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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2015 by Virginia Commonwealth University
Sponsor:
Collaborators:
Immuron Ltd.
Information provided by (Responsible Party):
Virginia Commonwealth University
ClinicalTrials.gov Identifier:
NCT01968382
First received: August 30, 2013
Last updated: April 20, 2015
Last verified: April 2015
  Purpose

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).

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.


Condition Intervention Phase
Hepatitis, Alcoholic
Drug: IMM 124-E (Hyperimmune Bovine Colostrum)
Drug: Placebo (High protein milk powder)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Virginia Commonwealth University:

Primary Outcome Measures:
  • Greater decrease in mean circulating endotoxin levels in those receiving Steroids+ Imm 124-E compared to steroids + placebo [ Time Frame: 7 months ] [ Designated as safety issue: No ]
    Means for continuous variables at end of study will be analyzed adjusting for baseline values using ANCOVA. We expect to show a greater decrease in mean circulating endotoxin levels in those receiving Steroids+ Imm 124-E compared to steroids + placebo.


Secondary Outcome Measures:
  • Microbiome-metagenomic-immunologic data [ Time Frame: 28 Days ] [ Designated as safety issue: No ]
    Changes in microbiome composition of stool across study arms at day 28

  • Efficacy related outcomes [ Time Frame: 180 days ] [ Designated as safety issue: No ]
    1. Number of subjects who meet Lille criteria at day 7
    2. Mortality at days 30, 90 and 180
    3. Change in MELD scores from baseline to day 7, 30, 90
    4. Sequential organ failure assessment score at day 7, 30
    5. Changes in serum bile acids from baseline to day 7, 30 and 90
    6. Time to drop in bilirubin by 50%

  • Safety Related endpoints [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
    1. Incidence and severity of gastrointestinal events, including nausea, vomiting, and diarrhea
    2. Proportion of subjects who develop renal failure, encephalopathy or pulmonary compromise
    3. Frequency of sepsis
    4. Frequency of other adverse events

  • Microbiome-metagenomic-immunologic data [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Changes in microbial metabolome in blood across study arms at day 28

  • Microbiome-metagenomic-immunologic data [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Changes in cytokine profile across study arms at day 28


Estimated Enrollment: 66
Study Start Date: December 2014
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IMM 124-E 2400 mg/day
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 bottles daily.
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.
Drug: Placebo (High protein milk powder)
Subjects will receive a total of 4 bottles (2 in the morning and 2 in the evening) daily
Experimental: IMM 124-E 4800 mg/day
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 bottles.
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 Comparator: Placebo (High protein milk powder)
Subjects will receive 2 bottles of placebo powder to be mixed with water in the morning and 2 bottles of placebo powder (to be mixed with water) in the evening for a total of 4 bottles of placebo daily.
Drug: Placebo (High protein milk powder)
Subjects will receive a total of 4 bottles (2 in the morning and 2 in the evening) daily

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.
  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01968382

Contacts
Contact: Susan A Walker, RN, MSN 804-628-4395 walkersa@vcu.edu

Locations
United States, Indiana
Indiana University Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Angela Howell, RN    317-278-9296    anmhowel@iu.edu   
Principal Investigator: Naga Chalasani, MD         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Sarah Wilder, RN, BSN    507-284-2698    wilder.sarah@mayo.edu   
Principal Investigator: Vijay Shah, MD         
United States, Virginia
Virginia Commonwealth University Recruiting
Richmond, Virginia, United States, 23298
Contact: Susan A Walker, RN, MSN    804-628-4395    walkersa@vcu.edu   
Principal Investigator: Arun J Sanyal, MBBS MD         
Sub-Investigator: Puneet Puri, MBBS MD         
Sponsors and Collaborators
Virginia Commonwealth University
Immuron Ltd.
Investigators
Principal Investigator: Arun J Sanyal, MBBS MD Virginia Commonwealth University
  More Information

No publications provided

Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT01968382     History of Changes
Other Study ID Numbers: IMM 124-E, U01AA021891
Study First Received: August 30, 2013
Last Updated: April 20, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Virginia Commonwealth University:
IMM 124-E
Bovine Colostrum
Alcoholic
Hepatitis
LPS
Hyper-immune

Additional relevant MeSH terms:
Hepatitis, Alcoholic
Hepatitis
Hepatitis A
Alcohol-Induced Disorders
Alcohol-Related Disorders
Chemically-Induced Disorders
Digestive System Diseases
Enterovirus Infections
Hepatitis, Viral, Human
Liver Diseases
Liver Diseases, Alcoholic
Picornaviridae Infections
RNA Virus Infections
Substance-Related Disorders
Virus Diseases

ClinicalTrials.gov processed this record on July 27, 2015