PMT for Severe-CDI

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03970200
• Collaborator: (none)
• Enrollment: 15
• Location: 1
• Arms: 3
• Anticipated Duration (Months): 29.5
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Severe Clostridium Difficile Infection; Severe-Complicated/Fulminant Clostridium Difficile Infection	Drug: Penn Microbiome Therapy - 001; Drug: Penn Microbiome Therapy - 002; Drug: Penn Microbiome Therapy - 003; Drug: Antibiotics	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized, open label, comparativeRandomized, open label, comparative
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Jan 16, 2020
• Actual Primary Completion Date: Nov 21, 2021
• Anticipated Study Completion Date: Jul 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: No investigational product Participants who receive the antibiotics usually prescribed for C diff infection.	Drug: Antibiotics; Standard of care antibiotics
Experimental: Upper gastrointestinal FMT 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; 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: Antibiotics; Standard of care antibiotics
Experimental: Lower gastrointestinal FMT 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; Fecal Microbiota for Transplant, enema product; Other Names: PMT-001 ; Drug: Antibiotics; Standard of care antibiotics

Outcome Measures

Primary Outcome Measures

1. Number of subjects with resolution of symptoms after treatment with one of the PMT suite of products. [7 Days]

   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 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

Secondary Outcome Measures

1. Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE V5.0 [180 Days]

   All-cause mortality at 30- and 60-days following last FMT Colectomy or diverting ileostomy within 30 days after last FMT Cumulative days of hospitalization from enrollment until 30 days after FMT Cumulative days in intensive care unit from enrollment until 30 days after last FMT Bacteremia from enrollment until 30 days after last FMT Repeat hospital admission within 60 days of discharge from index hospitalization

2. Frequency solicited adverse events (AEs) as assessed by CTCAE V5.0 [180 Days]

3. Frequency serious adverse events (SAEs) as assessed by CTCAE V5.0 [180 Days]

4. Frequency of AEs of special interest (AESIs) as assessed by CTCAE V5.0 [180 Days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 1. One or more episodes of CDI with symptoms including bowel movements altered in frequency or consistency from baseline.
• 1. Stool test positive for Clostridium difficile by EIA by FDA-cleared assay within 7 days prior to enrollment.
• 1. Age ≥ 18 years
• 1. Meets any one of the listed criteria for severe or severe-complicated/fulminant disease within 72 hours of enrollment.
• 1. Receiving antibiotic treatment for S/SC/F-CDI per current IDSA guidelines.

Enrollment criteria details:

• 1. Must either meet ≥1 criteria in severe category or in severe complicated category to be enrolled
• 1. If the subject meets criteria in both categories, stratify to the higher severity category (severe complicated)
• 1. Detailed enrollment criteria definitions:
• 1. WBC ≥15,000 cells/uL - if any value in the time period meets this definition
• 1. Hypotension with systolic blood pressure sustained < 90mmHg for three or more hours or requiring vasopressors (epinephrine, norepinephrine, phenylephrine, or vasopressin)
• 1. Acute kidney injury - increase in serum creatinine level by ≥50% or new dialysis initiation
• 1. If a baseline serum creatinine value is not available, acute kidney injury will be defined as a serum creatinine >1.5 mg/dL
• 1. Temperature ≥38.5 °C or <35.6°C - one value needed in time period -
• 1. Ileus, bowel dilation or megacolon
• 1. Ileus: If noted in any provider documentation or problem list (search words "ileus") OR
• 1. If the words "dilated" "dilation" or "ileus" are noted in a radiology report on intestines/colon, or if "megacolon" noted
• 1. Lactate >2.2 mmol/L - if any value in the time period meets this definition
• 1. SIRS criteria
• 1. Heart rate > 90 beats per minute
• 1. Respiratory rate > 20 breaths per minute or PaCO2 < 32 mmHg
• 1. Temperature >38ºC or <36ºC
• 1. 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.
• 1. Goals of care are directed to comfort rather than curative measures.
• 1. Moderate (ANC < 1000 cells/uL) or severe (ANC < 500 cells/uL) neutropenia.
• 1. Known food allergy that could lead to anaphylaxis.
• 1. Pregnancy
• 1. 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 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital of the Univeristy of Pennsylvania	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• University of Pennsylvania

Investigators

• Principal Investigator: Ebbing Lautenbach, MD, MPH, MSCE, Division of Infectious Diseases, Department of Medicine, University of Pennsylvania

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT03970200
• Other Study ID Numbers: IRB # 832962
• First Posted: May 31, 2019
• Last Update Posted: Jan 21, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Infections; Communicable Diseases; Clostridium Infections; Anti-Bacterial Agents

Study Results

No Results Posted as of Jan 21, 2022