Safety and Efficacy of IMM 124-E for Patients With Severe Alcoholic Hepatitis

Phase 2

Completed

Interventions: Drug: IMM 124-E (Hyperimmune Bovine Colostrum)
Drug: Placebo (High protein milk powder)

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Inclusion Criteria

Alcoholic hepatitis
Men and women age 21 and above
MELD >= 20 but <=28
About to initiate prednisolone treatment, < 7 days of steroid treatment, or treatment naive.
Actively consuming alcohol within 6 weeks of entry into the study
Willing and able to comply with study requirements (including contraception)
Subjects or their legally authorized representative (LAR) who have provided voluntary written informed consent.

Exclusion Criteria

Failure to obtain informed consent
Subjects who are known to be HIV positive
Active infection or sepsis (pneumonia by X-ray, positive blood or urine culture) or multi-organ failure
Other or concomitant liver disease present: viral hepatitis, autoimmune liver disease, metabolic liver disease, vascular liver disease
Cow milk allergy or severe lactose intolerance
Active GI bleeding
Untreated spontaneous bacterial peritonitis based on >250 polymorphonuclear cells or positive culture
Acute kidney injury at time of randomization with Creatinine > 1.5 md/dL
Evidence of acute pancreatitis (by imaging and lipase) or biliary obstruction (dilated bile ducts)
Subjects who are pregnant or lactating
Significant systemic or major illness, that, in the opinion of the Investigator would preclude the patient from participating in and completing the study
Patients requiring the use of vasopressors or inotropic support in 12 hours prior to randomization
Treatment for alcoholic hepatitis within 1 month of study entry with corticosteroids use>1 week immediately prior to the time of entry into the study.
Any patient who has received any investigational drug or device within 30 days of dosing or who is scheduled to receive another investigational drug or device in the course of the study.

Arm && Interventions

Group	Intervention	Description
IMM 124-E 2400 mg/day	IMM 124-E (Hyperimmune Bovine Colostrum)	Imm-124-E (2400 mg/day) will be provided in two divided doses daily in the form of powder to be mixed with water. Subjects will get 1 active drug powder and 1 placebo powder with each dosing for a total of 4 sachets daily.
IMM 124-E 2400 mg/day	Placebo (High protein milk powder)	Imm-124-E (2400 mg/day) will be provided in two divided doses daily in the form of powder to be mixed with water. Subjects will get 1 active drug powder and 1 placebo powder with each dosing for a total of 4 sachets daily.
IMM 124-E 4800 mg/day	IMM 124-E (Hyperimmune Bovine Colostrum)	Imm-124-E (4800 mg/day) will be provided in two divided doses daily in the form of 2400 mg in the form of a powder to be mixed with water. The total number daily will be 4 sachets.
Placebo (High protein milk powder)	Placebo (High protein milk powder)	Subjects will receive 2 sachets of placebo powder to be mixed with water in the morning and 2 sachets of placebo powder (to be mixed with water) in the evening for a total of 4 sachets of placebo daily.

Primary Outcome Measures

Name	Time	Method
Other Safety Endpoints	30 Days	Number of incidents of all other serious adverse events and other adverse events not already assessed as a primary outcome.
Gastrointestinal Safety Endpoints	30 Days	Number of events and severity of gastrointestinal events, including nausea, vomiting, and diarrhea
Combined Kidney, Brain, and Lung Safety Endpoints	30 Days	Number of incidents of the following: renal failure, encephalopathy or pulmonary compromise.
Infection Safety Endpoints	30 Days	Number of incidents of sepsis.

Secondary Outcome Measures

Name	Time	Method
Mortality	180 days	Number of deaths due to any cause
Bowel Gastrointestinal Safety Endpoints	30 Days	Number of participants who experience diarrhea
Change in Circulating Endotoxin Levels	Baseline, day 28	Changes in endotoxin levels as measured using a standard blood assay
SOFA Score	30 days	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.
Lille Model Score	7 days	Number of participants who meet Lille criteria indicating failure to respond to treatment
Change in Liver Function	90 days	Model for end-stage liver disease (MELD) score ranges from 6 to 40 with higher number indicating worse liver function.
Change in Serum Bile Acids	Baseline to 90 days	Serum bile acids levels as measured using standard blood serum assay
Time to 50% Drop in Bilirubin	180 days	Length of time to a drop in bilirubin of 50% measured in days
Cytokine Data	28 days	Changes in cytokine profile across study arms at day 28

Locations (3): Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
Indiana University
🇺🇸
Indianapolis, Indiana, United States
Virginia Commonwealth University
🇺🇸
Richmond, Virginia, United States