Alcoholic Hepatitis MedDRA version: 20.0 Level: LLT Classification code 10001624 Term: Alcoholic hepatitis System Organ Class: 100000004871
Conditions
Interventions
Trade Name: Ilaris
Product Name: Ilaris
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: Canakinumab
CAS Number
Sponsors
Imperial College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: * 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 defined in detail in study protocol) Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 52 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: • 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: o Evidence of chronic viral hepatitis (Hepatitis B or C) o Biliary obstruction o Hepatocellular carcinoma • Evidence of current malignancy (except non-melanotic skin cancer) • Previous entry into the study, or use of either prednisolone 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 • Patients dependent upon inotropic support (adrenaline or noradrenaline). Terlipressin is allowed • Variceal haemorrhage on this admission • Untreated sepsis • 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 • 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective is to explore the potential benefits of the IL-1ß antibody, Canakinumab, in the treatment of alcoholic hepatitis; Secondary Objective: We wish to determine whether Canakinumab reduces mortality rates in patients with severe alcoholic hepatitis at 90 days, increases the rate of recovery of liver function, reduces the risk of acute kidney injury and reduces the risk of the systemic inflammatory response syndrome (SIRS). We wish to determine the safety and tolerability of Canakinumab and establish whether Canakinumab influences the risk of infection. We will evaluate whether identification of patients with a high infection risk using bacterial DNA measurement coupled with antibiotic prophylaxis is a successful strategy. ;Primary end point(s): Histological improvement of alcoholic hepatitis on liver biopsy after 28 days of treatment compared to baseline ;Timepoint(s) of evaluation of this end point: 28 days after baseline / randomisation into the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Improvement of individual components (polymorphonuclear cell infiltrate, ballooned hepatocytes and steatosis) of alcoholic hepatitis on liver histology from baseline to Day 28 • Changes in the components of Alcoholic Hepatitis Histological Score (AHHS) (1) from baseline to Day 28 • Changes in the components of Nonalcoholic fatty liver disease activity score (NAS) score from baseline to Day 28 • Changes in hepatic venous pressure gradient (HVPG) between baseline and day 28 • Changes of serum CK18-M30/M65 from baseline to Day 7, 14, 21, 28, 42 and 90 • Change in serum bilirubin from baseline to Day 7, 14, 28, 21, 42 and 90 • Change in MELD score at from baseline to Day 7, 14, 21, 28, 42 and 90 • Change in Glasgow alcoholic hepatitis score (GAHS) from baseline to Day 7, 14, 21, 28, 42 and 90 • Change in mDF score from baseline to Day 7, 14, 21, 28, 42 and 90 • Lille score at Day 7 • Resolution of systemic inflammatory response syndrome (SIRS) at Day 7, 14, 21, 28, 42 and 90 in patients with SIRS at baseline • Incidence of SIRS at Day 7, 14, 21, 28, 42 and 90 in patients without SIRS at baseline • Mortality rate at Day 90 • Incidence of infection and sepsis over 90 days • Incidence of acute kidney injury over 90 days • Incidence of variceal haemorrhage, ascites or encephalopathy over 90 days • safety and tolerability of canakinumab • Serum and plasma biomarkers of hepatic function and inflammation including cytokine profiles which may indicate the degree of response to IL-1b inhibition. • Changes in CRP over time • Length of hospital stay ;Timepoint(s) of evaluation of this end point: As detailed in the above box | — |
Countries
United Kingdom
Contacts
Public ContactProfessor Mark Thursz
Imperial College
Outcome results
None listed