Back to resultsSafety and Efficacy of Microbial Ecosystem Therapeutic-2 (MET-2) in Patients With Ulcerative Colitis (UC)
Primary Purpose
Ulcerative Colitis
Status
Completed
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
MET-2
Placebo oral capsule
Sponsored by
About this trial
This is an interventional treatment trial for Ulcerative Colitis
Eligibility Criteria
Inclusion Criteria:
- Mild to Moderate UC.
- ≥ 18 years old.
- Able to provide informed consent, or have a caregiver able to provide consent.
Subjects must have a documented diagnosis (radiologic or endoscopic with histology) of UC for >3 months before screening. The following must be available in each subject's source documentation:
- A biopsy report to confirm the histological diagnosis
- A report documenting disease duration and medication history prior to study colonoscopy
Subjects receiving any treatment(s) forUC are eligible provided they are anticipated to be on a stable dose for the duration of the study period and have been on therapy prior to the randomization visit for the following amount of time:
Prednisone - 4 weeks; Budesonide - 4 weeks; 5-aminosalicylic acid (5-ASA) containing products - 4 weeks; Thiopurine analogs (azathioprine, 6-mercaptopurine) - 12 weeks; Biologic therapy (infliximab, adalimumab, vedolizumab) - 12 weeks; Tofacitinib - 8 weeks.
No change in dose is permitted for the following time period prior to the randomization visit:
Prednisone - 2 weeks; Budesonide - 4 weeks; 5-ASA containing products - 4 weeks; Thiopurine analogs (azathioprine, 6-mercaptopurine) - 6 weeks; Biologic therapy (infliximab, adalimumab, vedolizumab) - 6 weeks; Tofacitinib - 4 weeks.
- Subjects are males or nonpregnant, nonlactating females who, if sexually active, agree to comply with the contraceptive requirements of the protocol, or females of nonchildbearing potential. Males and females of reproductive potential who are sexually active must agree to use acceptable contraception for the duration of the study.
- Willing to participate in follow up as part of the study.
Exclusion Criteria:
- Ulcerative colitis with disease limited to only the distal rectum (<5cm from dentate line).
- Subjects with indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, or clinical/histologic findings suggestive of Crohn's disease will be excluded.
- Subjects with colonic dysplasia or neoplasia. (Subjects with prior history of adenomatous polyps will be eligible if the polyps have been completely removed).
- Subjects with toxic megacolon or hospitalized for ulcerative colitis.
- Subjects with colonic stricture, past medical history of colonic resection, a history of bowel surgery within 6 months before screening, or who are likely to require surgery for UC during the treatment period.
- Use of antibiotics within 6 weeks of randomization visit.
- Allergy to vancomycin.
- Elective surgery that will require preoperative antibiotics planned within 3 months of enrolment.
- Pregnant or planning to get pregnant in the next 6 months.
- Any condition for which, in the opinion of the investigator, the subject should be excluded from the study.
Sites / Locations
- Mount Sinai Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
MET-2 20 g
MET-2 40 g
Placebo oral capsule
Arm Description
Subjects will be given a once-daily loading dose of 5 grams (g) of MET-2 in the form of 10 MET-2 capsules orally for the first 4 days. For the following 10 days, patients will take 1.5 g MET-2 in the form of three MET-2 capsules taken once-daily
Subjects will be given a once-daily loading dose of 10 g of MET-2 in the form of 20 MET-2 capsules orally for the first 4 days. For the following 10 days, subjects will take 1.5 g MET-2 in the form of three MET-2 capsules taken once daily
Subjects receive 10 placebo capsules that are identical in appearance to the MET-2 capsules
Outcomes
Primary Outcome Measures
Gut Microbiome restoration
Microbiologic assessment of fecal deoxyribonucleic acid (DNA) samples will be obtained before, during and after treatment to quantify the change in microbial alpha diversity using statistical methods such as Shannon Diversity Index and Microbiome Health Index
Secondary Outcome Measures
Assessment of mucosal healing
Mucosal biopsies will be taken and assessed. Assessment will be made using the Mayo Score for Ulcerative Colitis. There are four domains in this scale: Stool frequency, Rectal bleeding, Findings on endoscopy, Physician's global assessment. Each domain has a scoring range of 0 - 3, where 0 represents best possible outcome and 3 represents worst possible outcome. Efficacy of treatment will be defined as a 'Findings on endoscopy' score of less than or equal to one.
Inflammatory Bowel Disease Questionnaire
This is a self-administered questionnaire. There are 32 quality of life questions related to bowel function. Each question is rated on a numerical scale. The number of possible ratings varies between questions but is most frequently from 1 to 7.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03832400
Brief Title
Safety and Efficacy of Microbial Ecosystem Therapeutic-2 (MET-2) in Patients With Ulcerative Colitis (UC)
Official Title
A Phase 1b, Placebo-controlled, Study of the Safety and Efficacy of MET-2 in Patients With Ulcerative Colitis
Study Type
Interventional
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
February 4, 2019 (Actual)
Primary Completion Date
March 1, 2020 (Actual)
Study Completion Date
March 1, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NuBiyota
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
To define the parameters for dose-dependent engraftment of MET-2 commensal bacteria for the treatment of mild to moderate ulcerative colitis
Detailed Description
This study will deliver MET-2 at two different doses via an oral capsule in patients with active mucosal inflammation and observe its safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and clinical efficacy as compared to placebo. The goal is to define the parameters for dose-dependent engraftment of MET-2 commensal bacteria for the treatment of mild to moderate ulcerative colitis not fully responsive to conventional therapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ulcerative Colitis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
This is a Phase 1b, placebo-controlled, multiple dose pilot study.
Masking
Outcomes Assessor
Masking Description
The assessor will be blinded as to which dosing arm the subjects are assigned.
Allocation
Randomized
Enrollment
11 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MET-2 20 g
Arm Type
Experimental
Arm Description
Subjects will be given a once-daily loading dose of 5 grams (g) of MET-2 in the form of 10 MET-2 capsules orally for the first 4 days. For the following 10 days, patients will take 1.5 g MET-2 in the form of three MET-2 capsules taken once-daily
Arm Title
MET-2 40 g
Arm Type
Experimental
Arm Description
Subjects will be given a once-daily loading dose of 10 g of MET-2 in the form of 20 MET-2 capsules orally for the first 4 days. For the following 10 days, subjects will take 1.5 g MET-2 in the form of three MET-2 capsules taken once daily
Arm Title
Placebo oral capsule
Arm Type
Placebo Comparator
Arm Description
Subjects receive 10 placebo capsules that are identical in appearance to the MET-2 capsules
Intervention Type
Biological
Intervention Name(s)
MET-2
Intervention Description
MET-2 is a defined consortium of human commensal bacteria derived from a healthy donor, which has the full metabolic functional capacity of fecal microbiota.
Intervention Type
Drug
Intervention Name(s)
Placebo oral capsule
Intervention Description
Placebo oral capsule which is identical to the MET-2 capsules.
Primary Outcome Measure Information:
Title
Gut Microbiome restoration
Description
Microbiologic assessment of fecal deoxyribonucleic acid (DNA) samples will be obtained before, during and after treatment to quantify the change in microbial alpha diversity using statistical methods such as Shannon Diversity Index and Microbiome Health Index
Time Frame
Baseline vs. day 42
Secondary Outcome Measure Information:
Title
Assessment of mucosal healing
Description
Mucosal biopsies will be taken and assessed. Assessment will be made using the Mayo Score for Ulcerative Colitis. There are four domains in this scale: Stool frequency, Rectal bleeding, Findings on endoscopy, Physician's global assessment. Each domain has a scoring range of 0 - 3, where 0 represents best possible outcome and 3 represents worst possible outcome. Efficacy of treatment will be defined as a 'Findings on endoscopy' score of less than or equal to one.
Time Frame
Baseline vs. Day 42
Title
Inflammatory Bowel Disease Questionnaire
Description
This is a self-administered questionnaire. There are 32 quality of life questions related to bowel function. Each question is rated on a numerical scale. The number of possible ratings varies between questions but is most frequently from 1 to 7.
Time Frame
Baseline vs. Day 42
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Mild to Moderate UC.
≥ 18 years old.
Able to provide informed consent, or have a caregiver able to provide consent.
Subjects must have a documented diagnosis (radiologic or endoscopic with histology) of UC for >3 months before screening. The following must be available in each subject's source documentation:
A biopsy report to confirm the histological diagnosis
A report documenting disease duration and medication history prior to study colonoscopy
Subjects receiving any treatment(s) forUC are eligible provided they are anticipated to be on a stable dose for the duration of the study period and have been on therapy prior to the randomization visit for the following amount of time:
Prednisone - 4 weeks; Budesonide - 4 weeks; 5-aminosalicylic acid (5-ASA) containing products - 4 weeks; Thiopurine analogs (azathioprine, 6-mercaptopurine) - 12 weeks; Biologic therapy (infliximab, adalimumab, vedolizumab) - 12 weeks; Tofacitinib - 8 weeks.
No change in dose is permitted for the following time period prior to the randomization visit:
Prednisone - 2 weeks; Budesonide - 4 weeks; 5-ASA containing products - 4 weeks; Thiopurine analogs (azathioprine, 6-mercaptopurine) - 6 weeks; Biologic therapy (infliximab, adalimumab, vedolizumab) - 6 weeks; Tofacitinib - 4 weeks.
Subjects are males or nonpregnant, nonlactating females who, if sexually active, agree to comply with the contraceptive requirements of the protocol, or females of nonchildbearing potential. Males and females of reproductive potential who are sexually active must agree to use acceptable contraception for the duration of the study.
Willing to participate in follow up as part of the study.
Exclusion Criteria:
Ulcerative colitis with disease limited to only the distal rectum (<5cm from dentate line).
Subjects with indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, or clinical/histologic findings suggestive of Crohn's disease will be excluded.
Subjects with colonic dysplasia or neoplasia. (Subjects with prior history of adenomatous polyps will be eligible if the polyps have been completely removed).
Subjects with toxic megacolon or hospitalized for ulcerative colitis.
Subjects with colonic stricture, past medical history of colonic resection, a history of bowel surgery within 6 months before screening, or who are likely to require surgery for UC during the treatment period.
Use of antibiotics within 6 weeks of randomization visit.
Allergy to vancomycin.
Elective surgery that will require preoperative antibiotics planned within 3 months of enrolment.
Pregnant or planning to get pregnant in the next 6 months.
Any condition for which, in the opinion of the investigator, the subject should be excluded from the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Allan H Steinhart, MD
Organizational Affiliation
MOUNT SINAI HOSPITAL
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mount Sinai Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G1X5
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Safety and Efficacy of Microbial Ecosystem Therapeutic-2 (MET-2) in Patients With Ulcerative Colitis (UC)
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