Alcoholic Hepatitis (AH)
Conditions
Keywords
Cirrhosis, Prednisone, Jaundice
Brief summary
The primary objective of this study is to evaluate the safety and tolerability of selonsertib (GS-4997) in combination with prednisolone versus prednisolone alone in participants with severe alcoholic hepatitis (AH).
Interventions
DRUGSelonsertib
18 mg tablet administered orally once daily
DRUGPrednisolone
40 mg (4 x 10 mg tablets) administered orally once daily
DRUGPlacebo
Selonsertib placebo tablet administered orally once daily
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Willing and able to give informed consent prior to any study specific procedures being performed. In individuals with hepatic encephalopathy (HE) which may impair decision-making, consent will be obtained per hospital procedures (eg, by Legally Authorized Representative) * Clinical diagnosis of severe AH * Maddrey's Discriminant Function (DF) ≥ 32 at screening Key
Exclusion criteria
* Pregnant or lactating females; * Other causes of liver disease including chronic hepatitis B (hepatitis B surface antigen \[HBsAg\] positive), chronic hepatitis C (HCV RNA positive), acetaminophen hepatotoxicity, biliary obstruction, and autoimmune liver disease; * Serum aspartate aminotransferase (AST) \>400 U/L or alanine aminotransferase (ALT) \>300 U/L; * Model for End Stage Liver Disease (MELD) \>30 at screening; * Maddrey's DF \>60 at screening; * Grade 4 Hepatic Encephalopathy (HE) by West Haven criteria; * Concomitant or previous history of hepatocellular carcinoma; * History of liver transplantation; * HIV Ab positive; * Clinical suspicion of pneumonia; * Uncontrolled sepsis; * Uncontrolled gastrointestinal (GI) bleeding or controlled GI bleeding within 7 days of screening that was associated with shock or required transfusion of more than 3 units of blood; * Type 1 hepatorenal syndrome (HRS) or renal failure defined as a serum creatinine \>221 μmol/L (\>2.5 mg/dL) or the requirement for renal replacement therapy; * Individuals dependent on inotropic (eg, epinephrine or norepinephrine) or ventilatory support (ie, endotracheal intubation or positive-pressure ventilation); * Portal vein thrombosis; * Acute pancreatitis; * Cessation of alcohol consumption for more than 2 months before Baseline/ Day 1 Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Treatment-Emergent (TE) Adverse Events (AE), Serious AEs (SAE), AEs Leading to Premature Study Drug Discontinuation, and Grade 3 or 4 Laboratory Abnormalities | Up to Day 28 plus 30 days | An AE was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect. Laboratory toxicity grading was based on Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Died by Week 8 | Week 8 | The percentage of participants who died by Week 8 was calculated. |
| Percentage of Participants Who Died by Week 12 | Week 12 | The percentage of participants who died by Week 12 was calculated. |
| Percentage of Participants Who Died by Week 24 | Week 24 | The percentage of participants who died by Week 24 was calculated. |
| Percentage of Participants With Survival at Day 28 Using Kaplan-Meier | Day 28 | The percentage of participants with survival at Day 28 using Kaplan-Meier was calculated. |
| Percentage of Participants With Survival at Week 8 Using Kaplan-Meier | Week 8 | The percentage of participants with survival at Week 8 using Kaplan-Meier was calculated. |
| Percentage of Participants With Survival at Week 12 Using Kaplan-Meier | Week 12 | The percentage of participants with survival at Week 12 using Kaplan-Meier was calculated. |
| Percentage of Participants With Survival at Week 24 Using Kaplan-Meier | Week 24 | The percentage of participants with survival at Week 24 using Kaplan-Meier was calculated. |
| Percentage of Participants Who Received a Liver Transplant | Day 28, Week 8, Week 12, and Week 24 | The percentage of participants who received a liver transplant by week 24 was calculated. |
| Percentage of Participants With Hepatorenal Syndrome (HRS) | Up to 24 weeks | The occurrence of HRS was confirmed based on the following diagnostic criteria from the International Ascites Club (IAC): 1) Cirrhosis with ascites, 2) Diagnosis of acute kidney injury (AKI) according to the ICA-AKI criteria, 3) Absence of shock, 4) No current or recent treatment with nephrotoxic drugs, and 5) Absence of parenchymal renal disease as indicated by proteinuria \>500 mg/day, microhematuria (\> 50 red blood cells per high power field) and/or abnormal renal ultrasonography. |
| Percentage of Participants With Infection | Up to 24 weeks | The occurrence of bacterial, fungal, or viral infections was recorded. An infection was considered definite in participants with clinical evidence of infection and a positive culture from a normally sterile source (with the exception of spontaneous bacterial peritonitis). |
| Length of Hospital Stay | Up to 24 weeks | Length of initial hospital stay from first dose date of study drug was calculated for participants who were released from initial hospitalization separately from those who died during their initial hospitalization. |
| Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT) | Baseline (Day 1) and up to 24 weeks | Change from Baseline was calculated as the value at endpoint minus the value at Baseline. |
| Percentage of Participants Who Died by Day 28 | Day 28 | The percentage of participants who died by Day 28 was calculated. |
| Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT) | Baseline (Day 1) and up to 24 weeks | Change from Baseline was calculated as the value at endpoint minus the value at Baseline. |
| Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase | Baseline (Day 1) and up to 24 weeks | Change from Baseline was calculated as the value at endpoint minus the value at Baseline. |
| Change From Baseline in Liver Biochemistry Tests: Bilirubin | Baseline (Day 1) and up to 24 weeks | Change from Baseline was calculated as the value at endpoint minus the value at Baseline. |
| Change From Baseline in Liver Biochemistry Tests: Albumin | Baseline (Day 1) and up to 24 weeks | Change from Baseline was calculated as the value at endpoint minus the value at Baseline. |
| Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR) | Baseline (Day 1) and up to 24 weeks | Change from Baseline was calculated as the value at endpoint minus the value at Baseline. |
| Percentage of Participants With Lille Response (Score < 0.45) at Day 7 | Day 7 | The Lille score is a tool used to predict which participants with severe alcoholic hepatitis (AH) were not responding to corticosteroid therapy. It ranges between 0 and 1, with low scores (\< 0.16) indicating complete response or positive response to steroids (continue therapy) and high scores (≥ 0.56) indicating no response or poor response to steroids (stop therapy). The Lille score was calculated using baseline factors: age, albumin, total bilirubin, serum creatinine, prothrombin time; and the change in total bilirubin between baseline (Day 1) and Day 7. Lille response was defined as having a Lille score \< 0.45. |
| Percentage of Participants With a Lille Null Response (Score ≥ 0.56) at Day 7 | Day 7 | The Lille score is a tool used to predict which participants with severe AH were not responding to corticosteroid therapy. It ranges between 0 and 1, with low scores (\< 0.16) indicating complete response or positive response to steroids (continue therapy) and high scores (≥ 0.56) indicating no response or poor response to steroids (stop therapy). The Lille score was calculated using baseline factors: age, albumin, total bilirubin, serum creatinine, prothrombin time; and the change in total bilirubin between baseline (Day 1) and Day 7. Lille null response was defined as having a Lille score ≥ 0.56. |
| Lille Score at Day 7 as a Continuous Variable | Day 7 | The Lille score is a tool used to predict which participants with severe AH were not responding to corticosteroid therapy. It ranges between 0 and 1, with low scores (\< 0.16) indicating complete response or positive response to steroids (continue therapy) and high scores (≥ 0.56) indicating no response or poor response to steroids (stop therapy). The Lille score was calculated using baseline factors: age, albumin, total bilirubin, serum creatinine, prothrombin time; and the change in total bilirubin between baseline (Day 1) and Day 7. |
| Percentage of Participants With Estimated Mortality at Month 2 and Month 6: Combined Scoring Including Lille Score at Day 7 and Baseline Model for End-Stage Liver Disease (MELD) Score | Baseline and Day 7 Time Points used to calculate Overall Mortality Risk at Months 2 and 6 | The Lille score is a tool used to predict which participants with severe AH were not responding to corticosteroid therapy. It ranges between 0 and 1, with low scores (\< 0.16) indicating complete response or positive response to steroids (continue therapy) and high scores (≥ 0.56) indicating no response or poor response to steroids (stop therapy). MELD scores are used to assess prognosis and suitability for liver transplantation. Scores can range from 6 to 40, with higher scores indicating greater disease severity. A scoring system combining the Lille score at Day 7 and the baseline MELD score was used to calculate the percentage of participants expected to die by Month 2 and by Month 6. |
| Change From Baseline in Prognostic Index: Model for End-Stage Liver Disease (MELD) Score | Baseline (Day 1) and up to 24 weeks | MELD scores are used to assess prognosis and suitability for liver transplantation. Scores can range from 6 to 40, with higher scores indicating greater disease severity. Change from Baseline was calculated as the value at endpoint minus the value at Baseline. |
| Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score | Baseline (Day 1) and up to 24 weeks | CPT scores are used to assess the severity of cirrhosis. Scores can range from 5 to 15, with higher scores indicating a greater severity of disease |
| Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score | Baseline (Day 1) and up to 24 weeks | Baseline Maddrey DF score is a prognostic tool used to determine the next step of treatment based on the severity of AH. Maddrey DF score of \< 32 indicates mild to moderate AH and a lower chance of death in the next few months. Maddrey DF score of ≥ 32 indicates severe AH and a higher chance of death in the next few months. The score has no bounds. |
| Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST) | Baseline (Day 1) and up to 24 weeks | Change from Baseline was calculated as the value at endpoint minus the value at Baseline. |
Countries
Austria, Belgium, Canada, France, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in Europe and North America. The first participant was screened on 01 September 2016. The last study visit occurred on 31 May 2018.
Pre-assignment details
166 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Selonsertib + Prednisolone Participants received selonsertib (GS-4997) 18 mg tablet orally once daily + prednisolone 40 mg (4 x 10 mg tablets) orally once daily for 28 days. | 50 |
| Placebo + Prednisolone Participants received placebo-to-match selonsertib 18 mg tablet orally once daily + prednisolone 40 mg (4 x 10 mg tablets) orally once daily for 28 days. | 52 |
| Total | 102 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Death | 12 | 8 |
| Overall Study | Investigator's Discretion | 2 | 0 |
| Overall Study | Liver Biopsy Inconsistent With Diagnosis | 2 | 0 |
| Overall Study | Lost to Follow-up | 4 | 2 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Subjects Randomized but Never Treated | 2 | 0 |
| Overall Study | Withdrew Consent | 3 | 2 |
Baseline characteristics
| Characteristic | Placebo + Prednisolone | Total | Selonsertib + Prednisolone |
|---|---|---|---|
| Age, Continuous | 49 Years STANDARD_DEVIATION 9.3 | 49 Years STANDARD_DEVIATION 9.6 | 49 Years STANDARD_DEVIATION 10 |
| Alanine Aminotransferase (ALT) | 48 Units per liter (U/L) STANDARD_DEVIATION 23.2 | 46 Units per liter (U/L) STANDARD_DEVIATION 28.5 | 45 Units per liter (U/L) STANDARD_DEVIATION 33.5 |
| Albumin | 3.0 Grams per deciltre (g/dL) STANDARD_DEVIATION 0.53 | 3.0 Grams per deciltre (g/dL) STANDARD_DEVIATION 0.58 | 3.1 Grams per deciltre (g/dL) STANDARD_DEVIATION 0.62 |
| Alkaline Phosphatase | 189 U/L STANDARD_DEVIATION 111.3 | 176 U/L STANDARD_DEVIATION 91.4 | 162 U/L STANDARD_DEVIATION 62.2 |
| Aspartate Aminotransferase (AST) | 129 U/L STANDARD_DEVIATION 59.9 | 126 U/L STANDARD_DEVIATION 60.2 | 122 U/L STANDARD_DEVIATION 60.9 |
| Baseline Infection No | 41 Participants | 85 Participants | 44 Participants |
| Baseline Infection Yes | 11 Participants | 17 Participants | 6 Participants |
| Bilirubin | 14.5 Milligrams per deciliter (mg/dL) STANDARD_DEVIATION 7.78 | 14.4 Milligrams per deciliter (mg/dL) STANDARD_DEVIATION 8.02 | 14.3 Milligrams per deciliter (mg/dL) STANDARD_DEVIATION 8.35 |
| Child-Pugh-Turcotte (CPT) Score | 10 Units on a scale STANDARD_DEVIATION 1.3 | 10 Units on a scale STANDARD_DEVIATION 1.2 | 10 Units on a scale STANDARD_DEVIATION 1.2 |
| Days Hospitalized Prior to First Dose Date | 10 Days STANDARD_DEVIATION 5.2 | 10 Days STANDARD_DEVIATION 4.9 | 10 Days STANDARD_DEVIATION 4.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 49 Participants | 95 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 5 Participants | 3 Participants |
| Gamma Glutamyl Transferase (GGT) | 278 U/L STANDARD_DEVIATION 358.7 | 259 U/L STANDARD_DEVIATION 285 | 238 U/L STANDARD_DEVIATION 175.5 |
| Hospitalized at Time of Screening No | 4 Participants | 8 Participants | 4 Participants |
| Hospitalized at Time of Screening Yes | 48 Participants | 94 Participants | 46 Participants |
| International Normalized Ratio (INR) | 1.6 Ratio STANDARD_DEVIATION 0.22 | 1.6 Ratio STANDARD_DEVIATION 0.27 | 1.7 Ratio STANDARD_DEVIATION 0.31 |
| Maddrey Discriminant Function (DF) Score | 38 Units on a scale STANDARD_DEVIATION 11.4 | 40 Units on a scale STANDARD_DEVIATION 14.2 | 42 Units on a scale STANDARD_DEVIATION 16.9 |
| Model for End-Stage Liver Disease (MELD) Score | 22 Units on a scale STANDARD_DEVIATION 4.4 | 22 Units on a scale STANDARD_DEVIATION 4.3 | 22 Units on a scale STANDARD_DEVIATION 4.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 6 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) White | 44 Participants | 88 Participants | 44 Participants |
| Sex: Female, Male Female | 16 Participants | 37 Participants | 21 Participants |
| Sex: Female, Male Male | 36 Participants | 65 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 14 / 50 | 9 / 52 |
| other Total, other adverse events | 43 / 50 | 42 / 52 |
| serious Total, serious adverse events | 25 / 50 | 21 / 52 |
Outcome results
Primary
Percentage of Participants With Treatment-Emergent (TE) Adverse Events (AE), Serious AEs (SAE), AEs Leading to Premature Study Drug Discontinuation, and Grade 3 or 4 Laboratory Abnormalities
An AE was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect. Laboratory toxicity grading was based on Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03.
Time frame: Up to Day 28 plus 30 days
Population: Safety Analysis Set included participants who were randomized and took at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Selonsertib + Prednisolone | Percentage of Participants With Treatment-Emergent (TE) Adverse Events (AE), Serious AEs (SAE), AEs Leading to Premature Study Drug Discontinuation, and Grade 3 or 4 Laboratory Abnormalities | TEAEs | 94.0 Percentage of participants |
| Selonsertib + Prednisolone | Percentage of Participants With Treatment-Emergent (TE) Adverse Events (AE), Serious AEs (SAE), AEs Leading to Premature Study Drug Discontinuation, and Grade 3 or 4 Laboratory Abnormalities | TE SAEs | 50.0 Percentage of participants |
| Selonsertib + Prednisolone | Percentage of Participants With Treatment-Emergent (TE) Adverse Events (AE), Serious AEs (SAE), AEs Leading to Premature Study Drug Discontinuation, and Grade 3 or 4 Laboratory Abnormalities | TEAEs (discontinuation of Selonsertib/Placebo) | 18.0 Percentage of participants |
| Selonsertib + Prednisolone | Percentage of Participants With Treatment-Emergent (TE) Adverse Events (AE), Serious AEs (SAE), AEs Leading to Premature Study Drug Discontinuation, and Grade 3 or 4 Laboratory Abnormalities | TEAEs (discontinuation of Prednisolone) | 14.0 Percentage of participants |
| Selonsertib + Prednisolone | Percentage of Participants With Treatment-Emergent (TE) Adverse Events (AE), Serious AEs (SAE), AEs Leading to Premature Study Drug Discontinuation, and Grade 3 or 4 Laboratory Abnormalities | TEAEs (discontinuation of both drugs in regimen) | 14.0 Percentage of participants |
| Selonsertib + Prednisolone | Percentage of Participants With Treatment-Emergent (TE) Adverse Events (AE), Serious AEs (SAE), AEs Leading to Premature Study Drug Discontinuation, and Grade 3 or 4 Laboratory Abnormalities | Laboratory abnormalities (Grade 3 or 4) | 72.0 Percentage of participants |
| Selonsertib + Prednisolone | Percentage of Participants With Treatment-Emergent (TE) Adverse Events (AE), Serious AEs (SAE), AEs Leading to Premature Study Drug Discontinuation, and Grade 3 or 4 Laboratory Abnormalities | Laboratory abnormalities (Grade 3) | 42.0 Percentage of participants |
| Selonsertib + Prednisolone | Percentage of Participants With Treatment-Emergent (TE) Adverse Events (AE), Serious AEs (SAE), AEs Leading to Premature Study Drug Discontinuation, and Grade 3 or 4 Laboratory Abnormalities | Laboratory abnormalities (Grade 4) | 30.0 Percentage of participants |
| Placebo + Prednisolone | Percentage of Participants With Treatment-Emergent (TE) Adverse Events (AE), Serious AEs (SAE), AEs Leading to Premature Study Drug Discontinuation, and Grade 3 or 4 Laboratory Abnormalities | Laboratory abnormalities (Grade 4) | 20.0 Percentage of participants |
| Placebo + Prednisolone | Percentage of Participants With Treatment-Emergent (TE) Adverse Events (AE), Serious AEs (SAE), AEs Leading to Premature Study Drug Discontinuation, and Grade 3 or 4 Laboratory Abnormalities | TEAEs | 94.2 Percentage of participants |
| Placebo + Prednisolone | Percentage of Participants With Treatment-Emergent (TE) Adverse Events (AE), Serious AEs (SAE), AEs Leading to Premature Study Drug Discontinuation, and Grade 3 or 4 Laboratory Abnormalities | TEAEs (discontinuation of both drugs in regimen) | 7.7 Percentage of participants |
| Placebo + Prednisolone | Percentage of Participants With Treatment-Emergent (TE) Adverse Events (AE), Serious AEs (SAE), AEs Leading to Premature Study Drug Discontinuation, and Grade 3 or 4 Laboratory Abnormalities | TE SAEs | 40.4 Percentage of participants |
| Placebo + Prednisolone | Percentage of Participants With Treatment-Emergent (TE) Adverse Events (AE), Serious AEs (SAE), AEs Leading to Premature Study Drug Discontinuation, and Grade 3 or 4 Laboratory Abnormalities | Laboratory abnormalities (Grade 3) | 52.0 Percentage of participants |
| Placebo + Prednisolone | Percentage of Participants With Treatment-Emergent (TE) Adverse Events (AE), Serious AEs (SAE), AEs Leading to Premature Study Drug Discontinuation, and Grade 3 or 4 Laboratory Abnormalities | TEAEs (discontinuation of Selonsertib/Placebo) | 7.7 Percentage of participants |
| Placebo + Prednisolone | Percentage of Participants With Treatment-Emergent (TE) Adverse Events (AE), Serious AEs (SAE), AEs Leading to Premature Study Drug Discontinuation, and Grade 3 or 4 Laboratory Abnormalities | Laboratory abnormalities (Grade 3 or 4) | 72.0 Percentage of participants |
| Placebo + Prednisolone | Percentage of Participants With Treatment-Emergent (TE) Adverse Events (AE), Serious AEs (SAE), AEs Leading to Premature Study Drug Discontinuation, and Grade 3 or 4 Laboratory Abnormalities | TEAEs (discontinuation of Prednisolone) | 11.5 Percentage of participants |
Secondary
Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT)
Change from Baseline was calculated as the value at endpoint minus the value at Baseline.
Time frame: Baseline (Day 1) and up to 24 weeks
Population: Participants in the Full Analysis Set with available baseline and any postbaseline data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT) | Change at Week 1 | 26 U/L | Standard Deviation 40.7 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT) | Change at Week 2 | 31 U/L | Standard Deviation 35 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT) | Change at Week 3 | 24 U/L | Standard Deviation 32.6 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT) | Change at Week 4 | 15 U/L | Standard Deviation 28.7 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT) | Change at Week 6 | -10 U/L | Standard Deviation 19.9 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT) | Change at Week 8 | -13 U/L | Standard Deviation 18.1 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT) | Change at Week 12 | -15 U/L | Standard Deviation 19.3 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT) | Change at Week 16 | -14 U/L | Standard Deviation 21 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT) | Change at Week 20 | -12 U/L | Standard Deviation 18.6 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT) | Change at Week 24 | -12 U/L | Standard Deviation 19.4 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT) | Change at Week 16 | -21 U/L | Standard Deviation 28.6 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT) | Change at Week 1 | 29 U/L | Standard Deviation 28.2 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT) | Change at Week 8 | -20 U/L | Standard Deviation 24.6 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT) | Change at Week 2 | 36 U/L | Standard Deviation 33.6 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT) | Change at Week 24 | -22 U/L | Standard Deviation 21.8 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT) | Change at Week 3 | 24 U/L | Standard Deviation 28.8 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT) | Change at Week 12 | -17 U/L | Standard Deviation 42.9 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT) | Change at Week 4 | 12 U/L | Standard Deviation 32.6 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT) | Change at Week 20 | -24 U/L | Standard Deviation 21.7 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT) | Change at Week 6 | -18 U/L | Standard Deviation 21.8 |
Secondary
Change From Baseline in Liver Biochemistry Tests: Albumin
Change from Baseline was calculated as the value at endpoint minus the value at Baseline.
Time frame: Baseline (Day 1) and up to 24 weeks
Population: Participants in the Full Analysis Set with available baseline and any postbaseline data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Albumin | Change at Week 1 | 0.2 g/dL | Standard Deviation 0.45 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Albumin | Change at Week 2 | 0.3 g/dL | Standard Deviation 0.47 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Albumin | Change at Week 3 | 0.3 g/dL | Standard Deviation 0.58 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Albumin | Change at Week 4 | 0.4 g/dL | Standard Deviation 0.63 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Albumin | Change at Week 6 | 0.2 g/dL | Standard Deviation 0.82 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Albumin | Change at Week 8 | 0.3 g/dL | Standard Deviation 0.8 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Albumin | Change at Week 12 | 0.5 g/dL | Standard Deviation 0.82 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Albumin | Change at Week 16 | 0.5 g/dL | Standard Deviation 0.95 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Albumin | Change at Week 20 | 0.8 g/dL | Standard Deviation 0.92 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Albumin | Change at Week 24 | 0.8 g/dL | Standard Deviation 0.76 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Albumin | Change at Week 16 | 0.7 g/dL | Standard Deviation 0.64 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Albumin | Change at Week 1 | 0.2 g/dL | Standard Deviation 0.31 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Albumin | Change at Week 8 | 0.6 g/dL | Standard Deviation 0.66 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Albumin | Change at Week 2 | 0.4 g/dL | Standard Deviation 0.45 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Albumin | Change at Week 24 | 0.8 g/dL | Standard Deviation 0.68 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Albumin | Change at Week 3 | 0.4 g/dL | Standard Deviation 0.54 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Albumin | Change at Week 12 | 0.6 g/dL | Standard Deviation 0.68 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Albumin | Change at Week 4 | 0.5 g/dL | Standard Deviation 0.57 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Albumin | Change at Week 20 | 0.8 g/dL | Standard Deviation 0.68 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Albumin | Change at Week 6 | 0.4 g/dL | Standard Deviation 0.67 |
Secondary
Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase
Change from Baseline was calculated as the value at endpoint minus the value at Baseline.
Time frame: Baseline (Day 1) and up to 24 weeks
Population: Participants in the Full Analysis Set with available baseline and any postbaseline data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase | Change at Week 3 | 10 U/L | Standard Deviation 68.7 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase | Change at Week 8 | -14 U/L | Standard Deviation 52.6 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase | Change at Week 2 | 23 U/L | Standard Deviation 70.7 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase | Change at Week 12 | -35 U/L | Standard Deviation 65 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase | Change at Week 4 | 8 U/L | Standard Deviation 71.7 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase | Change at Week 16 | -26 U/L | Standard Deviation 83.1 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase | Change at Week 1 | 11 U/L | Standard Deviation 55.3 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase | Change at Week 20 | -29 U/L | Standard Deviation 83.3 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase | Change at Week 6 | 1 U/L | Standard Deviation 65.3 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase | Change at Week 24 | -25 U/L | Standard Deviation 87.3 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase | Change at Week 6 | -21 U/L | Standard Deviation 69.8 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase | Change at Week 1 | -3 U/L | Standard Deviation 63.6 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase | Change at Week 2 | -5 U/L | Standard Deviation 70.6 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase | Change at Week 3 | -4 U/L | Standard Deviation 89.8 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase | Change at Week 4 | -16 U/L | Standard Deviation 89.8 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase | Change at Week 24 | -43 U/L | Standard Deviation 101 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase | Change at Week 8 | -47 U/L | Standard Deviation 97.8 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase | Change at Week 12 | -52 U/L | Standard Deviation 102.8 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase | Change at Week 16 | -50 U/L | Standard Deviation 92.8 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase | Change at Week 20 | -45 U/L | Standard Deviation 106.8 |
Secondary
Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST)
Change from Baseline was calculated as the value at endpoint minus the value at Baseline.
Time frame: Baseline (Day 1) and up to 24 weeks
Population: Participants in the Full Analysis Set with available baseline and any postbaseline data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST) | Change at Week 1 | -2 U/L | Standard Deviation 66.9 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST) | Change at Week 2 | -17 U/L | Standard Deviation 58.5 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST) | Change at Week 3 | -34 U/L | Standard Deviation 38.4 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST) | Change at Week 4 | -45 U/L | Standard Deviation 35.8 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST) | Change at Week 6 | -54 U/L | Standard Deviation 45.6 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST) | Change at Week 8 | -48 U/L | Standard Deviation 46.6 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST) | Change at Week 12 | -59 U/L | Standard Deviation 45.2 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST) | Change at Week 16 | -59 U/L | Standard Deviation 56.9 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST) | Change at Week 20 | -57 U/L | Standard Deviation 46.9 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST) | Change at Week 24 | -59 U/L | Standard Deviation 49.6 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST) | Change at Week 16 | -70 U/L | Standard Deviation 76.4 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST) | Change at Week 1 | 4 U/L | Standard Deviation 52.8 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST) | Change at Week 8 | -61 U/L | Standard Deviation 63.5 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST) | Change at Week 2 | -11 U/L | Standard Deviation 52.9 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST) | Change at Week 24 | -68 U/L | Standard Deviation 59.4 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST) | Change at Week 3 | -39 U/L | Standard Deviation 54 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST) | Change at Week 12 | -63 U/L | Standard Deviation 86.5 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST) | Change at Week 4 | -55 U/L | Standard Deviation 60.2 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST) | Change at Week 20 | -64 U/L | Standard Deviation 72.6 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST) | Change at Week 6 | -74 U/L | Standard Deviation 60 |
Secondary
Change From Baseline in Liver Biochemistry Tests: Bilirubin
Change from Baseline was calculated as the value at endpoint minus the value at Baseline.
Time frame: Baseline (Day 1) and up to 24 weeks
Population: Participants in the Full Analysis Set with available baseline and any postbaseline data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Bilirubin | Change at Week 1 | -2.1 mg/dL | Standard Deviation 3.99 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Bilirubin | Change at Week 16 | -9.4 mg/dL | Standard Deviation 8.35 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Bilirubin | Change at Week 2 | -2.9 mg/dL | Standard Deviation 5.34 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Bilirubin | Change at Week 3 | -4.8 mg/dL | Standard Deviation 7.68 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Bilirubin | Change at Week 4 | -6.3 mg/dL | Standard Deviation 6.01 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Bilirubin | Change at Week 6 | -8.7 mg/dL | Standard Deviation 8.22 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Bilirubin | Change at Week 8 | -8.4 mg/dL | Standard Deviation 7.53 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Bilirubin | Change at Week 12 | -9.5 mg/dL | Standard Deviation 7.86 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Bilirubin | Change at Week 20 | -8.1 mg/dL | Standard Deviation 9.88 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Bilirubin | Change at Week 24 | -9.4 mg/dL | Standard Deviation 7.72 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Bilirubin | Change at Week 12 | -11.2 mg/dL | Standard Deviation 7.79 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Bilirubin | Change at Week 1 | -4.3 mg/dL | Standard Deviation 3.46 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Bilirubin | Change at Week 6 | -9.3 mg/dL | Standard Deviation 7.4 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Bilirubin | Change at Week 16 | -11.3 mg/dL | Standard Deviation 8.37 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Bilirubin | Change at Week 24 | -10.7 mg/dL | Standard Deviation 8.09 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Bilirubin | Change at Week 2 | -6.3 mg/dL | Standard Deviation 4.99 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Bilirubin | Change at Week 8 | -10.3 mg/dL | Standard Deviation 7.36 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Bilirubin | Change at Week 3 | -7.2 mg/dL | Standard Deviation 6.21 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Bilirubin | Change at Week 20 | -11.3 mg/dL | Standard Deviation 7.94 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Bilirubin | Change at Week 4 | -8.6 mg/dL | Standard Deviation 6.52 |
Secondary
Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT)
Change from Baseline was calculated as the value at endpoint minus the value at Baseline.
Time frame: Baseline (Day 1) and up to 24 weeks
Population: Participants in the Full Analysis Set with available baseline and any postbaseline data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT) | Change at Week 1 | 3 U/L | Standard Deviation 79.2 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT) | Change at Week 2 | 9 U/L | Standard Deviation 140.8 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT) | Change at Week 3 | -12 U/L | Standard Deviation 170.2 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT) | Change at Week 4 | -7 U/L | Standard Deviation 169.3 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT) | Change at Week 6 | -61 U/L | Standard Deviation 139.7 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT) | Change at Week 8 | -96 U/L | Standard Deviation 137.7 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT) | Change at Week 12 | -105 U/L | Standard Deviation 136.1 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT) | Change at Week 16 | -87 U/L | Standard Deviation 157.4 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT) | Change at Week 20 | -134 U/L | Standard Deviation 150.9 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT) | Change at Week 24 | -131 U/L | Standard Deviation 154.4 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT) | Change at Week 16 | -114 U/L | Standard Deviation 251.3 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT) | Change at Week 1 | -1 U/L | Standard Deviation 192.5 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT) | Change at Week 8 | -121 U/L | Standard Deviation 314.2 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT) | Change at Week 2 | 9 U/L | Standard Deviation 189 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT) | Change at Week 24 | -54 U/L | Standard Deviation 277 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT) | Change at Week 3 | 9 U/L | Standard Deviation 197.1 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT) | Change at Week 12 | -100 U/L | Standard Deviation 274 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT) | Change at Week 4 | -5 U/L | Standard Deviation 284 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT) | Change at Week 20 | -85 U/L | Standard Deviation 342.9 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT) | Change at Week 6 | -72 U/L | Standard Deviation 173.4 |
Secondary
Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR)
Change from Baseline was calculated as the value at endpoint minus the value at Baseline.
Time frame: Baseline (Day 1) and up to 24 weeks
Population: Participants in the Full Analysis Set with available baseline and any postbaseline data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR) | Change at Week 1 | -0.1 Ratio | Standard Deviation 0.28 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR) | Change at Week 2 | -0.2 Ratio | Standard Deviation 0.32 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR) | Change at Week 3 | -0.3 Ratio | Standard Deviation 0.38 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR) | Change at Week 4 | -0.3 Ratio | Standard Deviation 0.36 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR) | Change at Week 6 | -0.2 Ratio | Standard Deviation 0.4 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR) | Change at Week 8 | -0.3 Ratio | Standard Deviation 0.43 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR) | Change at Week 12 | -0.3 Ratio | Standard Deviation 0.41 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR) | Change at Week 16 | -0.3 Ratio | Standard Deviation 0.4 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR) | Change at Week 20 | -0.3 Ratio | Standard Deviation 0.42 |
| Selonsertib + Prednisolone | Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR) | Change at Week 24 | -0.4 Ratio | Standard Deviation 0.36 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR) | Change at Week 16 | -0.3 Ratio | Standard Deviation 0.22 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR) | Change at Week 1 | -0.1 Ratio | Standard Deviation 0.16 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR) | Change at Week 8 | -0.3 Ratio | Standard Deviation 0.19 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR) | Change at Week 2 | -0.2 Ratio | Standard Deviation 0.23 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR) | Change at Week 24 | -0.3 Ratio | Standard Deviation 0.32 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR) | Change at Week 3 | -0.2 Ratio | Standard Deviation 0.25 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR) | Change at Week 12 | -0.3 Ratio | Standard Deviation 0.19 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR) | Change at Week 4 | -0.2 Ratio | Standard Deviation 0.18 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR) | Change at Week 20 | -0.3 Ratio | Standard Deviation 0.27 |
| Placebo + Prednisolone | Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR) | Change at Week 6 | -0.2 Ratio | Standard Deviation 0.33 |
Secondary
Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score
CPT scores are used to assess the severity of cirrhosis. Scores can range from 5 to 15, with higher scores indicating a greater severity of disease
Time frame: Baseline (Day 1) and up to 24 weeks
Population: Participants in the Full Analysis Set with available baseline and any postbaseline data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Selonsertib + Prednisolone | Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score | Change at Week 1 | 0 Units on a scale | Standard Deviation 1.5 |
| Selonsertib + Prednisolone | Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score | Change at Week 2 | -1 Units on a scale | Standard Deviation 1.4 |
| Selonsertib + Prednisolone | Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score | Change at Week 3 | -1 Units on a scale | Standard Deviation 1.7 |
| Selonsertib + Prednisolone | Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score | Change at Week 4 | -1 Units on a scale | Standard Deviation 1.9 |
| Selonsertib + Prednisolone | Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score | Change at Week 6 | -1 Units on a scale | Standard Deviation 2.1 |
| Selonsertib + Prednisolone | Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score | Change at Week 8 | -2 Units on a scale | Standard Deviation 2.4 |
| Selonsertib + Prednisolone | Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score | Change at Week 12 | -2 Units on a scale | Standard Deviation 2.2 |
| Selonsertib + Prednisolone | Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score | Change at Week 16 | -2 Units on a scale | Standard Deviation 2.4 |
| Selonsertib + Prednisolone | Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score | Change at Week 20 | -3 Units on a scale | Standard Deviation 2.3 |
| Selonsertib + Prednisolone | Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score | Change at Week 24 | -3 Units on a scale | Standard Deviation 1.7 |
| Placebo + Prednisolone | Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score | Change at Week 16 | -3 Units on a scale | Standard Deviation 1.8 |
| Placebo + Prednisolone | Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score | Change at Week 1 | -1 Units on a scale | Standard Deviation 0.9 |
| Placebo + Prednisolone | Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score | Change at Week 8 | -2 Units on a scale | Standard Deviation 1.5 |
| Placebo + Prednisolone | Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score | Change at Week 2 | -1 Units on a scale | Standard Deviation 1.4 |
| Placebo + Prednisolone | Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score | Change at Week 24 | -3 Units on a scale | Standard Deviation 1.6 |
| Placebo + Prednisolone | Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score | Change at Week 3 | -1 Units on a scale | Standard Deviation 1.4 |
| Placebo + Prednisolone | Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score | Change at Week 12 | -3 Units on a scale | Standard Deviation 1.7 |
| Placebo + Prednisolone | Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score | Change at Week 4 | -2 Units on a scale | Standard Deviation 1.7 |
| Placebo + Prednisolone | Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score | Change at Week 20 | -3 Units on a scale | Standard Deviation 1.6 |
| Placebo + Prednisolone | Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score | Change at Week 6 | -2 Units on a scale | Standard Deviation 1.7 |
Secondary
Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score
Baseline Maddrey DF score is a prognostic tool used to determine the next step of treatment based on the severity of AH. Maddrey DF score of \< 32 indicates mild to moderate AH and a lower chance of death in the next few months. Maddrey DF score of ≥ 32 indicates severe AH and a higher chance of death in the next few months. The score has no bounds.
Time frame: Baseline (Day 1) and up to 24 weeks
Population: Participants in the Full Analysis Set with available baseline and any postbaseline data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Selonsertib + Prednisolone | Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score | Change at Week 2 | -13 Units on a scale | Standard Deviation 18.1 |
| Selonsertib + Prednisolone | Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score | Change at Week 6 | -20 Units on a scale | Standard Deviation 23.2 |
| Selonsertib + Prednisolone | Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score | Change at Week 1 | -8 Units on a scale | Standard Deviation 15.2 |
| Selonsertib + Prednisolone | Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score | Change at Week 3 | -17 Units on a scale | Standard Deviation 21.8 |
| Selonsertib + Prednisolone | Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score | Change at Week 4 | -19 Units on a scale | Standard Deviation 20 |
| Selonsertib + Prednisolone | Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score | Change at Week 8 | -19 Units on a scale | Standard Deviation 21.5 |
| Selonsertib + Prednisolone | Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score | Change at Week 12 | -23 Units on a scale | Standard Deviation 21.8 |
| Selonsertib + Prednisolone | Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score | Change at Week 16 | -23 Units on a scale | Standard Deviation 22.6 |
| Selonsertib + Prednisolone | Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score | Change at Week 20 | -25 Units on a scale | Standard Deviation 26.2 |
| Selonsertib + Prednisolone | Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score | Change at Week 24 | -27 Units on a scale | Standard Deviation 21.7 |
| Placebo + Prednisolone | Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score | Change at Week 16 | -23 Units on a scale | Standard Deviation 13.7 |
| Placebo + Prednisolone | Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score | Change at Week 2 | -15 Units on a scale | Standard Deviation 11.4 |
| Placebo + Prednisolone | Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score | Change at Week 4 | -19 Units on a scale | Standard Deviation 10.9 |
| Placebo + Prednisolone | Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score | Change at Week 8 | -21 Units on a scale | Standard Deviation 12 |
| Placebo + Prednisolone | Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score | Change at Week 6 | -19 Units on a scale | Standard Deviation 17.6 |
| Placebo + Prednisolone | Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score | Change at Week 24 | -22 Units on a scale | Standard Deviation 16.9 |
| Placebo + Prednisolone | Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score | Change at Week 1 | -10 Units on a scale | Standard Deviation 7.7 |
| Placebo + Prednisolone | Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score | Change at Week 12 | -23 Units on a scale | Standard Deviation 12.2 |
| Placebo + Prednisolone | Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score | Change at Week 3 | -17 Units on a scale | Standard Deviation 13.3 |
| Placebo + Prednisolone | Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score | Change at Week 20 | -23 Units on a scale | Standard Deviation 15.4 |
Secondary
Change From Baseline in Prognostic Index: Model for End-Stage Liver Disease (MELD) Score
MELD scores are used to assess prognosis and suitability for liver transplantation. Scores can range from 6 to 40, with higher scores indicating greater disease severity. Change from Baseline was calculated as the value at endpoint minus the value at Baseline.
