<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/NCT03829475</url>
  </required_header>
  <id_info>
    <org_study_id>2018</org_study_id>
    <nct_id>NCT03829475</nct_id>
  </id_info>
  <brief_title>ICON-2: FMT and Bezlotoxumab Compared to FMT and Placebo for Patients With IBD and CDI</brief_title>
  <acronym>ICON-2</acronym>
  <official_title>A Randomized Controlled Trial to Compare the Effectiveness of Fecal Microbiota Transplantation (FMT) in Combination With Bezlotoxumab Compared to FMT and Placebo for the Prevention of CDI Recurrence in Patients With Inflammatory Bowel Disease and Recurrent Clostridium Difficile Infection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Brigham and Women's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Brigham and Women's Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomized controlled trial to assess the clinical and microbiological impacts of&#xD;
      FMT in combination with Bezlotoxumab (bezlo) compared to FMT in combination with placebo in&#xD;
      patients with both inflammatory bowel disease (IBD) a and clostridium difficile infection&#xD;
      (CDI). The investigators will prospectively enroll up to 150 IBD-CDI patients from 4 tertiary&#xD;
      care FMT referral centers. Patients will be randomized 1:1 to either receive FMT in&#xD;
      combination with Bezlo of FMT and a placebo infusion. Donor stool from healthy donors will be&#xD;
      obtained from OpenBiome. OpenBiome is a nonprofit 501(c)(3) organization that provides&#xD;
      hospitals with screened, filtered, and frozen material ready for clinical use. Patients will&#xD;
      be enrolled and followed prospectively for 3 months post therapy. Stool and blood samples as&#xD;
      well as clinical data will be collected at baseline, week 1, 8 and 12.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 1, 2020</start_date>
  <completion_date type="Anticipated">December 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">July 1, 2023</primary_completion_date>
  <phase>Phase 2</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Clostridium difficile recurrence</measure>
    <time_frame>8 weeks</time_frame>
    <description>positive test for CDI by EIA toxin</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Clostridium difficile recurrence</measure>
    <time_frame>8 weeks</time_frame>
    <description>Diarrhea defined at 3 or more bowel movements bristol 6-7 for 2 consecutive days</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Diarrheal symptoms</measure>
    <time_frame>12 weeks</time_frame>
    <description>Number of Bowel movements daily</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rectal bleeding</measure>
    <time_frame>12 weeks</time_frame>
    <description>presence or absence of rectal bleeding</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Abdominal Pain</measure>
    <time_frame>12 weeks</time_frame>
    <description>presence of absence of abominal pain</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Inflammatory Bowel Diseases</condition>
  <condition>Clostridium Difficile Infection</condition>
  <arm_group>
    <arm_group_label>FMT + Bezlo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients in this arm will received an FMT via colonoscopy ( 250ml) as well as a single IV infusion of bezlotoxumab (10mg/kg) that will take place over 60 mins.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>FMT + Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients in this arm will receive a single FMT via colonoscopy (250ml) and a placebo (saline) infusion (250cc) over</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bezlotoxumab</intervention_name>
    <description>This is a a fully human monoclonal antibody that binds to C. difficile toxin B, and is indicated to prevent recurrence of CDI in adults at risk for recurrent CDI (rCDI).</description>
    <arm_group_label>FMT + Bezlo</arm_group_label>
    <other_name>Zinplava</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>placebo is an infusion of normal saline.</description>
    <arm_group_label>FMT + Placebo</arm_group_label>
    <other_name>Saline</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fecal Microbiota Transplantation</intervention_name>
    <description>FMT is an infusion of prescreened donor stool that will be administered via colonoscopy</description>
    <arm_group_label>FMT + Bezlo</arm_group_label>
    <arm_group_label>FMT + Placebo</arm_group_label>
    <other_name>FMT</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults age 18 or greater&#xD;
&#xD;
          -  History of ≥ 2 episodes of recurrent CDI. CDI is defined as the presence of diarrhea (&#xD;
             Bristol 6 or 7 for 48 hours and a confirmatory test for CDI). Preferred testing will&#xD;
             be a two-step method using GDH/EIA toxin, though PCR will be accepted based on&#xD;
             hospital availability with confirmation of the most recent episode occurring within&#xD;
             the prior 3 months&#xD;
&#xD;
          -  Confirmed diagnosis of IBD (ulcerative colitis, Crohn's disease or indeterminate&#xD;
             colitis)&#xD;
&#xD;
          -  Undergoing FMT via colonoscopy for CDI as part of standard medical care&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unable or unwilling to undergo a colonoscopy&#xD;
&#xD;
          -  Inpatient status, though patients can be screened while inpatients, the must be&#xD;
             outpatient for the planned colonoscopy.&#xD;
&#xD;
          -  Anticipated immediate or upcoming surgery within 30 days&#xD;
&#xD;
          -  Need for continued non-anti-CDI antibiotic therapy&#xD;
&#xD;
          -  History of total proctocolectomy&#xD;
&#xD;
          -  Female patients who are pregnant or breastfeeding or plan to become pregnant in the&#xD;
             next 6 months.&#xD;
&#xD;
          -  Patients who are unable to give informed consent&#xD;
