Status:
COMPLETED
IL-1 Signal Inhibition in Alcoholic Hepatitis
Lead Sponsor:
Imperial College London
Collaborating Sponsors:
Novartis Pharmaceuticals
Conditions:
Alcoholic Hepatitis
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief 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 fatalit...
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 multicent...
Eligibility Criteria
Inclusion
- Male and female patients aged 18 years or older at screening
- Clinical diagnosis of alcoholic hepatitis at screening:
- Serum bilirubin \> 80μmol/L
- History of excess alcohol (\> 80g/day male, \> 60g/day female) to within 6 weeks before screening visit
- Less than 4 weeks since admission to hospital at baseline visit
- mDF\* ≥ 32 and MELD ≤ 27 at baseline visit
- Informed consent
- Women of child-bearing potential have to use an effective contraception method (as specified in section 9.6).
Exclusion
- Alcohol abstinence of \>6 weeks prior to randomization/baseline visit
- Duration of clinically apparent jaundice \> 3 months before baseline visit
- Other causes of liver disease including:
- Evidence of chronic viral hepatitis (Hepatitis B or C)
- Biliary obstruction
- Hepatocellular carcinoma
- Evidence of current malignancy (except non-melanotic skin cancer)
- Previous entry into the study, or use of either prednisolone or any systemic steroids (equivalent to a dose of systemic prednisolone \>20mg) within 6 weeks of screening.
- AST \>500 U/L or ALT \>300 U/L (not compatible with alcoholic hepatitis)
- Patients with a serum creatinine \>220 μmol/L (2.5 mg / dL) or requiring renal support (see below)
- Patients dependent upon inotropic support (adrenaline or noradrenaline). Terlipressin is allowed
- Variceal haemorrhage on this admission
- Untreated sepsis (see below)
- Patients with known hypersensitivity or contraindications to Canakinumab
- Patients with cerebral haemorrhage, extensive retinal haemorrhage, acute myocardial infarction (within the last 6 weeks) or severe cardiac arrhythmias (not including atrial fibrillation)
- Pregnant or lactating women
- Patients treated with other IL-1 inhibitors and biologics or any other immunosuppressants within 3 months of study participation.
- Known infection with HIV at screening or randomization
- History or evidence of tuberculosis (TB) (active or latent) infection
- Active ongoing inflammatory diseases other than AAH that might confound the evaluation of the benefit of canakinumab therapy
- Underlying metabolic, hematologic, renal, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal conditions, including neutropenia (ANC \<1.5) and leukopenia, which in the opinion of the investigator immune-compromises the subject and/or places the subject at unacceptable risk for participation in an immunomodulatory therapy.
- Significant medical problems or diseases, including but not limited to the following: uncontrolled hypertension (≥160/95 mmHg), congestive heart failure \[New York Heart Association status of class III or IV\], uncontrolled diabetes
- Vaccination with a live vaccine within 3 month before baseline
Key Trial Info
Start Date :
February 12 2019
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
March 31 2023
Estimated Enrollment :
55 Patients enrolled
Trial Details
Trial ID
NCT03775109
Start Date
February 12 2019
End Date
March 31 2023
Last Update
March 11 2025
Active Locations (16)
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1
University Hospitals Bristol NHS Foundation Trust
Bristol, United Kingdom
2
Glasgow Royal Infirmary, Greater Glasgow & Clyde
Glasgow, United Kingdom, G4 0SF
3
Queen Elizabeth University Hospital
Glasgow, United Kingdom
4
Leeds Teaching Hospitals NHS Trust
Leeds, United Kingdom