VE303 for Treatment of Hepatic Encephalopathy (HE)

A Randomized Controlled Trial of VE303 to Treat Hepatic Encephalopathy

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Hepatic Encephalopathy; Cirrhosis
• Intervention / Treatment: Drug: Placebo; Drug: oral vancomycin; Drug: VE303

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Haila Asefa; Phone Number: 734-232-0284; Email: asefah@med.umich.edu
• Study Contact Backup: Name: Patricia Bloom, MD; Phone Number: 734-647-9252; Email: ppbloom@umich.edu

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; 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.; Drug: oral vancomycin; All enrolled subjects will receive 5 days of oral vancomycin 125 mg four times a day (q.i.d).
Experimental: VE303; VE303 is a live biotherapeutic product comprising 8 nonpathogenic commensal strains of Clostridia.	Drug: oral vancomycin; All enrolled subjects will receive 5 days of oral vancomycin 125 mg four times a day (q.i.d).; Drug: VE303; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of serious adverse events up to week 6		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.	baseline (pre-vancomycin), Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of hospitalizations for overt hepatic encephalopathy (OHE) up to week 26		up to week 26
Adverse events up to week 26		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.	baseline (pre-vancomycin), week 26
Time to overt HE		up to 26 weeks
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.	baseline (pre-vancomycin), week 26
Change in serum and stool biomarkers from pre-vancomycin to week 26		baseline (pre-vancomycin), 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.	pre-vancomycin up to week 26

Collaborators and Investigators

• Sponsor: Patricia Bloom
• Collaborators: American College of Gastroenterology; American Association for the Study of Liver Diseases; Vedanta Biosciences, Inc.
• Investigators: Principal Investigator: Patricia Bloom, MD, University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): August 6, 2021
• Primary Completion (Actual): April 10, 2023
• Study Completion (Anticipated): September 1, 2023

Study Registration Dates

• First Submitted: May 19, 2021
• First Submitted That Met QC Criteria: May 19, 2021
• First Posted (Actual): May 24, 2021

Study Record Updates

• Last Update Posted (Actual): May 10, 2023
• Last Update Submitted That Met QC Criteria: May 8, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Liver Diseases; Brain Diseases, Metabolic; Hepatic Encephalopathy; Brain Diseases; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin
• Other Study ID Numbers: HUM00194437

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No