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

NCT03970200 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: IRB # 832962
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Severe Clostridium Difficile Infection; Severe-Complicated/Fulminant 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.

  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 Outcomes (7)

• All-cause Mortality at 30 Days Following Last Fecal Microbiota Transplantation (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 (3)

No investigational product

ACTIVE COMPARATOR

Participants who receive the antibiotics usually prescribed for C diff infection.

Drug: Antibiotics

Upper gastrointestinal Fecal Microbiota Transplantation

EXPERIMENTAL

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; Drug: Penn Microbiome Therapy - 003; Drug: Antibiotics

Lower gastrointestinal Fecal Microbiota Transplantation

EXPERIMENTAL

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; Drug: Antibiotics

Interventions

Penn Microbiome Therapy - 001 DRUG

Fecal Microbiota for Transplant, enema product

Also known as: PMT-001

Lower gastrointestinal Fecal Microbiota Transplantation

Penn Microbiome Therapy - 002 DRUG

Fecal Microbiota for Transplant, suspension product

Also known as: PMT-002

Upper gastrointestinal Fecal Microbiota Transplantation

Penn Microbiome Therapy - 003 DRUG

Fecal Microbiota for Transplant, capsule product

Also known as: PMT-003

Upper gastrointestinal Fecal Microbiota Transplantation

Antibiotics DRUG

Standard of care antibiotics

Lower gastrointestinal Fecal Microbiota Transplantation; No investigational product; Upper gastrointestinal Fecal Microbiota Transplantation

Eligibility Criteria

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

You may qualify if:

• \. One or more episodes of CDI with symptoms including bowel movements altered in frequency or consistency from baseline.
• \. Stool test positive for Clostridium difficile by enzyme immunoassay (EIA) by FDA-cleared assay within 7 days prior to enrollment.
• \. Age ≥ 18 years
• \. Meets any one of the listed criteria for severe or severe-complicated/fulminant disease within 72 hours of enrollment.
• \. Receiving antibiotic treatment for S/SC(Severe-complicatedcategory)/F-CDI per current Infectious Diseases Society of America(IDSA) guidelines.
• Enrollment criteria details:
• \. Must either meet ≥1 criteria in severe category or in severe complicated category to be enrolled
• \. If the subject meets criteria in both categories, stratify to the higher severity category (severe complicated)
• \. 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

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.
• Receipt of Fecal Microbiota Transplantation (FMT) or enrollment in a clinical trial for FMT within the last 3 months.
• 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

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

Interventions

Anti-Bacterial Agents

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

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

  Division of Infectious Diseases, Department of Medicine, 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: May 31, 2019
• Study Start: January 16, 2020
• Primary Completion: November 21, 2021
• Study Completion: May 14, 2022
• Last Updated: October 30, 2023
• Results First Posted: October 30, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)