<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03832400</url>
  </required_header>
  <id_info>
    <org_study_id>MET-2-201</org_study_id>
    <nct_id>NCT03832400</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of Microbial Ecosystem Therapeutic-2 (MET-2) in Patients With Ulcerative Colitis (UC)</brief_title>
  <official_title>A Phase 1b, Placebo-controlled, Study of the Safety and Efficacy of MET-2 in Patients With Ulcerative Colitis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NuBiyota</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>NuBiyota</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To define the parameters for dose-dependent engraftment of MET-2 commensal bacteria for the&#xD;
      treatment of mild to moderate ulcerative colitis&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will deliver MET-2 at two different doses via an oral capsule in patients with&#xD;
      active mucosal inflammation and observe its safety, tolerability, pharmacokinetics (PK),&#xD;
      pharmacodynamics (PD) and clinical efficacy as compared to placebo. The goal is to define the&#xD;
      parameters for dose-dependent engraftment of MET-2 commensal bacteria for the treatment of&#xD;
      mild to moderate ulcerative colitis not fully responsive to conventional therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 4, 2019</start_date>
  <completion_date type="Actual">March 1, 2020</completion_date>
  <primary_completion_date type="Actual">March 1, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>This is a Phase 1b, placebo-controlled, multiple dose pilot study.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>The assessor will be blinded as to which dosing arm the subjects are assigned.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Gut Microbiome restoration</measure>
    <time_frame>Baseline vs. day 42</time_frame>
    <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</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assessment of mucosal healing</measure>
    <time_frame>Baseline vs. Day 42</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inflammatory Bowel Disease Questionnaire</measure>
    <time_frame>Baseline vs. Day 42</time_frame>
    <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.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">11</enrollment>
  <condition>Ulcerative Colitis</condition>
  <arm_group>
    <arm_group_label>MET-2 20 g</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <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</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MET-2 40 g</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <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</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo oral capsule</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects receive 10 placebo capsules that are identical in appearance to the MET-2 capsules</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>MET-2</intervention_name>
    <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.</description>
    <arm_group_label>MET-2 20 g</arm_group_label>
    <arm_group_label>MET-2 40 g</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo oral capsule</intervention_name>
    <description>Placebo oral capsule which is identical to the MET-2 capsules.</description>
    <arm_group_label>Placebo oral capsule</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Mild to Moderate UC.&#xD;
&#xD;
          2. ≥ 18 years old.&#xD;
&#xD;
          3. Able to provide informed consent, or have a caregiver able to provide consent.&#xD;
&#xD;
          4. Subjects must have a documented diagnosis (radiologic or endoscopic with histology) of&#xD;
             UC for &gt;3 months before screening. The following must be available in each subject's&#xD;
             source documentation:&#xD;
&#xD;
               -  A biopsy report to confirm the histological diagnosis&#xD;
&#xD;
               -  A report documenting disease duration and medication history prior to study&#xD;
                  colonoscopy&#xD;
&#xD;
          5. Subjects receiving any treatment(s) forUC are eligible provided they are anticipated&#xD;
             to be on a stable dose for the duration of the study period and have been on therapy&#xD;
             prior to the randomization visit for the following amount of time:&#xD;
&#xD;
             Prednisone - 4 weeks; Budesonide - 4 weeks; 5-aminosalicylic acid (5-ASA) containing&#xD;
             products - 4 weeks; Thiopurine analogs (azathioprine, 6-mercaptopurine) - 12 weeks;&#xD;
             Biologic therapy (infliximab, adalimumab, vedolizumab) - 12 weeks; Tofacitinib - 8&#xD;
             weeks.&#xD;
&#xD;
             No change in dose is permitted for the following time period prior to the&#xD;
             randomization visit:&#xD;
&#xD;
