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

NCT01968382 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: HM20000157U01AA021891IMM-124-E
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 3

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.

Conditions

Hepatitis, Alcoholic

Keywords

IMM 124-E; Bovine Colostrum; Alcoholic; Hepatitis; LPS; Hyper-immune

Outcome Measures

Primary Outcomes (4)

• Gastrointestinal Safety Endpoints

  Number of events and severity of gastrointestinal events, including nausea, vomiting, and diarrhea

  30 Days

• Combined Kidney, Brain, and Lung Safety Endpoints

  Number of incidents of the following: renal failure, encephalopathy or pulmonary compromise.

  30 Days

• Infection Safety Endpoints

  Number of incidents of sepsis.

  30 Days

• Other Safety Endpoints

  Number of incidents of all other serious adverse events and other adverse events not already assessed as a primary outcome.

  30 Days

Secondary Outcomes (9)

• Bowel Gastrointestinal Safety Endpoints

  30 Days

• Change in Circulating Endotoxin Levels

  Baseline, day 28

• Lille Model Score

  7 days

• Mortality

  180 days

• Change in Liver Function

  90 days

Study Arms (3)

IMM 124-E 2400 mg/day

EXPERIMENTAL

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); Drug: Placebo (High protein milk powder)

IMM 124-E 4800 mg/day

EXPERIMENTAL

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)

Placebo (High protein milk powder)

PLACEBO COMPARATOR

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)

Interventions

IMM 124-E (Hyperimmune Bovine Colostrum) DRUG

Hyper-immune bovine colostrum enriched with anti-LPS antibodies and which has been designated by Immuron as IMM-124E.

IMM 124-E 2400 mg/day; IMM 124-E 4800 mg/day

Placebo (High protein milk powder) DRUG

Subjects will receive a total of 4 sachets (2 in the morning and 2 in the evening) daily

IMM 124-E 2400 mg/day; Placebo (High protein milk powder)

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator
• Immuron Ltd.: collaborator

Study Sites (3)

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Conditions

Hepatitis, Alcoholic; Hepatitis

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders

Results Point of Contact

• Title: Stephanie Taylor MSN, RN
• Organization: Virginia Commonwealth University

stephanie.taylor@vcuhealth.org

804-828-9311

Study Officials

• Arun J Sanyal, MBBS MD

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2013
• First Posted: October 24, 2013
• Study Start: December 1, 2014
• Primary Completion: December 22, 2018
• Study Completion: December 22, 2018
• Last Updated: January 27, 2020
• Results First Posted: January 27, 2020

Record last verified: 2020-01

Locations

US (3)