Penn Microbiome Therapy (PMT) for Severe-Clostridium Difficile Infection (CDI)

Study Overview
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Brief Summary
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This is a randomized, open label, comparative, Phase II study to determine whether fecal microbiota transplant using Penn Microbiome Therapy products helps standard therapy to treat severe Clostridium difficile infection (C diff).

Official Title
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A Phase II, Randomized Trial to Evaluate the Safety and Efficacy of Fecal Microbiota Transplantation Using the Penn Microbiome Therapy Products for Severe or Severe-Complicated/Fulminant Clostridium Difficile Infection

Conditions
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Severe Clostridium Difficile Infection, Severe-Complicated/Fulminant Clostridium Difficile Infection

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. One or more episodes of CDI with symptoms including bowel movements altered in frequency or consistency from baseline. 2. Stool test positive for Clostridium difficile by enzyme immunoassay (EIA) by FDA-cleared assay within 7 days prior to enrollment. 3. Age ≥ 18 years 4. Meets any one of the listed criteria for severe or severe-complicated/fulminant disease within 72 hours of enrollment. 5. Receiving antibiotic treatment for S/SC(Severe-complicatedcategory)/F-CDI per current Infectious Diseases Society of America(IDSA) guidelines. Enrollment criteria details: 1. Must either meet ≥1 criteria in severe category or in severe complicated category to be enrolled 2. If the subject meets criteria in both categories, stratify to the higher severity category (severe complicated) 3. Detailed enrollment criteria definitions: a. white blood cells (WBC) ≥15,000 cells/uL - if any value in the time period meets this definition b. Hypotension with systolic blood pressure sustained < 90mmHg for three or more hours or requiring vasopressors (epinephrine, norepinephrine, phenylephrine, or vasopressin) c. Acute kidney injury - increase in serum creatinine level by ≥50% or new dialysis initiation i. If a baseline serum creatinine value is not available, acute kidney injury will be defined as a serum creatinine >1.5 mg/dL d. Temperature ≥38.5 °C or <35.6°C - one value needed in time period - e. Ileus, bowel dilation or megacolon i. Ileus: If noted in any provider documentation or problem list (search words ileus) OR ii. If the words dilated dilation or ileus are noted in a radiology report on intestines/colon, or if megacolon noted f. Lactate >2.2 mmol/L - if any value in the time period meets this definition g. Systemic inflammatory response syndrome(SIRS) criteria i. Heart rate > 90 beats per minute ii. Respiratory rate > 20 breaths per minute or PaCO2 < 32 mmHg iii. Temperature >38ºC or <36ºC iv. WBC > 12,000 cells/uL, <4,000 cells/uL, or >10% immature (band) forms Exclusion Criteria: 1. Evidence of colon/small bowel perforation at the time of study screening. 2. Goals of care are directed to comfort rather than curative measures. 3. Moderate (ANC < 1000 cells/uL) or severe (ANC < 500 cells/uL) neutropenia. 4. Known food allergy that could lead to anaphylaxis. 5. 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. 6 Receipt of Fecal Microbiota Transplantation (FMT) or enrollment in a clinical trial for FMT within the last 3 months. 7 COVID-19 infection, as defined by a positive nucleic acid or antigen test within the prior 14 days and symptoms consistent with COVID-19 infection

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 |
| --- | --- |
| Active Comparator: No investigational product<br>Participants who receive the antibiotics usually prescribed for C diff infection. | Drug: Antibiotics<br>* Standard of care antibiotics<br>|
| Experimental: Upper gastrointestinal Fecal Microbiota Transplantation<br>Participants who receive the antibiotics usually prescribed for C diff infection, along with PMT that is given by mouth in capsules or through a tube that goes into your stomach/intestines if you already have one (upper delivery). You will not be assigned to this group if you cannot take any medications either by mouth or through a tube safely, as determined by your doctor | 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;Drug: Antibiotics<br>* Standard of care antibiotics<br>|
| Experimental: Lower gastrointestinal Fecal Microbiota Transplantation<br>Participants who receive the antibiotics usually prescribed for C diff infection, along with PMT that is given through the rectum by an enema (lower delivery). | Drug: Penn Microbiome Therapy - 001<br>* Fecal Microbiota for Transplant, enema product<br>* Other names: PMT-001;Drug: Antibiotics<br>* Standard of care antibiotics<br>|

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. | The outcome will be satisfied when the subject is discharged from the hospital (not to hospice or palliative care) or, while the subject remains hospitalized, when the following criteria are met for 72 hours: If radiology study or studies performed, ileus/dilation/megacolon either not noted or noted as resolved Ileus/megacolon either noted as resolved by any provider documentation or not noted White Blood Cells (WBC) <15,000 cells/uL Serum creatinine decreased, unchanged, or increased by ≤0.2 mg/dL over 72 hours (if not receiving continuous renal replacement therapy (CRRT) or hemodialysis (HD)) Lactate ≤2.2 mmol/L (if measured by clinical care team) No vasopressors used (including epinephrine, norepinephrine, phenylephrine, or vasopressin) Temperature <38.5 °C and ≥35.6°C < 8 bowel movements per day and < 600 mL unformed stool (if volume recorded) Meeting fewer than 3 systemic inflammatory response syndrome (SIRS) criteria | 3 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause Mortality at 30 Days Following Last Fecal Microbiota Transplantation (FMT) | Number of deaths within 30 days of the last FMT | 30 Days | 
| All-cause Mortality at 60-days Following Last FMT | Number of deaths within 60 days of the 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 | 
| Repeat Hospital Admission Within 60 Days of Discharge From Index Hospitalization |  | 60 Days |