Penn Microbiome Therapy for Recurrent Clostridium Difficile Infection

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

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).

Study Overview

• Status: Terminated
• Conditions: Recurrent Clostridium Difficile Infection
• Intervention / Treatment: Drug: Penn Microbiome Therapy - 002; Drug: Penn Microbiome Therapy - 003; Drug: Penn Microbiome Therapy - 001

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the Univeristy of Pennsylvania

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. 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.
2. Stool positive for C. difficile toxin by EIA or toxin gene by NAAT within 60 days of enrollment.
3. At least one additional prior positive stool test for C. difficile within the prior 12 months (EIA or NAAT as above).
4. Age ≥ 18 years.
5. Minimum of 72 hours of receipt of standard-of-care (vancomycin or fidaxomicin) antibiotic treatment for R-CDI prior to intervention.

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. 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).
7. Receipt of FMT or enrollment in a clinical trial for FMT within the last 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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	Time Frame
Cumulative Days in Intensive Care Unit From Enrollment Until 30 Days After Last FMT	30 Days
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
Bacteremia From Enrollment Until 30 Days After Last FMT	30 days
Hospital Admission Within 60 Days of Discharge From Index Hospitalization	60 days

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Ebbing Lautenbach, MD, MPH, MSCE, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2020
• Primary Completion (Actual): August 11, 2021
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: April 17, 2019
• First Submitted That Met QC Criteria: June 3, 2019
• First Posted (Actual): June 4, 2019

Study Record Updates

• Last Update Posted (Actual): November 1, 2023
• Last Update Submitted That Met QC Criteria: October 6, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Infections; Communicable Diseases; Recurrence; Clostridium Infections
• Other Study ID Numbers: IRB # 832963

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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