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

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ClinicalTrials.gov Identifier: NCT01968382
Recruitment Status : Completed
First Posted : October 24, 2013
Results First Posted : January 27, 2020
Last Update Posted : January 27, 2020
Sponsor:
Collaborators:
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Immuron Ltd.
Information provided by (Responsible Party):
Virginia Commonwealth University

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.


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

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 57 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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
Study Start Date : December 2014
Actual Primary Completion Date : December 22, 2018
Actual Study Completion Date : December 22, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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 sachets 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 sachets (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 sachets.
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 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.
Drug: Placebo (High protein milk powder)
Subjects will receive a total of 4 sachets (2 in the morning and 2 in the evening) daily




Primary Outcome Measures :
  1. Gastrointestinal Safety Endpoints [ Time Frame: 30 Days ]
    Number of events and severity of gastrointestinal events, including nausea, vomiting, and diarrhea

  2. Combined Kidney, Brain, and Lung Safety Endpoints [ Time Frame: 30 Days ]
    Number of incidents of the following: renal failure, encephalopathy or pulmonary compromise.

  3. Infection Safety Endpoints [ Time Frame: 30 Days ]
    Number of incidents of sepsis.

  4. Other Safety Endpoints [ Time Frame: 30 Days ]
    Number of incidents of all other serious adverse events and other adverse events not already assessed as a primary outcome.


Secondary Outcome Measures :
  1. Bowel Gastrointestinal Safety Endpoints [ Time Frame: 30 Days ]
    Number of participants who experience diarrhea

  2. Change in Circulating Endotoxin Levels [ Time Frame: Baseline, day 28 ]
    Changes in endotoxin levels as measured using a standard blood assay

  3. Lille Model Score [ Time Frame: 7 days ]
    Number of participants who meet Lille criteria indicating failure to respond to treatment

  4. Mortality [ Time Frame: 180 days ]
    Number of deaths due to any cause

  5. Change in Liver Function [ Time Frame: 90 days ]
    Model for end-stage liver disease (MELD) score ranges from 6 to 40 with higher number indicating worse liver function.

  6. SOFA Score [ Time Frame: 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.

  7. Change in Serum Bile Acids [ Time Frame: Baseline to 90 days ]
    Serum bile acids levels as measured using standard blood serum assay

  8. Time to 50% Drop in Bilirubin [ Time Frame: 180 days ]
    Length of time to a drop in bilirubin of 50% measured in days

  9. Cytokine Data [ Time Frame: 28 days ]
    Changes in cytokine profile across study arms at day 28



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01968382


Locations
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United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Virginia Commonwealth University
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Immuron Ltd.
Investigators
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Principal Investigator: Arun J Sanyal, MBBS MD Virginia Commonwealth University
  Study Documents (Full-Text)

Documents provided by Virginia Commonwealth University:
Informed Consent Form  [PDF] August 10, 2017

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Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT01968382    
Other Study ID Numbers: HM20000157
U01AA021891 ( U.S. NIH Grant/Contract )
IMM-124-E ( Other Identifier: VCU )
First Posted: October 24, 2013    Key Record Dates
Results First Posted: January 27, 2020
Last Update Posted: January 27, 2020
Last Verified: January 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Virginia Commonwealth University:
IMM 124-E
Bovine Colostrum
Alcoholic
Hepatitis
LPS
Hyper-immune
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis
Hepatitis, Alcoholic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Liver Diseases, Alcoholic
Alcohol-Induced Disorders
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders