VE303 for Treatment of Hepatic Encephalopathy (HE)

Patricia Bloom

Status and phase: Completed; Phase 2

Conditions: Hepatic Encephalopathy; Cirrhosis

Treatments: Drug: Placebo; Drug: VE303; Drug: oral vancomycin

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04899115

HUM00194437

Details and patient eligibility

About

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.

Enrollment: 19 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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19 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Treatment:

Drug: oral vancomycin

Drug: Placebo

VE303

Experimental group

Description:

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

Treatment:

Drug: oral vancomycin

Drug: VE303