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

Study Overview
=================
Brief Summary
-----------------
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.

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

Conditions
-----------------
Inflammatory Bowel Diseases, Clostridium Difficile Infection

Intervention / Treatment
-----------------
* Drug: Bezlotoxumab
* Drug: Placebo
* Drug: Fecal Microbiota Transplantation


Participation Criteria
=================
Eligibility Criteria
-----------------
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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Crohn's DIsease, Ulcerative Colitis