&#xD;
          -  Participation in a clinical trial in the preceding 30 days or simultaneously during&#xD;
             this trial&#xD;
&#xD;
          -  Severe food allergy (anaphylaxis or anaphylactoid-like reaction)&#xD;
&#xD;
          -  Life expectancy &lt; 6 months&#xD;
&#xD;
          -  Unable to adhere to protocol requirements&#xD;
&#xD;
          -  Patient who have received an FMT in the past year&#xD;
&#xD;
          -  Any condition that the physician investigators deems unsafe, including other&#xD;
             conditions or medications that the investigator determines that it will put the&#xD;
             subject at greater risk from FMT&#xD;
&#xD;
          -  Patient who is diagnosed with NYHA class 3 or 4 Heart Failure&#xD;
&#xD;
          -  Lab value of WBC &lt;3.0 x 103/mm3 , Platelets &lt;100 x 103/mm3 , ALT or AST &gt; 1.5 x&#xD;
             institutional ULN&#xD;
&#xD;
          -  EBV or CMV negative if a patient is severely immunosuppressed ( defined as 3 or more&#xD;
             immunosuppressing agents)&#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_contact>
    <last_name>Jennifer Mitri</last_name>
    <phone>6177329223</phone>
    <email>Jjmitri@bwh.harvard.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Jessica Allegretti</last_name>
    <phone>6177326389</phone>
    <email>jallegretti@bwh.harvard.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jessica Allegretti, MD, MPH</last_name>
      <phone>617-732-6389</phone>
      <email>jallegretti@partners.org</email>
    </contact>
    <contact_backup>
      <last_name>Jen Mitri</last_name>
      <phone>617-732-9223</phone>
      <email>jjmitri@bwh.harvard.edu</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>January 26, 2019</study_first_submitted>
  <study_first_submitted_qc>February 1, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 4, 2019</study_first_posted>
  <last_update_submitted>January 5, 2023</last_update_submitted>
  <last_update_submitted_qc>January 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Brigham and Women's Hospital</investigator_affiliation>
    <investigator_full_name>Jessica Ravikoff Allegretti</investigator_full_name>
    <investigator_title>Director, Fecal Microbiota Transplantation Program</investigator_title>
  </responsible_party>
  <keyword>Crohn's DIsease</keyword>
  <keyword>Ulcerative Colitis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Clostridium Infections</mesh_term>
    <mesh_term>Intestinal Diseases</mesh_term>
    <mesh_term>Inflammatory Bowel Diseases</mesh_term>
  </condition_browse>
  <!-- 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/NCT03829475
org study id: 2018
nct id: NCT03829475
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This is a randomized controlled trial to assess the clinical and microbiological impacts of
      FMT in combination with Bezlotoxumab (bezlo) compared to FMT in combination with placebo in
      patients with both inflammatory bowel disease (IBD) a and clostridium difficile infection
      (CDI). The investigators will prospectively enroll up to 150 IBD-CDI patients from 4 tertiary
      care FMT referral centers. Patients will be randomized 1:1 to either receive FMT in
      combination with Bezlo of FMT and a placebo infusion. Donor stool from healthy donors will be
      obtained from OpenBiome. OpenBiome is a nonprofit 501(c)(3) organization that provides
      hospitals with screened, filtered, and frozen material ready for clinical use. Patients will
      be enrolled and followed prospectively for 3 months post therapy. Stool and blood samples as
      well as clinical data will be collected at baseline, week 1, 8 and 12.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Clostridium difficile recurrence
time frame: 8 weeks
description: positive test for CDI by EIA toxin
measure: Clostridium difficile recurrence
time frame: 8 weeks
description: Diarrhea defined at 3 or more bowel movements bristol 6-7 for 2 consecutive days
measure: Diarrheal symptoms
time frame: 12 weeks
description: Number of Bowel movements daily
measure: Rectal bleeding
time frame: 12 weeks
description: presence or absence of rectal bleeding
measure: Abdominal Pain
time frame: 12 weeks
description: presence of absence of abominal pain
arm group label: FMT + Bezlo
arm group type: Experimental
description: Patients in this arm will received an FMT via colonoscopy ( 250ml) as well as a single IV infusion of bezlotoxumab (10mg/kg) that will take place over 60 mins.
arm group label: FMT + Placebo
arm group type: Placebo Comparator
description: Patients in this arm will receive a single FMT via colonoscopy (250ml) and a placebo (saline) infusion (250cc) over
intervention type: Drug
intervention name: Bezlotoxumab
description: This is a a fully human monoclonal antibody that binds to C. difficile toxin B, and is indicated to prevent recurrence of CDI in adults at risk for recurrent CDI (rCDI).
arm group label: FMT + Bezlo
other name: Zinplava
intervention type: Drug
intervention name: Placebo
description: placebo is an infusion of normal saline.
arm group label: FMT + Placebo
other name: Saline
intervention type: Drug
intervention name: Fecal Microbiota Transplantation
description: FMT is an infusion of prescreened donor stool that will be administered via colonoscopy
arm group label: FMT + Bezlo
arm group label: FMT + Placebo
other name: FMT
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jennifer Mitri
phone: 6177329223
email: Jjmitri@bwh.harvard.edu
last name: Jessica Allegretti
phone: 6177326389
email: jallegretti@bwh.harvard.edu
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Brigham and Women's Hospital
investigator full name: Jessica Ravikoff Allegretti
investigator title: Director, Fecal Microbiota Transplantation Program
mesh term: Infections
mesh term: Clostridium Infections
mesh term: Intestinal Diseases
mesh term: Inflammatory Bowel Diseases