             Prednisone - 2 weeks; Budesonide - 4 weeks; 5-ASA containing products - 4 weeks;&#xD;
             Thiopurine analogs (azathioprine, 6-mercaptopurine) - 6 weeks; Biologic therapy&#xD;
             (infliximab, adalimumab, vedolizumab) - 6 weeks; Tofacitinib - 4 weeks.&#xD;
&#xD;
          6. Subjects are males or nonpregnant, nonlactating females who, if sexually active, agree&#xD;
             to comply with the contraceptive requirements of the protocol, or females of&#xD;
             nonchildbearing potential. Males and females of reproductive potential who are&#xD;
             sexually active must agree to use acceptable contraception for the duration of the&#xD;
             study.&#xD;
&#xD;
          7. Willing to participate in follow up as part of the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Ulcerative colitis with disease limited to only the distal rectum (&lt;5cm from dentate&#xD;
             line).&#xD;
&#xD;
          2. Subjects with indeterminate colitis, microscopic colitis, ischemic colitis, infectious&#xD;
             colitis, or clinical/histologic findings suggestive of Crohn's disease will be&#xD;
             excluded.&#xD;
&#xD;
          3. Subjects with colonic dysplasia or neoplasia. (Subjects with prior history of&#xD;
             adenomatous polyps will be eligible if the polyps have been completely removed).&#xD;
&#xD;
          4. Subjects with toxic megacolon or hospitalized for ulcerative colitis.&#xD;
&#xD;
          5. Subjects with colonic stricture, past medical history of colonic resection, a history&#xD;
             of bowel surgery within 6 months before screening, or who are likely to require&#xD;
             surgery for UC during the treatment period.&#xD;
&#xD;
          6. Use of antibiotics within 6 weeks of randomization visit.&#xD;
&#xD;
          7. Allergy to vancomycin.&#xD;
&#xD;
          8. Elective surgery that will require preoperative antibiotics planned within 3 months of&#xD;
             enrolment.&#xD;
&#xD;
          9. Pregnant or planning to get pregnant in the next 6 months.&#xD;
&#xD;
         10. Any condition for which, in the opinion of the investigator, the subject should be&#xD;
             excluded from the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Allan H Steinhart, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>MOUNT SINAI HOSPITAL</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mount Sinai Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G1X5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>November 21, 2018</study_first_submitted>
  <study_first_submitted_qc>February 5, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 6, 2019</study_first_posted>
  <last_update_submitted>April 29, 2021</last_update_submitted>
  <last_update_submitted_qc>April 29, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colitis</mesh_term>
    <mesh_term>Colitis, Ulcerative</mesh_term>
    <mesh_term>Ulcer</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03832400
org study id: MET-2-201
nct id: NCT03832400
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
To define the parameters for dose-dependent engraftment of MET-2 commensal bacteria for the
      treatment of mild to moderate ulcerative colitis
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.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a Phase 1b, placebo-controlled, multiple dose pilot study.
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: The assessor will be blinded as to which dosing arm the subjects are assigned.
measure: Gut Microbiome restoration
time frame: Baseline vs. day 42
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
measure: Assessment of mucosal healing
time frame: Baseline vs. Day 42
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.
measure: Inflammatory Bowel Disease Questionnaire
time frame: Baseline vs. Day 42
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.
arm group label: MET-2 20 g
arm group type: Experimental
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 group label: MET-2 40 g
arm group type: Experimental
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 group label: Placebo oral capsule
arm group type: Placebo Comparator
description: Subjects receive 10 placebo capsules that are identical in appearance to the MET-2 capsules
intervention type: Biological
intervention name: MET-2
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.
arm group label: MET-2 20 g
arm group label: MET-2 40 g
intervention type: Drug
intervention name: Placebo oral capsule
description: Placebo oral capsule which is identical to the MET-2 capsules.
arm group label: Placebo oral capsule
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Allan H Steinhart, MD
role: Principal Investigator
affiliation: MOUNT SINAI HOSPITAL
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Colitis
mesh term: Colitis, Ulcerative
mesh term: Ulcer
sharing ipd: Undecided