose and silicon dioxide.
Placebo Comparator: Phase 2: Placebo Arm
Powder containing same inactive ingredients as EXE-346 but none of the active ingredients, BID, 8 weeks
Other: Placebo
Placebo contains excipients maltose and silicon dioxide.
Experimental: Phase 2 Open Label Extension (optional)
EXE-346 live biotherapeutic product, 1500x10^9 CFU BID, 8 weeks
Biological: EXE-346
EXE-346 contains a proprietary, fixed-dose, lyophilized blend of 8 strains of gram positive, lactic acid bacteria. EXE-346 excipients are maltose and silicon dioxide.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1b: Incidence, Severity, Relatedness, and Frequency of Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE)
Time Frame: 4 weeks
To assess the safety of EXE-346 using incidence, severity, relationship to study treatment, and frequency of treatment emergent adverse events (TEAE) and serious adverse events (SAE).
4 weeks
Phase 1b: Number of Participants with Abnormal Physical Examinations
Time Frame: 4 weeks
To assess the safety of EXE-346 using abnormal findings in physical examinations after the start of study treatment that suggest a clinically significant worsening of medical issue.
4 weeks
Phase 1b: Number of Participants with Abnormal Vital Signs
Time Frame: 4 weeks
To assess the safety of EXE-346 using abnormal findings in vital sign readings after the start of study treatment that suggest a clinically significant worsening of medical issue, including blood pressure.
4 weeks
Phase 1b: Number of Participants with Abnormal Safety Labs
Time Frame: 4 weeks
To assess the safety of EXE-346 using markedly abnormal findings in safety labs after the start of study treatment that suggest a clinically significant worsening of medical issue.
4 weeks
Phase 1b: Study Treatment Discontinuation Due to Treatment Emergent Adverse Events (TEAEs)
Time Frame: 4 weeks
To assess the safety of EXE-346 using study treatment discontinuation due to TEAE(s).
4 weeks
Phase 2: Incidence, Severity, Relatedness, and Frequency of Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE)
Time Frame: 8 weeks
To assess the safety of EXE-346 using incidence, severity, relationship to study treatment, and frequency of TEAEs and SAEs.
8 weeks
Phase 2: Number of Participants with Abnormal Physical Examinations
Time Frame: 8 weeks
To assess the safety of EXE-346 using abnormal findings in physical examinations after the start of study treatment that suggest a clinically significant worsening of medical issue.
8 weeks
Phase 2: Number of Participants with Abnormal Vital Signs
Time Frame: 8 weeks
To assess the safety of EXE-346 using abnormal findings in vital sign readings after the start of study treatment that suggest a clinically significant worsening of medical issue, including blood pressure.
8 weeks
Phase 2: Number of Participants with Abnormal Safety Labs
Time Frame: 8 weeks
To assess the safety of EXE-346 using markedly abnormal findings in safety labs after the start of study treatment that suggest a clinically significant worsening of medical issue.
8 weeks
Phase 2: Study Treatment Discontinuation Due to Treatment Emergent Adverse Events (TEAEs)
Time Frame: 8 weeks
To assess the safety of EXE-346 using study treatment discontinuation due to TEAE(s).
8 weeks
Phase 2: Change in Total Daily Bowel Movement Frequency
Time Frame: 8 weeks
To assess the efficacy of EXE-346 to reduce the total daily bowel movement frequency using change in average daily bowel movement frequency from baseline to each post-baseline week
8 weeks
Phase 2 Open Label: Incidence, Severity, Relatedness, and Frequency of Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE)
Time Frame: 8 weeks
To assess the safety of EXE-346 using incidence, severity, relationship to study treatment, and frequency of TEAEs and SAEs.
8 weeks
Phase 2 Open Label: Number of Participants with Abnormal Physical Examinations
Time Frame: 8 weeks
To assess the safety of EXE-346 using abnormal findings in physical examinations after the start of study treatment that suggest a clinically significant worsening of medical issue.
8 weeks
Phase 2 Open Label: Number of Participants with Abnormal Vital Signs
Time Frame: 8 weeks
To assess the safety of EXE-346 using abnormal findings in vital sign readings after the start of study treatment that suggest a clinically significant worsening of medical issue, including blood pressure.
8 weeks
Phase 2 Open Label: Number of Participants with Abnormal Safety Labs
Time Frame: 8 weeks
To assess the safety of EXE-346 using markedly abnormal findings in safety labs after the start of study treatment that suggest a clinically significant worsening of medical issue.
8 weeks
Phase 2 Open Label: Study Treatment Discontinuation Due to Treatment Emergent Adverse Events (TEAEs)
Time Frame: 8 weeks
To assess the safety of EXE-346 using study treatment discontinuation due to TEAE(s).
8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1b: Bowel Movement Frequency
Time Frame: 4 weeks
To assess the effect of EXE-346 on bowel movement frequency using change in average daily bowel movement frequency from baseline to each post-baseline week
4 weeks
Phase 1b: Nighttime Awakening Frequency
Time Frame: 4 weeks
To assess the effect of EXE-346 on nighttime awakening frequency using change in average nighttime awakenings for bowel movements from baseline to each post-baseline week
4 weeks
Phase 1b: Bowel Movement Consistency
Time Frame: 4 weeks
To assess the effect of EXE-346 on bowel movement consistency using change in average consistency of daily bowel movements from baseline to each post-baseline week
4 weeks
Phase 2: Nighttime Awakening Frequency
Time Frame: 8 weeks
To assess the effect of EXE 346 on nighttime awakening frequency using change in average nighttime awakenings for bowel movements from baseline to each post-baseline week
8 weeks
Phase 2: Bowel Movement Consistency
Time Frame: 8 weeks
To assess the effect of EXE-346 on bowel movement consistency using change in average consistency of daily bowel movements from baseline to each post-baseline week
8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Exegi Pharma, LLC

Collaborators

The Emmes Company, LLC

Investigators

  • Study Director: Melody Khorrami, PharmD, RPh, Exegi Pharma, LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 11, 2023

Primary Completion (Estimated)

January 1, 2025

Study Completion (Estimated)

June 1, 2025

Study Registration Dates

First Submitted

May 30, 2023

First Submitted That Met QC Criteria

July 3, 2023

First Posted (Actual)

July 10, 2023

Study Record Updates

Last Update Posted (Actual)

November 15, 2023

Last Update Submitted That Met QC Criteria

November 14, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • 28193

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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