VE303 for Treatment of Hepatic Encephalopathy (HE)

NCT04899115 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: HUM00194437
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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.

Conditions

Cirrhosis; Hepatic Encephalopathy

Outcome Measures

Primary Outcomes (2)

• Number of Participants Who Experienced Serious Adverse Events up to Week 6

  An adverse event (AE) or suspected adverse reaction is considered "serious" if, in the view of the investigator, it results in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.

  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, where +6 is the best function and -18 is worst function.

  baseline (pre-vancomycin), Week 6

Secondary Outcomes (6)

• Number of Hospitalizations for Overt Hepatic Encephalopathy (OHE) up to Week 26

  26 weeks

• 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

  baseline (pre-vancomycin), week 26

• Time to Overt HE

  up to 26 weeks

• Change in Microbiome Composition From Pre-vancomycin to Week 26

  baseline (pre-vancomycin), week 26

Other Outcomes (1)

• Change in Serum and Stool Biomarkers From Pre-vancomycin to Week 26

  baseline (pre-vancomycin), week 26

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Drug: Placebo; Drug: oral vancomycin

VE303

EXPERIMENTAL

VE303 is a live biotherapeutic product comprising 8 nonpathogenic commensal strains of Clostridia.

Drug: VE303; Drug: oral vancomycin

Interventions

Placebo DRUG

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.

Placebo

VE303 DRUG

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.

VE303

oral vancomycin DRUG

All enrolled subjects will receive 5 days of oral vancomycin 125 mg four times a day (q.i.d).

Placebo; VE303

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Patricia Bloom: lead
• Vedanta Biosciences, Inc.: collaborator
• American College of Gastroenterology: collaborator
• American Association for the Study of Liver Diseases: collaborator

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Fibrosis; Hepatic Encephalopathy

Interventions

Vancomycin

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins

Limitations and Caveats

Note that for PHES and some other outcome measures, the drop out rate was high.

Results Point of Contact

• Title: Patricia Bloom, MD
• Organization: University of Michigan

ppbloom@med.umich.edu

734-647-5944

Study Officials

• Patricia Bloom, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Study staff will remain blinded to subject randomization until the study period is over.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Lecturer in Internal Medicine

Model Details: 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.

Study Record Dates

• First Submitted: May 19, 2021
• First Posted: May 24, 2021
• Study Start: August 6, 2021
• Primary Completion: April 10, 2023
• Study Completion: August 30, 2023
• Last Updated: February 7, 2025
• Results First Posted: May 7, 2024

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)