PMT for Severe-CDI

• ClinicalTrials.gov Identifier: NCT03970200
• Recruitment Status: Terminated
• First Posted: May 31, 2019
• Last Update Posted: January 30, 2023
• Sponsor: University of Pennsylvania
• Information provided by (Responsible Party): University of Pennsylvania

Tracking Information

• First Submitted Date: April 17, 2019
• First Posted Date: May 31, 2019
• Last Update Posted Date: January 30, 2023
• Actual Study Start Date: January 16, 2020
• Actual Primary Completion Date: November 21, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 23, 2021)

Number of subjects with resolution of symptoms after treatment with one of the PMT suite of products. [ Time Frame: 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

Original Primary Outcome Measures (submitted: May 29, 2019)

Number of subjects with resolution of symptoms after treatment with one of the PMT suite of products. [ Time Frame: 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 24 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 24 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

Current Secondary Outcome Measures (submitted: May 29, 2019)

• Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE V5.0 [ Time Frame: 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
• Frequency solicited adverse events (AEs) as assessed by CTCAE V5.0 [ Time Frame: 180 Days ]
• Frequency serious adverse events (SAEs) as assessed by CTCAE V5.0 [ Time Frame: 180 Days ]
• Frequency of AEs of special interest (AESIs) as assessed by CTCAE V5.0 [ Time Frame: 180 Days ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: PMT for Severe-CDI
• 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
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Randomized, open label, comparative

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Severe Clostridium Difficile Infection
• Severe-Complicated/Fulminant Clostridium Difficile Infection

Intervention

• Drug: Penn Microbiome Therapy - 001
  Fecal Microbiota for Transplant, enema product
  Other Name: PMT-001
• Drug: Penn Microbiome Therapy - 002
  Fecal Microbiota for Transplant, suspension product
  Other Name: PMT-002
• Drug: Penn Microbiome Therapy - 003
  Fecal Microbiota for Transplant, capsule product
  Other Name: PMT-003
• Drug: Antibiotics
  Standard of care antibiotics

Study Arms

• Active Comparator: No investigational product
  Participants who receive the antibiotics usually prescribed for C diff infection.
  Intervention: Drug: Antibiotics
• Experimental: Upper gastrointestinal Fecal Microbiota Transplantation
  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
  Interventions:

  • Drug: Penn Microbiome Therapy - 002
  • Drug: Penn Microbiome Therapy - 003
  • Drug: Antibiotics
• Experimental: Lower gastrointestinal Fecal Microbiota Transplantation
  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).
  Interventions:

  • Drug: Penn Microbiome Therapy - 001
  • Drug: Antibiotics

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: January 19, 2022): 15
• Original Estimated Enrollment (submitted: May 29, 2019): 90
• Actual Study Completion Date: May 14, 2022
• Actual Primary Completion Date: November 21, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 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/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
• 2. If the subject meets criteria in both categories, stratify to the higher severity category (severe complicated)
• 3. Detailed enrollment criteria definitions:
• a. 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. 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 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03970200
• Other Study ID Numbers: IRB # 832962
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: University of Pennsylvania
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Pennsylvania
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: University of Pennsylvania
• Verification Date: January 2023