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

Virginia Commonwealth University (VCU)

Status and phase: Completed; Phase 2

Conditions: Hepatitis, Alcoholic

Treatments: Drug: IMM 124-E (Hyperimmune Bovine Colostrum); Drug: Placebo (High protein milk powder)

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT01968382

U01AA021891 (U.S. NIH Grant/Contract)

HM20000157

IMM-124-E (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 57 patients

Sex: All

Ages: 21+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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57 participants in 3 patient groups, including a placebo group

IMM 124-E 2400 mg/day

Experimental group

Description:

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.

Treatment:

Drug: IMM 124-E (Hyperimmune Bovine Colostrum)

Drug: Placebo (High protein milk powder)

IMM 124-E 4800 mg/day

Experimental group

Description:

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.

Treatment:

Drug: IMM 124-E (Hyperimmune Bovine Colostrum)

Placebo (High protein milk powder)

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo (High protein milk powder)