ICON-2: FMT and Bezlotoxumab Compared to FMT and Placebo for Patients With IBD and CDI (ICON-2)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Inflammatory Bowel Diseases; Clostridium Difficile Infection
• Intervention / Treatment: Drug: Bezlotoxumab; Drug: Fecal Microbiota Transplantation; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jessica Allegretti; Phone Number: 6177326389; Email: jallegretti@bwh.harvard.edu
• Study Contact Backup: Name: Emma McClure; Phone Number: 6175257322; Email: elmcclure@bwh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults age 18 or greater
• History of ≥ 2 episodes of recurrent CDI. CDI is defined as the presence of diarrhea ( Bristol 6 or 7 for 48 hours and a confirmatory test for CDI). Preferred testing will be a two-step method using GDH/EIA toxin, though PCR will be accepted based on hospital availability with confirmation of the most recent episode occurring within the prior 3 months
• Confirmed diagnosis of IBD (ulcerative colitis, Crohn's disease or indeterminate colitis)
• Undergoing FMT via colonoscopy for CDI as part of standard medical care

Exclusion Criteria:

• Unable or unwilling to undergo a colonoscopy
• Inpatient status, though patients can be screened while inpatients, the must be outpatient for the planned colonoscopy.
• Anticipated immediate or upcoming surgery within 30 days
• Need for continued non-anti-CDI antibiotic therapy
• History of total proctocolectomy
• Female patients who are pregnant or breastfeeding or plan to become pregnant in the next 6 months.
• Patients who are unable to give informed consent
• Participation in a clinical trial in the preceding 30 days or simultaneously during this trial
• Severe food allergy (anaphylaxis or anaphylactoid-like reaction)
• Life expectancy < 6 months
• Unable to adhere to protocol requirements
• Patient who have received an FMT in the past year
• Any condition that the physician investigators deems unsafe, including other conditions or medications that the investigator determines that it will put the subject at greater risk from FMT
• Patient who is diagnosed with NYHA class 3 or 4 Heart Failure
• Lab value of WBC <3.0 x 103/mm3 , Platelets <100 x 103/mm3 , ALT or AST > 1.5 x institutional ULN
• EBV or CMV negative if a patient is severely immunosuppressed ( defined as 3 or more immunosuppressing agents)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FMT + Bezlo; 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.	Drug: Bezlotoxumab; 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).; Other Names: Zinplava; Drug: Fecal Microbiota Transplantation; FMT is an infusion of prescreened donor stool that will be administered via colonoscopy; Other Names: FMT
Placebo Comparator: FMT + Placebo; Patients in this arm will receive a single FMT via colonoscopy (250ml) and a placebo (saline) infusion (250cc) over	Drug: Fecal Microbiota Transplantation; FMT is an infusion of prescreened donor stool that will be administered via colonoscopy; Other Names: FMT; Drug: Placebo; placebo is an infusion of normal saline.; Other Names: Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clostridium difficile recurrence	positive test for CDI by EIA toxin	8 weeks
Clostridium difficile recurrence	Diarrhea defined at 3 or more bowel movements bristol 6-7 for 2 consecutive days	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diarrheal symptoms	Number of Bowel movements daily	12 weeks
Rectal bleeding	presence or absence of rectal bleeding	12 weeks
Abdominal Pain	presence of absence of abominal pain	12 weeks

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Estimated): February 1, 2024
• Study Completion (Estimated): March 1, 2024

Study Registration Dates

• First Submitted: January 26, 2019
• First Submitted That Met QC Criteria: February 1, 2019
• First Posted (Actual): February 4, 2019

Study Record Updates

• Last Update Posted (Estimated): January 26, 2024
• Last Update Submitted That Met QC Criteria: January 25, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Ulcerative Colitis; Crohn's DIsease
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Infections; Inflammatory Bowel Diseases; Intestinal Diseases; Clostridium Infections
• Other Study ID Numbers: 2018

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No