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

Hepatitis, Alcoholic Clinical Trial

— TREAT  

Official title:

A Multicenter Randomized, Double-Blind, Placebo-controlled, Dosing, Safety and Efficacy Study of IMM 124-E (Hyperimmune Bovine Colostrum) for Patients With Severe Alcoholic Hepatitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01968382
• Other study ID #: HM20000157
• Secondary ID: U01AA021891IMM-1
• Status: Completed
• Phase: Phase 2
• Start date: December 2014
• Est. completion date: December 22, 2018

Study information

• Verified date: January 2020
• Source: Virginia Commonwealth University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: December 22, 2018
• Est. primary completion date: December 22, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

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.

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis, Alcoholic

Intervention

Drug:
• IMM 124-E (Hyperimmune Bovine Colostrum)
Hyper-immune bovine colostrum enriched with anti-LPS antibodies and which has been designated by Immuron as IMM-124E.
• Placebo (High protein milk powder)
Subjects will receive a total of 4 sachets (2 in the morning and 2 in the evening) daily

Locations

Country	Name	City	State
United States	Indiana University	Indianapolis	Indiana
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (3)

Lead Sponsor	Collaborator
Virginia Commonwealth University	Immuron Ltd., National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Gastrointestinal Safety Endpoints	Number of events and severity of gastrointestinal events, including nausea, vomiting, and diarrhea	30 Days
Primary	Combined Kidney, Brain, and Lung Safety Endpoints	Number of incidents of the following: renal failure, encephalopathy or pulmonary compromise.	30 Days
Primary	Infection Safety Endpoints	Number of incidents of sepsis.	30 Days
Primary	Other Safety Endpoints	Number of incidents of all other serious adverse events and other adverse events not already assessed as a primary outcome.	30 Days
Secondary	Bowel Gastrointestinal Safety Endpoints	Number of participants who experience diarrhea	30 Days
Secondary	Change in Circulating Endotoxin Levels	Changes in endotoxin levels as measured using a standard blood assay	Baseline, day 28
Secondary	Lille Model Score	Number of participants who meet Lille criteria indicating failure to respond to treatment	7 days
Secondary	Mortality	Number of deaths due to any cause	180 days
Secondary	Change in Liver Function	Model for end-stage liver disease (MELD) score ranges from 6 to 40 with higher number indicating worse liver function.	90 days
Secondary	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.	30 days
Secondary	Change in Serum Bile Acids	Serum bile acids levels as measured using standard blood serum assay	Baseline to 90 days
Secondary	Time to 50% Drop in Bilirubin	Length of time to a drop in bilirubin of 50% measured in days	180 days
Secondary	Cytokine Data	Changes in cytokine profile across study arms at day 28	28 days