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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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 Hepat

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 Summary:

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.

Sponsor: Virginia Commonwealth University

Current Primary Outcome: 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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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. 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 ]
    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


Original Secondary Outcome:

  • 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


Information By: Virginia Commonwealth University

Dates:
Date Received: August 30, 2013
Date Started: December 2014
Date Completion: January 2018
Last Updated: February 22, 2017
Last Verified: February 2017