Ileal Pouch
Conditions
Keywords
Pouchitis, Pouch, Ileal Pouch Anastomosis, IPAA
Brief summary
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.
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.
Interventions
BIOLOGICALEXE-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.
OTHERPlacebo
Placebo contains excipients maltose and silicon dioxide.
Sponsors
Exegi Pharma, LLC
The Emmes Company, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
- Phase 1b Only 1. Subject is a male or female and is between the age of 18 to 70 years, inclusive, at screening. 2. Subject has had a documented pouchoscopy within 12 months prior to screening. 3. Subject or the subject's legally authorized representative is willing and able to provide written informed consent prior to the initiation of any study-related procedures. 4. 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 eDiary entries during the screening period (Days -13 to 0). Inclusion Criteria - Phase 2 Double-Blinded Part Only 1. Subject is a male or female and is aged 18 years or older at screening. 2. Subject is willing and able to provide written informed consent prior to the initiation of any study-related procedures. 3. 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 eDiary entries during the screening period (Days -21 to 0). Inclusion Criteria - Both Phase 1b and Phase 2 Double-Blinded Parts 1. Subject has had an IPAA for at least 6 months prior to screening. 2. Female subjects of childbearing potential must have a negative serum pregnancy test result at screening and must not be lactating and/or breastfeeding. 3. Subjects (female subjects of childbearing potential and male subjects with partners of childbearing potential) must agree to use proper contraceptive methods (see Section 13.2 for contraceptive guidance) to avoid pregnancy during the study. Nonchildbearing potential is defined as at least 6 weeks after a hysterectomy with or without surgical bilateral oophorectomy or postmenopausal (at least 12 months since natural amenorrhea). Inclusion Criteria - Optional Open-Label Extension Phase Only 1. Subjects must have completed the Phase 2 double-blinded part of the study and are willing to participate in the optional open-label extension phase. Note: Subjects who discontinued study treatment in the Phase 2 double-blinded part but who have remained in the study for safety monitoring are eligible for continued safety monitoring in the optional open-label extension phase; however, study treatment will not be re-started in such subjects. 2. Subjects must understand the study procedures, the risks involved, and are willing to continue to adhere to the study visit/protocol schedule.
Exclusion criteria
Subjects meeting any of the criteria specified below for the study phase in which they are enrolling will be excluded from the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b: Incidence, Severity, Relatedness, and Frequency of Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | 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). |
| Phase 1b: Number of Participants with Abnormal Physical Examinations | 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. |
| Phase 1b: Number of Participants with Abnormal Vital Signs | 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. |
| Phase 1b: Number of Participants with Abnormal Safety Labs | 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. |
| Phase 1b: Study Treatment Discontinuation Due to Treatment Emergent Adverse Events (TEAEs) | 4 weeks | To assess the safety of EXE-346 using study treatment discontinuation due to TEAE(s). |
| Phase 2: Incidence, Severity, Relatedness, and Frequency of Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | 8 weeks | To assess the safety of EXE-346 using incidence, severity, relationship to study treatment, and frequency of TEAEs and SAEs. |
| Phase 2: Number of Participants with Abnormal Physical Examinations | 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. |
| Phase 2: Number of Participants with Abnormal Vital Signs | 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. |
| Phase 2: Number of Participants with Abnormal Safety Labs | 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. |
| Phase 2: Study Treatment Discontinuation Due to Treatment Emergent Adverse Events (TEAEs) | 8 weeks | To assess the safety of EXE-346 using study treatment discontinuation due to TEAE(s). |
| Phase 2: Change in Total Daily Bowel Movement Frequency | 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 |
| Phase 2 Open Label: Incidence, Severity, Relatedness, and Frequency of Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | 8 weeks | To assess the safety of EXE-346 using incidence, severity, relationship to study treatment, and frequency of TEAEs and SAEs. |
| Phase 2 Open Label: Number of Participants with Abnormal Physical Examinations | 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. |
| Phase 2 Open Label: Number of Participants with Abnormal Vital Signs | 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. |
| Phase 2 Open Label: Number of Participants with Abnormal Safety Labs | 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. |
| Phase 2 Open Label: Study Treatment Discontinuation Due to Treatment Emergent Adverse Events (TEAEs) | 8 weeks | To assess the safety of EXE-346 using study treatment discontinuation due to TEAE(s). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b: Bowel Movement Frequency | 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 |
| Phase 1b: Nighttime Awakening Frequency | 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 |
| Phase 1b: Bowel Movement Consistency | 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 |
| Phase 2: Nighttime Awakening Frequency | 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 |
| Phase 2: Bowel Movement Consistency | 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 |
Countries
United States
Contacts
CONTACTEmmes Project Management
STUDY_DIRECTORJulia Collins, MS
Exegi Pharma, LLC
Outcome results
None listed