Penn Microbiome Therapy for Recurrent Clostridium Difficile Infection

Study Overview
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Brief Summary
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This is a randomized, open label, comparative, Phase II study to determine which dose of fecal microbiota transplant using Penn Microbiome Therapy (PMT) products is most effective in treating and preventing recurrence of Clostridium difficile infection (C diff).

Official Title
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A Phase II, Randomized Trial to Evaluate the Optimal Dosing of Fecal Microbiota Transplantation Using the Penn Microbiome Therapy Products for Recurrent Clostridium Difficile Infection

Conditions
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Recurrent Clostridium Difficile Infection

Intervention / Treatment
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* Drug: Penn Microbiome Therapy - 001
* Drug: Penn Microbiome Therapy - 002
* Drug: Penn Microbiome Therapy - 003


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Second or greater episode of CDI (first or greater recurrence) within 12 months, with symptoms including bowel movement altered in frequency or consistency from baseline. Stool positive for C. difficile toxin by EIA or toxin gene by NAAT within 60 days of enrollment. At least one additional prior positive stool test for C. difficile within the prior 12 months (EIA or NAAT as above). Age ≥ 18 years. Minimum of 72 hours of receipt of standard-of-care (vancomycin or fidaxomicin) antibiotic treatment for R-CDI prior to intervention. Exclusion Criteria: Evidence of colon/small bowel perforation at the time of study screening Goals of care are directed to comfort rather than curative measures. Moderate (ANC < 1000 cells/uL) or severe (ANC < 500 cells/uL) neutropenia. Known food allergy that could lead to anaphylaxis. Pregnancy a. For subjects of childbearing potential (ages 18 to 55), the subject must have a negative urine pregnancy test within 48 hours of consent and no more than 48 hours prior to first product administration Meeting criteria for severe, severe-complicated/fulminant CDI within 24 hours of planned trial enrollment. We define severe or severe-complicated/fulminant CDI as any one of the following: (1) leukocytosis with peripheral WBC ≥ 15,000 cells/mL; (2) hypotension with systolic blood pressure sustained < 90mmHg for three or more hours or requiring pressors; (3) provider documentation of ileus or radiologic evidence of bowel dilation or megacolon; (4) acute kidney injury with increase in baseline serum creatinine level by ≥50% or new dialysis initiation; (5) serum lactate > 2.2 mmol/L; or (6) ≥ 3 systemic inflammatory response syndrome (SIRS) criteria (which include heart rate > 90 beats per minute, respiratory rate > 20 breaths per minute or PaCO2 < 32 mmHg, temperature >38ºC or <36ºC, WBC > 12,000 cells/uL, <4,000 cells/uL, or >10% immature (band) forms). Receipt of FMT or enrollment in a clinical trial for FMT within the last 3 months.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, open label, comparative
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single dose of PMT<br> | Drug: Penn Microbiome Therapy - 001<br>* Fecal Microbiota for Transplant, enema product<br>* Other names: PMT-001;Drug: Penn Microbiome Therapy - 002<br>* Fecal Microbiota for Transplant, suspension product<br>* Other names: PMT-002;Drug: Penn Microbiome Therapy - 003<br>* Fecal Microbiota for Transplant, capsule product<br>* Other names: PMT-003;|
| Experimental: Two doses of PMT<br>Administered within 24 hours | Drug: Penn Microbiome Therapy - 001<br>* Fecal Microbiota for Transplant, enema product<br>* Other names: PMT-001;Drug: Penn Microbiome Therapy - 002<br>* Fecal Microbiota for Transplant, suspension product<br>* Other names: PMT-002;Drug: Penn Microbiome Therapy - 003<br>* Fecal Microbiota for Transplant, capsule product<br>* Other names: PMT-003;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Resolution of Symptoms After Treatment With One of the PMT Suite of Products or Control. | Clinical resolution will be compared by determining the proportion of subjects with clinical resolution of diarrhea without recurrence in subjects with R-CDI at 8 weeks (56 days) following FMT. Clinical resolution will be defined as follows: ≤ 4 stools per calendar day for the prior two days with no stool of Bristol stool scale type 7 No additional stool tests with a positive EIA for C. difficile toxin since study enrollment No additional prescription or use of anti-CDI antibiotics (unless given for prophylaxis) since study enrollment No need for an additional | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause Mortality at 30-days Following Last FMT |  | 30 days | 
| All-cause Mortality at 60-days Following Last FMT |  | 60 days | 
| Colectomy or Diverting Ileostomy Within 30 Days After Last FMT |  | 30 days | 
| Cumulative Days of Hospitalization From Enrollment Until 30 Days After FMT |  | 30 days | 
| Cumulative Days in Intensive Care Unit From Enrollment Until 30 Days After Last FMT |  | 30 Days | 
| Bacteremia From Enrollment Until 30 Days After Last FMT |  | 30 days | 
| Hospital Admission Within 60 Days of Discharge From Index Hospitalization |  | 60 days |