A Trial of Encapsulated Fecal Microbiota for Vancomycin Resistant Enterococcus Decolonization

Study Overview
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Brief Summary
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The objective of this study is to provide preliminary insight into the safety and efficacy of fecal microbiota transplantation (FMT) for the eradication of gastrointestinal carriage of vancomycin-resistant Enterococcus.

Detailed Description
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Note: The Protocol and Statistical Analysis Plan document contains modifications from what is on file at the FDA to reflect redactions and formatting requirements for public posting on ClinicalTrials.gov.

Official Title
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Phase II Randomized, Double Blind, Placebo-controlled, Parallel Group Trial of Encapsulated Fecal Microbiota Transplantation for Vancomycin Resistant Enterococcus Decolonization

Conditions
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Antibiotic Resistant Strain

Intervention / Treatment
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* Biological: Encapsulated fecal microbiota preparation
* Biological: Encapsulated placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults 18 years or older at the time of enrollment. Able to provide signed and dated informed consent. Identified as VRE-positive by a stool culture within last 14 days. Women of childbearing potential in sexual relationships with men must use an acceptable method of contraception§ from 30 days prior to enrollment until 4 weeks after completing study treatment. Males must agree to avoid impregnation of women during and for four weeks after completing study treatment through use of an acceptable method of contraception*. Includes, but is not limited to, barrier with additional spermicidal foam or jelly, intrauterine device, hormonal contraception (started at least 30 days prior to study enrollment), intercourse with men who underwent vasectomy. Includes, but is not limited to, barrier with additional spermicidal foam or jelly and vasectomy. Exclusion Criteria: Female patient who are pregnant, lactating or planning on becoming pregnant during study. Female patients of childbearing potential will undergo a pregnancy test, and be excluded from the study if positive. Inability (e.g. dysphagia) to or unwilling to swallow capsules. Active antibiotic resistant bacteria (ARB) or gastrointestinal infection at time of enrollment. Patient received antibiotics in the last 48 hours. Patients will be eligible to enroll if antibiotic therapy is discontinued for at minimum 48 hours prior to randomization. Does not include antibiotics used for prophylaxis or topical antibiotics. Requires continued antibiotic use or anticipates antibiotic use in the upcoming 4 weeks. Does not include antibiotics used for prophylaxis or topical antibiotics. Unwilling to withhold probiotics for a minimum of 48 hours prior to providing a screening stool sample. Known or suspected toxic megacolon and/or known small bowel ileus. Major gastrointestinal surgery (e.g. significant bowel resection) within 3 months before enrollment. This does not include appendectomy or cholecystectomy. History of total colectomy or bariatric surgery. Admitted to or expected to an intensive care unit for medical reasons (not just boarding). Patients residing in a nursing home, long-term care facility or rehabilitation center may be enrolled. Concurrent intensive induction chemotherapy, radiation therapy or biological treatment for active malignancy. Patients on maintenance chemotherapy may be enrolled only after consultation with medical monitor. Unable or unwilling to comply with protocol requirements. Expected life expectancy < 6 months Previous FMT or microbiome-based products at any time excluding this study. Patients with a history of severe anaphylactic or anaphylactoid food allergy. Solid organ transplant recipients ≤ 90 days post-transplant or on active treatment for rejection. Neutropenia (≤500 neutrophils/mL) or other severe immunosuppression. Anti-TNF will be permitted. Patients on monoclonal antibodies to B and T cells. glucocorticoids, antimetabolites (azathioprine, 6-mercaptopurine, methotrexate), calcineurin inhibitors (tacrolimus, cyclosporine) and mycophenolate mofetil may be enrolled only after consultation with the medical monitor. If at risk for CMV/EBV associated disease (at investigator's discretion, e.g. immunocompromised), negative IgG testing for cytomegalovirus (CMV) or Epstein Barr Virus (EBV). A condition that would jeopardize the safety or rights of the subject, would make it unlikely for the subject to complete the study, or would confound the results of the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active: Encapsulated Fecal Microbiota Preparation<br>Single dose of oral, encapsulated fecal microbiota preparation (30 capsules per dose) with follow-up at 3 days, 10 days, 28 days, and 6 months. | Biological: Encapsulated fecal microbiota preparation<br>* 30 capsules<br>|
| Placebo Comparator: Placebo: Encapsulated Placebo<br>Single dose of oral, placebo capsule (30 capsules per dose) with follow-up at 3 days, 10 days, and 28 days, and 6 months. | Biological: Encapsulated placebo<br>* 30 capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With VRE Decolonization | VRE decolonization is defined by absence of VRE on stool culture using standard clinical laboratory techniques at Day 10 (± 3 days) after randomization. | Day 10 (±3 days) after randomization | 
| Percentage of Participants With an Adverse Event (AE); Severe Adverse Event (SAE); and Newly Acquired Transmissible Infectious Diseases Which Are Considered Adverse Events of Special Interest (AESI) | Percentage of participants with an adverse event (AE); severe adverse event (SAE); and newly acquired transmissible infectious diseases which are considered adverse events of special interest (AESI) through Day 10 (± 3 days) after randomization. | Day 10 (±3 days) after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With VRE Infection | Percentage of participants with VRE infection, defined as an associated bacteremia, urinary tract infection, or wound-related infection. | Week 4 (±5 days) after randomization | 
| Percentage of Participants With ARB Colonization on Day 10 Following Fecal Microbiota Transplantation (FMT) | Percentage of participants with other antibiotic resistant bacteria (ARB) colonization | Day 10 (± 3 days) after randomization | 
| Percentage of Participants With ARB Infection 4 Weeks Following FMT | Percentage of participants with composite ARB infection | Week 4 (±5 days) after randomization | 
| Number of Days Between FMT and VRE Colonization and Infection Occurs | Time (in days) from randomization until the study day when VRE colonization and infection occurs | Up to 6 months after randomization | 
| VRE Decolonization Among Immunocompromised Patients | Percentage of participants with VRE decolonization among immunocompromised patients | Day 10 (± 3 days) after randomization | 
| Adverse Events Within 4 Weeks Following FMT | Percentage of participants with an adverse event (AE) | Week 4 (±5 days) after randomization | 
| Serious Adverse Events Within 4 Weeks Following FMT | Percentage of participants with a serious adverse event (SAE) | Week 4 (±5 days) after randomization | 
| Newly Acquired Transmissible Infectious Diseases Which Are Considered Adverse Events of Special Interest (AESI) | Percentage of participants with newly acquired transmissible infectious diseases which are considered adverse events of special interest (AESI) | Week 4 (±5 days) after randomization | 
| Serious Adverse Events Within 6 Months Following FMT | Percentage of participants with a Serious Adverse Event (SAE) | Month 6 (±14 days) phone safety assessment after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vancomycin resistant enterococcus, VRE, decolonization, VRE colonization, fecal microbiota transplantation, FMT, FMT capsule, capsule, antimicrobial resistance, antibiotic resistance, MDRO, multidrug-resistant organism, OpenBiome