NCT03775109

IL-1 Signal Inhibition in Alcoholic Hepatitis

IL-1 Signal Inhibition in Alcoholic Hepatitis (ISAIAH)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 55 (actual)
• Sponsor: Imperial College London · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Alcoholic hepatitis (AH) is a florid presentation of alcoholic liver disease characterized by liver failure in the context of recent and heavy alcohol consumption. The condition carries a high fatality risk; patients with severe AH have a 30% mortality rate at 90 days after presentation. Currently there is no effective treatment for severe alcoholic hepatitis. Based on the current understanding of the disease pathogenesis IL-1 (interleukin) is a key mediator of hepatic inflammation responsible for metabolic disturbances, fibrogenesis stellate cell activation and consequently portal hypertension. Canakinumab is a licensed monoclonal antibody inhibitor of IL-1 and may consequently reverse the adverse effects of the cytokine in patients with this disorder. Therefore, the main objective of the ISAIAH trial is to explore the potential benefits of the IL-1β antibody, Canakinumab (solution for injection), in the treatment of alcoholic hepatitis. ISAIAH is a multicentre, double blind, randomized (1:1), placebo controlled trial. The trial will follow patients up for 90 days and will be conducted in centres across the United Kingdom. Twenty-six patients will be recruited to each arm of the trial: total 52 patients.

Detailed description

The main objective of the ISAIAH trial is to explore the potential benefits of the IL-1β antibody, Canakinumab (solution for injection), in the treatment of alcoholic hepatitis. ISAIAH is a multicentre, double blind, randomized (1:1), placebo controlled trial. The trial will follow patients up for 90 days and will be conducted in centres across the United Kingdom. Twenty-six patients will be recruited to each arm of the trial: total 52 patients. The trial will be conducted in patients with severe alcoholic hepatitis (mDF\* ≥ 32 and MELD ≤27) with treatment initiated during an index hospital admission with the condition. The primary endpoint of the trial is histological improvement of alcoholic hepatitis on liver biopsy after 28 days of treatment compared to baseline. Histological improvement is defined as a reduction in lobular inflammation (regardless of cell type). Patients meeting the eligibility criteria will be randomized and treated. A single dose of 3 mg/kg Canakinumab or identical placebo will be administered intravenously at baseline (Day 1). Canakinumab will be made up by dilution in 100 ml 5% Dextrose by an unblinded research personnel at each site. Patients with AST \>2 x ULN on Day 28 will receive a second dose of 3 mg/kg study drug administered i.v. on Day 28. Patients who received placebo on baseline will receive placebo. Patients who received canakinumab on baseline will receive canakinumab. Total follow up time for each patient is 90 days.

Conditions

• Alcoholic Hepatitis

Interventions

Type	Name	Description
DRUG	Canakinumab 150mg/ml solution for injection	Canakinumab 150mg/ml solution for injection
DRUG	Placebo	100ml 5% Dextrose

Timeline

• Start date: 2019-02-12
• Primary completion: 2023-03-31
• Completion: 2023-03-31
• First posted: 2018-12-13
• Last updated: 2025-03-11
• Results posted: 2025-03-11

Locations

16 sites across 1 country: United Kingdom