Clinical trial NCT01968382: Safety and Efficacy of IMM 124-E for Patients With Severe Alcoholic Hepatitis
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis, Alcoholic
Keywords: IMM 124-E
Bovine Colostrum
Alcoholic
Hepatitis
LPS
Hyper-immune
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
name: Immuron Ltd.
First posted: 2013-10-24
Enrollment: 57
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Gastrointestinal Safety Endpoints
timeFrame: 30 Days
measure: Combined Kidney, Brain, and Lung Safety Endpoints
timeFrame: 30 Days
measure: Infection Safety Endpoints
timeFrame: 30 Days
measure: Other Safety Endpoints
timeFrame: 30 Days
Secondary outcomes:
measure: Bowel Gastrointestinal Safety Endpoints
timeFrame: 30 Days
measure: Change in Circulating Endotoxin Levels
timeFrame: Baseline, day 28
measure: Lille Model Score
timeFrame: 7 days
measure: Mortality
timeFrame: 180 days
measure: Change in Liver Function
timeFrame: 90 days
measure: SOFA Score
timeFrame: 30 days
measure: Change in Serum Bile Acids
timeFrame: Baseline to 90 days
measure: Time to 50% Drop in Bilirubin
timeFrame: 180 days
measure: Cytokine Data
timeFrame: 28 days
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Virginia Commonwealth University
name: Arun J Sanyal, MBBS MD
role: PRINCIPAL_INVESTIGATOR
References: