Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date  ICMJE August 30, 2013
First Posted Date  ICMJE October 24, 2013
Results First Submitted Date  ICMJE December 13, 2019
Results First Posted Date  ICMJE January 27, 2020
Last Update Posted Date January 27, 2020
Study Start Date  ICMJE December 2014
Actual Primary Completion Date December 22, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 24, 2020)
  • Gastrointestinal Safety Endpoints [ Time Frame: 30 Days ]
    Number of events and severity of gastrointestinal events, including nausea, vomiting, and diarrhea
  • Combined Kidney, Brain, and Lung Safety Endpoints [ Time Frame: 30 Days ]
    Number of incidents of the following: renal failure, encephalopathy or pulmonary compromise.
  • Infection Safety Endpoints [ Time Frame: 30 Days ]
    Number of incidents of sepsis.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 18, 2013)
Greater decrease in mean circulating endotoxin levels in those receiving Steroids+ Imm 124-E compared to steroids + placebo [ Time Frame: 7 months ]
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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 24, 2020)
  • Bowel Gastrointestinal Safety Endpoints [ Time Frame: 30 Days ]
    Number of participants who experience diarrhea
  • Change in Circulating Endotoxin Levels [ Time Frame: Baseline, day 28 ]
    Changes in endotoxin levels as measured using a standard blood assay
  • Lille Model Score [ Time Frame: 7 days ]
    Number of participants who meet Lille criteria indicating failure to respond to treatment
  • Mortality [ Time Frame: 180 days ]
    Number of deaths due to any cause
  • 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.
  • 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.
  • Change in Serum Bile Acids [ Time Frame: Baseline to 90 days ]
    Serum bile acids levels as measured using standard blood serum assay
  • Time to 50% Drop in Bilirubin [ Time Frame: 180 days ]
    Length of time to a drop in bilirubin of 50% measured in days
  • Cytokine Data [ Time Frame: 28 days ]
    Changes in cytokine profile across study arms at day 28
Original Secondary Outcome Measures  ICMJE
 (submitted: October 18, 2013)
  • Microbiome-metagenomic-immunologic data [ Time Frame: 28 Days ]
    Changes in microbiome composition of stool across study arms at day 28
  • Efficacy related outcomes [ Time Frame: 180 days ]
    1. # 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 ]
    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 ]
    Changes in microbial metabolome in blood across study arms at day 28
  • Microbiome-metagenomic-immunologic data [ Time Frame: 28 days ]
    Changes in cytokine profile across study arms at day 28
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of IMM 124-E for Patients With Severe Alcoholic Hepatitis
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Hepatitis, Alcoholic
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: IMM 124-E (Hyperimmune Bovine Colostrum)
    • Drug: Placebo (High protein milk powder)
  • 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.
    Intervention: Drug: IMM 124-E (Hyperimmune Bovine Colostrum)
  • 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.
    Intervention: Drug: Placebo (High protein milk powder)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 24, 2020)
57
Original Estimated Enrollment  ICMJE
 (submitted: October 18, 2013)
66
Actual Study Completion Date  ICMJE December 22, 2018
Actual Primary Completion Date December 22, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01968382
Other Study ID Numbers  ICMJE HM20000157
U01AA021891 ( U.S. NIH Grant/Contract )
IMM-124-E ( Other Identifier: VCU )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Virginia Commonwealth University
Study Sponsor  ICMJE Virginia Commonwealth University
Collaborators  ICMJE
  • National Institute on Alcohol Abuse and Alcoholism (NIAAA)
  • Immuron Ltd.
Investigators  ICMJE
Principal Investigator: Arun J Sanyal, MBBS MD Virginia Commonwealth University
PRS Account Virginia Commonwealth University
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP