Alcoholic HepatitisPhase 2ISAIAHNCT03775109
IL-1 Signal Inhibition in Alcoholic Hepatitis
A Phase 2 study testing Canakinumab 150mg/ml solution for injection in people with Alcoholic Hepatitis, run by Imperial College London at 16 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Alcoholic Hepatitis
- What is being tested?
- Canakinumab 150mg/ml solution for injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 55 participants
- Where
- 16 sitesUnited Kingdom
- Study dates
- 12 Feb 2019to 31 Mar 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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
Show all 23Show fewer
- 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
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
United Kingdom16 sites
University Hospitals Bristol NHS Foundation Trust
Bristol
Glasgow Royal Infirmary, Greater Glasgow & Clyde
Glasgow, G4 0SF
Queen Elizabeth University Hospital
Glasgow
Leeds Teaching Hospitals NHS Trust
Leeds
Aintree University Hospital
Liverpool
Royal Liverpool and Broadgreen University Hospitals NHS Trust
Liverpool
Imperial College Healthcare NHS Foundation Trust
London, W2 1NY
Chelsea and Westminster Hospital NHS Foundation Trust
London
King's College Hospital NHS Foundation Trust
London
Royal Free London NHS Foundation Trust
London
St George's University Hospitals NHS Foundation Trust
London
The Newcastle Upon Tyne Hospitals NHS Foundation Trust
Newcastle upon Tyne
Nottingham University Hospitals NHS Trust
Nottingham
John Radcliffe Hospital, Oxford University NHS Foundation Trust
Oxford, OX3 9DU
Plymouth Hospitals NHS Trust
Plymouth
University Hospital Southampton NHS Foundation Trust
Southampton
About this study
Official title: IL-1 Signal Inhibition in Alcoholic Hepatitis (ISAIAH)
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.
Read more
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.
Read the 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
- Being tested
- Canakinumab 150mg/ml solution for injection, Placebo
- Keywords
- Canakinumab, Alcoholic Hepatitis, Alcohol Use Disorder, Interleukin, Treatment, Ilaris, Liver disease
- Medical subject headings
- Hepatitis, Alcoholic, Alcoholism, Liver Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Canakinumab 150mg/ml solution for injectionDrug
Canakinumab 150mg/ml solution for injection
PlaceboDrug
100ml 5% Dextrose
| Study group | Role | What they receive |
|---|---|---|
| Canakinumab 150mg/ml solution for injection | Active comparator | 150mg/ml solution for injection Receives: Drug: Canakinumab 150mg/ml solution for injection |
| Dextrose | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients Presenting 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).
Measured: Baseline and 28 days
Secondary outcomes (30)
Difference in Proportions of Participants With Improvement of Polymorphonuclear Cell Infiltrate From Baseline to Day 28.
Improvement will be recorded as a binary Yes/No outcome. The outcome will be analysed as the proportion of patients, within each treatment group, with improvement on each individual component (polymorphonuclear cell infiltrate, ballooned hepatocytes and steatosis).
Measured: Baseline and 28 days
Number of Patients Presenting Changes in Degree of Fibrosis (AHHS) From Baseline to Day 28
Where presence of bridging fibrosis or Cirrhosis at day 28 is the outcome. Firth logistic regression model was used. An intercept term and treatment indicator are the only predictor variables.
Measured: Baseline and 28 days
Number of Participants Presenting Changes in Steatosis Grade (NAS) From Baseline to Day 28
Number of patients in whom the histological degree of liver steatosis improved between baseline and day 28. Steatosis is assessed using an ordinal scale (1,2,3,4). There are four categories of steatosis grade: (1) <5%, (2) 5% to 33%, (3) >33% to 66%, and (4) >66% Ordinal logistic regression was used for statistical analysis
Measured: 28 days
Number of Participants Presenting Changes in Hepatic Venous Pressure Gradient (HVPG) Between Baseline and Day 28
This outcome measure was included in the protocol as a secondary objective. However, no data was generated as HVPG is difficult to obtain and the outcome measure was therefore abandoned
Measured: 28 days
Number of Participants Presenting Changes in Serum CK18-M30/M65 From Baseline to Day 7, 14, 21, 28, 42 and 90
Samples were not available. It was reported as a SAP deviation in the final statistical report.
Measured: Baseline and 7, 14, 21, 28, 42, 90 days
Change in Serum Bilirubin Concentration From Baseline to Day 28
Measured: 28 days
Change in MELD (Model For End-Stage Liver Disease) Score at From Baseline to Day 28
MELD score is based on the following formula: MELD Score = (9.57 * ln(Creatinine)) + (3.78 * ln(Bilirubin)) + (11.2 * ln(INR)) + 6.43. Higher score is a worse outcome. Minimum value is around 9 and maximum value is around 40.
Measured: Day 0 to day 28
Change in Glasgow Alcoholic Hepatitis Score (GAHS) From Day 28
Predicts mortality in patients with alcoholic hepatitis by laboratory results and age. GAHS score is calculated after Forrest et al., 2007 where a score of 5 to 12 is assigned based on age, WCC, Urea, PT ratio or INR and bilirubin. Higher score means a worse outcome and a score greater than or equal to 9 is associated with a poor prognosis.
Outcome measure is the score at day 28 - score at day 0
Measured: Day 0 to day 28
Change in Maddrey's Discriminant Function (mDF) Score From Baseline to Day 28
mDF is calculated using the following formula: mDF = 4.6 x (Prothrombin time - control time) + Serum Bilirubin (μmol/l) / 17. A higher score is associated with poorer prognosis. A value more than 32 implies poor outcome.
Measured: 28 days
Lille Score at Day 7
Lille score is calculated as Exp(-R)/[1+exp(-R)] where R = [3.19 - (0.101*age in years)] + (1.47*albumin at baseline in g/dL) + [0.28215* (bilirubin at baseline - bilirubin at Day 8 in mg/dL)] - [0.206 * (if creatinine>=1.3 mg/dL at baseline)] - [0.11115*bilirubin baseline in mg/dL] - (0.0096*Prothrombin Time in seconds at baseline).
The Lille Model predicts mortality rates within 6 months. Scores >0.45 predict a 6-month survival of 25%. Scores <0.45 predict a 6-month survival of 85%.
Measured: 7 days
Number of Patients With Resolution of Systemic Inflammatory Response Syndrome (SIRS) at Day 28 in Patients With SIRS at Baseline
Recommendations of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference; where SIRS represents the presence of 2 or more criteria out of following:
- Temperature < 36 ºC or > 38 ºC
- Heart rate > 90 beats/minute
- Respiratory rate > 20 breaths/minute or venous pCO2 <32 mmHg
- Leukocyte count > 12,000/mm3 or < 4,000/mm3 or band forms > 10%
Measured: 28 days
Number of Patients With Incidence of Systemic Inflammatory Response Syndrome (SIRS) at Day 28 in Patients Without SIRS at Baseline
Recommendations of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference; where SIRS represents the presence of 2 or more criteria out of following:
- Temperature < 36 ºC or > 38 ºC
- Heart rate > 90 beats/minute
- Respiratory rate > 20 breaths/minute or venous pCO2 <32 mmHg
- Leukocyte count > 12,000/mm3 or < 4,000/mm3 or band forms > 10%
Measured: 28 days
Number of Deaths at Day 90
Number of deaths per arm and hazard ratio.
Measured: 90 days
Number of Patients With Infection Over 90 Days
Measured: 90 days
Number of Patients With Acute Kidney Injury Over 90 Days
Measured: 90 days
Number of Patients With Variceal Haemorrhage Over 90 Days
Measured: 90 days
Number of Participants With Treatment-related Adverse Events
The safety and tolerability of canakinumab will be assessed through the measurement of a number of participants with treatment-related adverse events.
Measured: 90 days
Serum and Plasma Biomarkers of Hepatic Function and Inflammation Including Cytokine Profiles Which May Indicate the Degree of Response to IL-1b Inhibition.
Data were not available at time of final analysis.
The aim is to monitor baseline levels of cytokines linked to inflammasome activation and their changes after active IMP treatment. The proposed method and cytokines is as follows:
MSD 7-plex kit will be used for the detection of the following cytokines: IL-18, IL-1β*, IL-1ra, IL-6, IL-8, IFNγ** and TNF-α
ELLA 1-plex will be used for the detection of the following cytokines: IL-18Bpa
Measured: 90 days
CRP Levels at Day 28
Measured: 28 days
Length of Hospital Stay
Measured: 90 days
Difference in Proportions of Participants With Improvement of Ballooned Hepatocytes Between Treatment Groups.
Improvement will be recorded as a binary Yes/No outcome. The outcome will be analysed as the proportion of patients, within each treatment group, with 95% confidence intervals.
Measured: Day 28
Difference in Proportions of Improvement of Steatosis Between Treatment Groups at Day 28
Improvement will be recorded as a binary Yes/No outcome. The outcome will be analysed as the proportion of patients, within each treatment group, with 95% confidence intervals.
Measured: Day 28
Number of Patients Presenting Changes in Degree of Neutrophil Infiltration (AHHS) From Baseline to Day 28
Where no/mild polymorphonuclear infiltration at day 28 is the outcome. A logistic regression model was used. An intercept term, baseline measurement and treatment indicator are the only predictor variables.
Measured: day 28
Number of Patients Presenting Changes in Presence of Megamitochondria (AHHS) From Baseline to Day 28
Where no megamitochondria at day 28 is the outcome. Firth logistic regression model was used. An intercept term, baseline measurement and treatment indicator are the only predictor variables.
Measured: day 28
Number of Patients Presenting Changes in Type of Bilirubinostasis (AHHS) From Baseline to Day 28
Where there are 3 outcomes: (1) no or hepatocellular only, (2) ductular or canalicular, (3) canalicular or ductular plus hepatocellular. An ordinal logistic regression model was used. An intercept term, baseline measurement and treatment indicator are the only predictor variables.
Measured: day 28
Number of Patients Presenting Changes in Lobular Inflammation (NAS) From Baseline to Day 28
There are four categories: (1) No foci, (2) < 2 foci per 200x field, (3) 2 to 4 foci per 200x field, and (4) > 4 foci per 200x field. Ordinal logistic regression was used.
Measured: day 28
Number of Patients Presenting Changes in Hepatocyte Ballooning (NAS) From Baseline to Day 28
There are three categories: (1) none, (2) few balloon cells, and (3) many cells/prominent ballooning. Ordinal logistic regression was used.
Measured: day 28
Number of Patients With Sepsis Over 90 Days
Measured: 90 days
Number of Patients With Ascites Over 90 Days
Measured: 90 days
Number of Patients With Encephalopathy Over 90 Days
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2018
- Study start12 Feb 2019
- Primary completion31 Mar 2023
- Study completion31 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Alcoholic HepatitisStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Mark Thursz, Study director, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03775109
- Sponsor's protocol ID
- 17SM4152
- Other IDs
- 231612
- Acronym
- ISAIAH
- Status last verified
- Feb 2025
- First submitted
- 10 Dec 2018
- Last updated
- 11 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Vergis N, Patel V, Bogdanowicz K, Czyzewska-Khan J, Fiorentino F, Day E, Cross M, Foster N, Lord E, Goldin R, Forrest E, Thursz M. IL-1 Signal Inhibition In Alcoholic Hepatitis (ISAIAH): a study protocol for a multicentre, randomised, placebo-controlled trial to explore the potential benefits of canakinumab in the treatment of alcoholic hepatitis. Trials. 2021 Nov 11;22(1):792. doi: 10.1186/s13063-021-05719-2.
PubMed 34763711Vergis N, Patel V, Bogdanowicz K, Czyzewska-Khan J, Keshinro R, Fiorentino F, Day E, Middleton P, Atkinson S, Tranah T, Cross M, Babalis D, Foster N, Lord E, Quaglia A, Lloyd J, Goldin R, Rosenberg W, Parker R, Richardson P, Masson S, Whitehouse G, Sieberhagan C, Patch D, Naoumov N, Dhanda A, Forrest E, Thursz M. IL-1 Signal Inhibition in Alcohol-Related Hepatitis: A Randomized, Double-Blind, Placebo-Controlled Trial of Canakinumab. Clin Gastroenterol Hepatol. 2025 Apr;23(5):797-807.e5. doi: 10.1016/j.cgh.2024.07.025. Epub 2024 Aug 23.
PubMed 39181422
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- IL-1 Signal Inhibition in Alcoholic Hepatitis (ISAIAH)
- ClinicalTrials.gov ID
- NCT03775109
- Acronym / sponsor ID
- ISAIAH / 17SM4152
- Conditions
- Alcoholic Hepatitis
- Keywords
- Canakinumab, Alcoholic Hepatitis, Alcohol Use Disorder, Interleukin, Treatment, Ilaris, Liver disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- 12 Feb 2019 (actual)
- Primary completion
- 31 Mar 2023 (actual)
- Study completion
- 31 Mar 2023 (actual)
- First posted
- 13 Dec 2018 (actual)
- Results
- Posted 11 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Canakinumab 150mg/ml solution for injection | Active comparator | Drug: Canakinumab 150mg/ml solution for injection150mg/ml solution for injection |
| Dextrose | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male and female patients aged 18 years or older at screening
- Clinical diagnosis of alcoholic hepatitis at screening:
- 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).
Key exclusion criteria (23 listed)
- 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 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Canakinumab 150mg/ml solution for injectionCanakinumab 150mg/ml solution for injection | Drug | Canakinumab 150mg/ml solution for injection |
| Placebo100ml 5% Dextrose | Drug | Dextrose |
Primary outcome
Number of Patients Presenting Histological Improvement of Alcoholic Hepatitis on Liver Biopsy After 28 Days of Treatment Compared to Baseline.
Time frame: Baseline and 28 days
Histological improvement is defined as a reduction in lobular inflammation (regardless of cell type).
30 secondary outcomes
Difference in Proportions of Participants With Improvement of Polymorphonuclear Cell Infiltrate From Baseline to Day 28.
Time frame: Baseline and 28 days
Number of Patients Presenting Changes in Degree of Fibrosis (AHHS) From Baseline to Day 28
Time frame: Baseline and 28 days
Number of Participants Presenting Changes in Steatosis Grade (NAS) From Baseline to Day 28
Time frame: 28 days
Number of Participants Presenting Changes in Hepatic Venous Pressure Gradient (HVPG) Between Baseline and Day 28
Time frame: 28 days
Number of Participants Presenting Changes in Serum CK18-M30/M65 From Baseline to Day 7, 14, 21, 28, 42 and 90
Time frame: Baseline and 7, 14, 21, 28, 42, 90 days
Change in Serum Bilirubin Concentration From Baseline to Day 28
Time frame: 28 days
Change in MELD (Model For End-Stage Liver Disease) Score at From Baseline to Day 28
Time frame: Day 0 to day 28
Change in Glasgow Alcoholic Hepatitis Score (GAHS) From Day 28
Time frame: Day 0 to day 28
Change in Maddrey's Discriminant Function (mDF) Score From Baseline to Day 28
Time frame: 28 days
Lille Score at Day 7
Time frame: 7 days
Number of Patients With Resolution of Systemic Inflammatory Response Syndrome (SIRS) at Day 28 in Patients With SIRS at Baseline
Time frame: 28 days
Number of Patients With Incidence of Systemic Inflammatory Response Syndrome (SIRS) at Day 28 in Patients Without SIRS at Baseline
Time frame: 28 days
Number of Deaths at Day 90
Time frame: 90 days
Number of Patients With Infection Over 90 Days
Time frame: 90 days
Number of Patients With Acute Kidney Injury Over 90 Days
Time frame: 90 days
Number of Patients With Variceal Haemorrhage Over 90 Days
Time frame: 90 days
Number of Participants With Treatment-related Adverse Events
Time frame: 90 days
Serum and Plasma Biomarkers of Hepatic Function and Inflammation Including Cytokine Profiles Which May Indicate the Degree of Response to IL-1b Inhibition.
Time frame: 90 days
CRP Levels at Day 28
Time frame: 28 days
Length of Hospital Stay
Time frame: 90 days
Difference in Proportions of Participants With Improvement of Ballooned Hepatocytes Between Treatment Groups.
Time frame: Day 28
Difference in Proportions of Improvement of Steatosis Between Treatment Groups at Day 28
Time frame: Day 28
Number of Patients Presenting Changes in Degree of Neutrophil Infiltration (AHHS) From Baseline to Day 28
Time frame: day 28
Number of Patients Presenting Changes in Presence of Megamitochondria (AHHS) From Baseline to Day 28
Time frame: day 28
Number of Patients Presenting Changes in Type of Bilirubinostasis (AHHS) From Baseline to Day 28
Time frame: day 28
Number of Patients Presenting Changes in Lobular Inflammation (NAS) From Baseline to Day 28
Time frame: day 28
Number of Patients Presenting Changes in Hepatocyte Ballooning (NAS) From Baseline to Day 28
Time frame: day 28
Number of Patients With Sepsis Over 90 Days
Time frame: 90 days
Number of Patients With Ascites Over 90 Days
Time frame: 90 days
Number of Patients With Encephalopathy Over 90 Days
Time frame: 90 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 34763711Vergis N, Patel V, Bogdanowicz K, Czyzewska-Khan J, Fiorentino F, Day E, Cross M, Foster N, Lord E, Goldin R, Forrest E, Thursz M. IL-1 Signal Inhibition In Alcoholic Hepatitis (ISAIAH): a study protocol for a multicentre, randomised, placebo-controlled trial to explore the potential benefits of canakinumab in the treatment of alcoholic hepatitis. Trials. 2021 Nov 11;22(1):792. doi: 10.1186/s13063-021-05719-2.
- Derived from this study: PubMed 39181422Vergis N, Patel V, Bogdanowicz K, Czyzewska-Khan J, Keshinro R, Fiorentino F, Day E, Middleton P, Atkinson S, Tranah T, Cross M, Babalis D, Foster N, Lord E, Quaglia A, Lloyd J, Goldin R, Rosenberg W, Parker R, Richardson P, Masson S, Whitehouse G, Sieberhagan C, Patch D, Naoumov N, Dhanda A, Forrest E, Thursz M. IL-1 Signal Inhibition in Alcohol-Related Hepatitis: A Randomized, Double-Blind, Placebo-Controlled Trial of Canakinumab. Clin Gastroenterol Hepatol. 2025 Apr;23(5):797-807.e5. doi: 10.1016/j.cgh.2024.07.025. Epub 2024 Aug 23.
- Individual participant dataSharing planned: No
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RecruitingObservational study
Blood Collection Biorepository for Liver Disease Research
Non-Alcoholic Steatohepatitis(NASH), Hepatitis C
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Thursz study director
Imperial College London
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Canakinumab 150mg/ml solution for injection in people with Alcoholic Hepatitis, run by Imperial College London at 16 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients Presenting Histological Improvement of Alcoholic Hepatitis on Liver Biopsy After 28 Days of Treatment Compared to Baseline. (time frame: Baseline and 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03775109, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Mar 2025; AzTrials last refreshed its copy on 7 Nov 2026.