Penn Microbiome Therapy for Recurrent Clostridium Difficile Infection

NCT03973697 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: IRB # 832963
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Recurrent Clostridium Difficile Infection

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• 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

Study Arms (2)

Single dose of PMT

EXPERIMENTAL

Drug: Penn Microbiome Therapy - 001; Drug: Penn Microbiome Therapy - 002; Drug: Penn Microbiome Therapy - 003

Two doses of PMT

EXPERIMENTAL

Administered within 24 hours

Drug: Penn Microbiome Therapy - 001; Drug: Penn Microbiome Therapy - 002; Drug: Penn Microbiome Therapy - 003

Interventions

Penn Microbiome Therapy - 001 DRUG

Fecal Microbiota for Transplant, enema product

Also known as: PMT-001

Single dose of PMT; Two doses of PMT

Penn Microbiome Therapy - 002 DRUG

Fecal Microbiota for Transplant, suspension product

Also known as: PMT-002

Single dose of PMT; Two doses of PMT

Penn Microbiome Therapy - 003 DRUG

Fecal Microbiota for Transplant, capsule product

Also known as: PMT-003

Single dose of PMT; Two doses of PMT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

Hospital of the Univeristy of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Clostridium Infections

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: Regulatory Lead
• Organization: University of Pennsylvania

psom-ind-ide@pobox.upenn.edu

215-662-4484

Study Officials

• Ebbing Lautenbach, MD, MPH, MSCE

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, open label, comparative

Study Record Dates

• First Submitted: April 17, 2019
• First Posted: June 4, 2019
• Study Start: January 13, 2020
• Primary Completion: August 11, 2021
• Study Completion: December 31, 2021
• Last Updated: November 1, 2023
• Results First Posted: November 1, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)