Clinical trial NCT04899115: VE303 for Treatment of Hepatic Encephalopathy (HE)
Official title: A Randomized Controlled Trial of VE303 to Treat Hepatic Encephalopathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cirrhosis
Hepatic Encephalopathy
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: Vedanta Biosciences, Inc.
name: American College of Gastroenterology
name: American Association for the Study of Liver Diseases
First posted: 2021-05-24
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Participants Who Experienced Serious Adverse Events up to Week 6
timeFrame: Week 6
measure: Change in Psychometric Hepatic Encephalopathy Score (PHES) as a Measure of Cognitive Function From Pre-vancomycin to Week 6
timeFrame: baseline (pre-vancomycin), Week 6
Secondary outcomes:
measure: Number of Hospitalizations for Overt Hepatic Encephalopathy (OHE) up to Week 26
timeFrame: 26 weeks
measure: Adverse Events up to Week 26
timeFrame: up to week 26
measure: Change in Patient Reported Outcome Measurement Information System (PROMIS) Global Health Reported From Pre-vancomycin to Week 26
timeFrame: baseline (pre-vancomycin), week 26
measure: Time to Overt HE
timeFrame: up to 26 weeks
measure: Change in Microbiome Composition From Pre-vancomycin to Week 26
timeFrame: baseline (pre-vancomycin), week 26
measure: PHES From Pre-vancomycin to Week 26
timeFrame: pre-vancomycin up to week 26
Other outcomes:
measure: Change in Serum and Stool Biomarkers From Pre-vancomycin to Week 26
timeFrame: baseline (pre-vancomycin), week 26
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
affiliation: University of Michigan
name: Patricia Bloom, MD
role: PRINCIPAL_INVESTIGATOR
References: