Back to resultsVE303 for Treatment of Hepatic Encephalopathy (HE)
Primary Purpose
Cirrhosis, Hepatic Encephalopathy
Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Placebo
VE303
oral vancomycin
Sponsored by
About this trial
This is an interventional treatment trial for Cirrhosis
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of cirrhosis based on liver biopsy, imaging, or evidence of clinical decompensation
- History of at least one episode of overt HE any time in the past
- Prescribed both lactulose and rifaximin, and compliant with this treatment
Exclusion Criteria:
- Current episode of overt HE
- Variceal bleeding in the last 4 weeks
- Gut-absorbable or intravenous antibiotic therapy in the last 28 days
- Fecal microbiota transplant in the last 6 months
- Use of probiotics in the last 2 weeks
- Alcohol or illicit drug intake in the last 4 weeks
- Primary sclerosing cholangitis as etiology of liver disease
- History of inflammatory bowel disease, short gut, gastrointestinal tract fistulas, intestinal ischemia, or any form of ongoing colitis
- Prior diagnosis of dementia or other primary neurocognitive disorder
- Known hypersensitivity/allergy/intolerance to Vancomycin and any ingredients of VE303: sucrose, histidine, yeast extract, cysteine, metabisulfite, and microcrystalline cellulose
- History of Roux-en-Y Gastric bypass
- Any gastrointestinal surgery in the last year
- Substantial immune compromise/deficiency (e.g., uncontrolled human immunodeficiency virus, active immune suppressive therapy including high doses of corticosteroids or medications to prevent graft rejection, recent myeloablative therapy, sustained neutropenia)
- Pregnancy or breast feeding
- Model for end-stage liver disease (MELD) > 20
- History of spontaneous bacterial peritonitis
- Hemodialysis in the last 28 days
- Placement of a portosystemic shunt or transjugular intrahepatic portosystemic shunt in the last 3 months (permissible if placed >3 months before enrollment)
- Unstable doses of opiates, benzodiazepines or other sedating medication
- Chronic methadone or low dose benzodiazepines (for example) is acceptable
Sites / Locations
- University of Michigan
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Placebo
VE303
Arm Description
VE303 is a live biotherapeutic product comprising 8 nonpathogenic commensal strains of Clostridia.
Outcomes
Primary Outcome Measures
Number of serious adverse events up to week 6
Change in Psychometric Hepatic Encephalopathy Score (PHES) as a measure of cognitive function from pre-vancomycin to week 6
This score is a battery of 5 paper-pencil tests that evaluate cognitive and psychomotor processing speed and visuomotor coordination. Scores on each subtest are assigned values based on age-related norms (1+ for scores better than 1 standard deviation (SD) above the normal mean to -3 for scores more than 3 SDs below the normal mean). Combined scores vary from +6 to -18.
Secondary Outcome Measures
Number of hospitalizations for overt hepatic encephalopathy (OHE) up to week 26
Adverse events up to week 26
Change in Patient Reported Outcome Measurement Information System (PROMIS) Global Health reported from pre-vancomycin to week 26
The PROMIS v 1.1 is a 10 question scale where participants select answers from (0) up to (10). Higher scores indicate better quality of life.
Time to overt HE
Change in microbiome composition from pre-vancomycin to week 26
This will be calculated by beta diversity between stool collection timepoints and will have metagenomic sequencing on stool to assess this.
Change in serum and stool biomarkers from pre-vancomycin to week 26
PHES from pre-vancomycin to week 26
This score is a battery of 5 paper-pencil tests that evaluate cognitive and psychomotor processing speed and visuomotor coordination. Scores on each subtest are assigned values based on age-related norms (1+ for scores better than 1 standard deviation (SD) above the normal mean to -3 for scores more than 3 SDs below the normal mean). Combined scores vary from +6 to -18.
Full Information
NCT ID
NCT04899115
First Posted
May 19, 2021
Last Updated
May 8, 2023
Sponsor
Patricia Bloom
Collaborators
Vedanta Biosciences, Inc., American College of Gastroenterology, American Association for the Study of Liver Diseases
1. Study Identification
Unique Protocol Identification Number
NCT04899115
Brief Title
VE303 for Treatment of Hepatic Encephalopathy (HE)
Official Title
A Randomized Controlled Trial of VE303 to Treat Hepatic Encephalopathy
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 6, 2021 (Actual)
Primary Completion Date
April 10, 2023 (Actual)
Study Completion Date
September 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Patricia Bloom
Collaborators
Vedanta Biosciences, Inc., American College of Gastroenterology, American Association for the Study of Liver Diseases
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This research is studying the use of a new drug to learn about its safety and efficacy as a treatment for hepatic encephalopathy.
Eligible participants will be enrolled and given oral antibiotics followed by 14 days of the study drug (placebo vs.VE303). There will be visits as well as other procedures to collect blood and stool samples, and have tests of your cognition (thinking) for this research study.
The hypothesis is that VE303 will safely and effectively improve cognitive function in patients with a history of overt hepatic encephalopathy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cirrhosis, Hepatic Encephalopathy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Subjects will be randomized 2:1 to VE303 vs placebo. There will be no stratification.
