search
Back to results

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

Primary Purpose

Hepatitis, Alcoholic

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
IMM 124-E (Hyperimmune Bovine Colostrum)
Placebo (High protein milk powder)
Sponsored by
Virginia Commonwealth University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis, Alcoholic focused on measuring IMM 124-E, Bovine Colostrum, Alcoholic, Hepatitis, LPS, Hyper-immune

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Indiana University
  • Mayo Clinic
  • Virginia Commonwealth University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

IMM 124-E 2400 mg/day

IMM 124-E 4800 mg/day

Placebo (High protein milk powder)

Arm Description

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) 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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
August 30, 2013
Last Updated
January 24, 2020
Sponsor
Virginia Commonwealth University
Collaborators
National Institute on Alcohol Abuse and Alcoholism (NIAAA), Immuron Ltd.
search

1. Study Identification

Unique Protocol Identification Number
NCT01968382
Brief Title
Safety and Efficacy of IMM 124-E for Patients With Severe Alcoholic Hepatitis
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
December 2014 (undefined)
Primary Completion Date
December 22, 2018 (Actual)
Study Completion Date
December 22, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Virginia Commonwealth University
Collaborators
National Institute on Alcohol Abuse and Alcoholism (NIAAA), Immuron Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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: Mechanistic endpoints: TNF-α, immune-inflammatory markers, microbiome-metagenome 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 Safety related: tolerability, adverse events.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis, Alcoholic
Keywords
IMM 124-E, Bovine Colostrum, Alcoholic, Hepatitis, LPS, Hyper-immune

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
57 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IMM 124-E 2400 mg/day
Arm Type
Experimental
Arm Description
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.
Arm Title
IMM 124-E 4800 mg/day
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo (High protein milk powder)
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
IMM 124-E (Hyperimmune Bovine Colostrum)
Intervention Description
Hyper-immune bovine colostrum enriched with anti-LPS antibodies and which has been designated by Immuron as IMM-124E.
Intervention Type
Drug
Intervention Name(s)
Placebo (High protein milk powder)
Intervention Description
Subjects will receive a total of 4 sachets (2 in the morning and 2 in the evening) daily
Primary Outcome Measure Information:
Title
Gastrointestinal Safety Endpoints
Description
Number of events and severity of gastrointestinal events, including nausea, vomiting, and diarrhea
Time Frame
30 Days
Title
Combined Kidney, Brain, and Lung Safety Endpoints
Description
Number of incidents of the following: renal failure, encephalopathy or pulmonary compromise.
Time Frame
30 Days
Title
Infection Safety Endpoints
Description
Number of incidents of sepsis.
Time Frame
30 Days
Title
Other Safety Endpoints
Description
Number of incidents of all other serious adverse events and other adverse events not already assessed as a primary outcome.
Time Frame
30 Days
Secondary Outcome Measure Information:
Title
Bowel Gastrointestinal Safety Endpoints
Description
Number of participants who experience diarrhea
Time Frame
30 Days
Title
Change in Circulating Endotoxin Levels
Description
Changes in endotoxin levels as measured using a standard blood assay
Time Frame
Baseline, day 28
Title
Lille Model Score
Description
Number of participants who meet Lille criteria indicating failure to respond to treatment
Time Frame
7 days
Title
Mortality
Description
Number of deaths due to any cause
Time Frame
180 days
Title
Change in Liver Function
Description
Model for end-stage liver disease (MELD) score ranges from 6 to 40 with higher number indicating worse liver function.
Time Frame
90 days
Title
SOFA Score
Description
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
Title
Change in Serum Bile Acids
Description
Serum bile acids levels as measured using standard blood serum assay
Time Frame
Baseline to 90 days
Title
Time to 50% Drop in Bilirubin
Description
Length of time to a drop in bilirubin of 50% measured in days
Time Frame
180 days
Title
Cytokine Data
Description
Changes in cytokine profile across study arms at day 28
Time Frame
28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Arun J Sanyal, MBBS MD
Organizational Affiliation
Virginia Commonwealth University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs