Hypothesis: Oral administration of hyperimmune bovine colostrum enriched with anti-LPS antibodies will reduce endotoxemia, and improve pathophysiological and clinical parameters related to severe alcoholic hepatitis (SAH). IMM 124-E is safe in subjects with severe alcoholic hepatitis being treated with steroids. Aim: To perform a phase 2a "proof of concept" placebo-controlled, dose-ranging study of Imm 124-E (hyperimmune bovine colostrum enriched with IgG anti-LPS) in subjects with severe AH on steroids.
Subjects with severe alcoholic hepatitis (20=\> MELD \<=28) about to receive prednisolone (40 mg/day x 28 days) will be randomized 1:1:1 to additionally receive either one of two doses of IMM 124-E (2400 mg/day or 4800 mg/day) orally or placebo for the same duration. Standard of care nutrition support and alcohol cessation recommendations will be provided to all subjects. Alcohol withdrawal will be managed per standard of care. Subjects who meet Lille criteria for failure of treatment on day 7 or side effects requiring discontinuation of steroids will be removed from the study. The primary endpoint is a decrease in plasma endotoxin levels. The secondary endpoints will include: 1. Mechanistic endpoints: TNF-α, immune-inflammatory markers, microbiome-metagenome 2. Efficacy-related: number of subjects meeting Lille failure criteria at day 7 , mortality (at 30 days, 90 days, and 180 days), time to drop in conjugated bilirubin by 50%, bile acids, liver function tests, change in MELD, and sequential organ failure 3. Safety related: tolerability, adverse events.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
57
Hyper-immune bovine colostrum enriched with anti-LPS antibodies and which has been designated by Immuron as IMM-124E.
Subjects will receive a total of 4 sachets (2 in the morning and 2 in the evening) daily
Indiana University
Indianapolis, Indiana, United States
Mayo Clinic
Rochester, Minnesota, United States
Virginia Commonwealth University
Richmond, Virginia, United States
Gastrointestinal Safety Endpoints
Number of events and severity of gastrointestinal events, including nausea, vomiting, and diarrhea
Time frame: 30 Days
Combined Kidney, Brain, and Lung Safety Endpoints
Number of incidents of the following: renal failure, encephalopathy or pulmonary compromise.
Time frame: 30 Days
Infection Safety Endpoints
Number of incidents of sepsis.
Time frame: 30 Days
Other Safety Endpoints
Number of incidents of all other serious adverse events and other adverse events not already assessed as a primary outcome.
Time frame: 30 Days
Bowel Gastrointestinal Safety Endpoints
Number of participants who experience diarrhea
Time frame: 30 Days
Change in Circulating Endotoxin Levels
Changes in endotoxin levels as measured using a standard blood assay
Time frame: Baseline, day 28
Lille Model Score
Number of participants who meet Lille criteria indicating failure to respond to treatment
Time frame: 7 days
Mortality
Number of deaths due to any cause
Time frame: 180 days
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Change in Liver Function
Model for end-stage liver disease (MELD) score ranges from 6 to 40 with higher number indicating worse liver function.
Time frame: 90 days
SOFA Score
SOFA is a single score based on patient status of six different biological systems: respiratory, cardiovascular, hepatic, coagulation, renal, and neurological. Scores range from 0 to 24 with higher scores indicated worse status.
Time frame: 30 days
Change in Serum Bile Acids
Serum bile acids levels as measured using standard blood serum assay
Time frame: Baseline to 90 days
Time to 50% Drop in Bilirubin
Length of time to a drop in bilirubin of 50% measured in days
Time frame: 180 days
Cytokine Data
Changes in cytokine profile across study arms at day 28
Time frame: 28 days