After the trial enrolls the first 9 patients, an interim analysis to evaluate safety of VE303 in this population will take place. If there is no concern for a higher rate of Serious adverse events (SAEs) in the VE303 group, enrollment will continue to reach a total of 18 patients.
Masking
ParticipantInvestigator
Masking Description
Study staff will remain blinded to subject randomization until the study period is over.
Allocation
Randomized
Enrollment
18 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Title
VE303
Arm Type
Experimental
Arm Description
VE303 is a live biotherapeutic product comprising 8 nonpathogenic commensal strains of Clostridia.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Starting the last day of oral vancomycin (Day 1), subjects randomized to this arm will take 5 capsules of placebo for 14 days taken once daily.
Intervention Type
Drug
Intervention Name(s)
VE303
Intervention Description
Starting the last day of oral vancomycin (Day 1), subjects randomized to this arm will take 5 capsules of VE303 taken daily for 14 days.
The quantity of each strain is proportioned to assure a specific per-strain per-capsule titer. The 8 strains are blended together with a micro-crystalline cellulose flow agent and placed in enteric capsules.
Intervention Type
Drug
Intervention Name(s)
oral vancomycin
Intervention Description
All enrolled subjects will receive 5 days of oral vancomycin 125 mg four times a day (q.i.d).
Primary Outcome Measure Information:
Title
Number of serious adverse events up to week 6
Time Frame
Week 6
Title
Change in Psychometric Hepatic Encephalopathy Score (PHES) as a measure of cognitive function from pre-vancomycin to week 6
Description
This score is a battery of 5 paper-pencil tests that evaluate cognitive and psychomotor processing speed and visuomotor coordination. Scores on each subtest are assigned values based on age-related norms (1+ for scores better than 1 standard deviation (SD) above the normal mean to -3 for scores more than 3 SDs below the normal mean). Combined scores vary from +6 to -18.
Time Frame
baseline (pre-vancomycin), Week 6
Secondary Outcome Measure Information:
Title
Number of hospitalizations for overt hepatic encephalopathy (OHE) up to week 26
Time Frame
up to week 26
Title
Adverse events up to week 26
Time Frame
up to week 26
Title
Change in Patient Reported Outcome Measurement Information System (PROMIS) Global Health reported from pre-vancomycin to week 26
Description
The PROMIS v 1.1 is a 10 question scale where participants select answers from (0) up to (10). Higher scores indicate better quality of life.
Time Frame
baseline (pre-vancomycin), week 26
Title
Time to overt HE
Time Frame
up to 26 weeks
Title
Change in microbiome composition from pre-vancomycin to week 26
Description
This will be calculated by beta diversity between stool collection timepoints and will have metagenomic sequencing on stool to assess this.
Time Frame
baseline (pre-vancomycin), week 26
Title
Change in serum and stool biomarkers from pre-vancomycin to week 26
Time Frame
baseline (pre-vancomycin), week 26
Title
PHES from pre-vancomycin to week 26
Description
This score is a battery of 5 paper-pencil tests that evaluate cognitive and psychomotor processing speed and visuomotor coordination. Scores on each subtest are assigned values based on age-related norms (1+ for scores better than 1 standard deviation (SD) above the normal mean to -3 for scores more than 3 SDs below the normal mean). Combined scores vary from +6 to -18.
Time Frame
pre-vancomycin up to week 26
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of cirrhosis based on liver biopsy, imaging, or evidence of clinical decompensation
History of at least one episode of overt HE any time in the past
Prescribed both lactulose and rifaximin, and compliant with this treatment
Exclusion Criteria:
Current episode of overt HE
Variceal bleeding in the last 4 weeks
Gut-absorbable or intravenous antibiotic therapy in the last 28 days
Fecal microbiota transplant in the last 6 months
Use of probiotics in the last 2 weeks
Alcohol or illicit drug intake in the last 4 weeks
Primary sclerosing cholangitis as etiology of liver disease
History of inflammatory bowel disease, short gut, gastrointestinal tract fistulas, intestinal ischemia, or any form of ongoing colitis
Prior diagnosis of dementia or other primary neurocognitive disorder
Known hypersensitivity/allergy/intolerance to Vancomycin and any ingredients of VE303: sucrose, histidine, yeast extract, cysteine, metabisulfite, and microcrystalline cellulose
History of Roux-en-Y Gastric bypass
Any gastrointestinal surgery in the last year
Substantial immune compromise/deficiency (e.g., uncontrolled human immunodeficiency virus, active immune suppressive therapy including high doses of corticosteroids or medications to prevent graft rejection, recent myeloablative therapy, sustained neutropenia)
Pregnancy or breast feeding
Model for end-stage liver disease (MELD) > 20
History of spontaneous bacterial peritonitis
Hemodialysis in the last 28 days
Placement of a portosystemic shunt or transjugular intrahepatic portosystemic shunt in the last 3 months (permissible if placed >3 months before enrollment)
Unstable doses of opiates, benzodiazepines or other sedating medication
Chronic methadone or low dose benzodiazepines (for example) is acceptable
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patricia Bloom, MD
Organizational Affiliation
University of Michigan
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
VE303 for Treatment of Hepatic Encephalopathy (HE)
We'll reach out to this number within 24 hrs