Time frame: Baseline (Day 1) and up to 24 weeks
Population: Participants in the Full Analysis Set with available baseline and any postbaseline data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Selonsertib + Prednisolone | Change From Baseline in Prognostic Index: Model for End-Stage Liver Disease (MELD) Score | Change at Week 3 | -4 Units on a scale | Standard Deviation 4.7 |
| Selonsertib + Prednisolone | Change From Baseline in Prognostic Index: Model for End-Stage Liver Disease (MELD) Score | Change at Week 2 | -3 Units on a scale | Standard Deviation 4 |
| Selonsertib + Prednisolone | Change From Baseline in Prognostic Index: Model for End-Stage Liver Disease (MELD) Score | Change at Week 12 | -7 Units on a scale | Standard Deviation 6 |
| Selonsertib + Prednisolone | Change From Baseline in Prognostic Index: Model for End-Stage Liver Disease (MELD) Score | Change at Week 4 | -5 Units on a scale | Standard Deviation 5.2 |
| Selonsertib + Prednisolone | Change From Baseline in Prognostic Index: Model for End-Stage Liver Disease (MELD) Score | Change at Week 16 | -7 Units on a scale | Standard Deviation 6.5 |
| Selonsertib + Prednisolone | Change From Baseline in Prognostic Index: Model for End-Stage Liver Disease (MELD) Score | Change at Week 1 | -2 Units on a scale | Standard Deviation 2.9 |
| Selonsertib + Prednisolone | Change From Baseline in Prognostic Index: Model for End-Stage Liver Disease (MELD) Score | Change at Week 20 | -8 Units on a scale | Standard Deviation 7.6 |
| Selonsertib + Prednisolone | Change From Baseline in Prognostic Index: Model for End-Stage Liver Disease (MELD) Score | Change at Week 6 | -6 Units on a scale | Standard Deviation 6.1 |
| Selonsertib + Prednisolone | Change From Baseline in Prognostic Index: Model for End-Stage Liver Disease (MELD) Score | Change at Week 24 | -9 Units on a scale | Standard Deviation 6.1 |
| Selonsertib + Prednisolone | Change From Baseline in Prognostic Index: Model for End-Stage Liver Disease (MELD) Score | Change at Week 8 | -7 Units on a scale | Standard Deviation 5.9 |
| Placebo + Prednisolone | Change From Baseline in Prognostic Index: Model for End-Stage Liver Disease (MELD) Score | Change at Week 24 | -10 Units on a scale | Standard Deviation 5.6 |
| Placebo + Prednisolone | Change From Baseline in Prognostic Index: Model for End-Stage Liver Disease (MELD) Score | Change at Week 1 | -3 Units on a scale | Standard Deviation 2.6 |
| Placebo + Prednisolone | Change From Baseline in Prognostic Index: Model for End-Stage Liver Disease (MELD) Score | Change at Week 2 | -5 Units on a scale | Standard Deviation 3.5 |
| Placebo + Prednisolone | Change From Baseline in Prognostic Index: Model for End-Stage Liver Disease (MELD) Score | Change at Week 3 | -5 Units on a scale | Standard Deviation 3.9 |
| Placebo + Prednisolone | Change From Baseline in Prognostic Index: Model for End-Stage Liver Disease (MELD) Score | Change at Week 4 | -6 Units on a scale | Standard Deviation 3.9 |
| Placebo + Prednisolone | Change From Baseline in Prognostic Index: Model for End-Stage Liver Disease (MELD) Score | Change at Week 6 | -7 Units on a scale | Standard Deviation 5.2 |
| Placebo + Prednisolone | Change From Baseline in Prognostic Index: Model for End-Stage Liver Disease (MELD) Score | Change at Week 8 | -8 Units on a scale | Standard Deviation 4.7 |
| Placebo + Prednisolone | Change From Baseline in Prognostic Index: Model for End-Stage Liver Disease (MELD) Score | Change at Week 12 | -10 Units on a scale | Standard Deviation 4.8 |
| Placebo + Prednisolone | Change From Baseline in Prognostic Index: Model for End-Stage Liver Disease (MELD) Score | Change at Week 16 | -9 Units on a scale | Standard Deviation 5.5 |
| Placebo + Prednisolone | Change From Baseline in Prognostic Index: Model for End-Stage Liver Disease (MELD) Score | Change at Week 20 | -10 Units on a scale | Standard Deviation 5.4 |
Secondary
Length of Hospital Stay
Length of initial hospital stay from first dose date of study drug was calculated for participants who were released from initial hospitalization separately from those who died during their initial hospitalization.
Time frame: Up to 24 weeks
Population: Participants in the Full Analysis Set with available data were analyzed. Participants released from initial hospitalization and those who died during initial hospitalization were analyzed separately, so a total of 41 participants and 45 participants were analyzed for the Selonsertib + Prednisolone and Placebo + Prednisolone arms, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Selonsertib + Prednisolone | Length of Hospital Stay | Released from initial hospitalization | 11.0 Days | Standard Deviation 11.53 |
| Selonsertib + Prednisolone | Length of Hospital Stay | Died during initial hospitalization | 36.0 Days | Standard Deviation 18.52 |
| Placebo + Prednisolone | Length of Hospital Stay | Released from initial hospitalization | 11.0 Days | Standard Deviation 11.25 |
| Placebo + Prednisolone | Length of Hospital Stay | Died during initial hospitalization | 6.0 Days | Standard Deviation 1.41 |
Secondary
Lille Score at Day 7 as a Continuous Variable
The Lille score is a tool used to predict which participants with severe AH were not responding to corticosteroid therapy. It ranges between 0 and 1, with low scores (\< 0.16) indicating complete response or positive response to steroids (continue therapy) and high scores (≥ 0.56) indicating no response or poor response to steroids (stop therapy). The Lille score was calculated using baseline factors: age, albumin, total bilirubin, serum creatinine, prothrombin time; and the change in total bilirubin between baseline (Day 1) and Day 7.
Time frame: Day 7
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Selonsertib + Prednisolone | Lille Score at Day 7 as a Continuous Variable | 0.254 Lille score | Standard Deviation 0.2495 |
| Placebo + Prednisolone | Lille Score at Day 7 as a Continuous Variable | 0.178 Lille score | Standard Deviation 0.1534 |
Secondary
Percentage of Participants Who Died by Day 28
The percentage of participants who died by Day 28 was calculated.
Time frame: Day 28
Population: Participants in the Full Analysis Set (participants who took at least 1 dose of study drug, and had histologically-confirmed severe alcoholic hepatitis (AH)) with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selonsertib + Prednisolone | Percentage of Participants Who Died by Day 28 | 4.3 Percentage of participants |
| Placebo + Prednisolone | Percentage of Participants Who Died by Day 28 | 4.0 Percentage of participants |
p-value: 1Fisher Exact
Secondary
Percentage of Participants Who Died by Week 12
The percentage of participants who died by Week 12 was calculated.
Time frame: Week 12
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selonsertib + Prednisolone | Percentage of Participants Who Died by Week 12 | 25.6 Percentage of participants |
| Placebo + Prednisolone | Percentage of Participants Who Died by Week 12 | 10.2 Percentage of participants |
p-value: 0.06Fisher Exact
Secondary
Percentage of Participants Who Died by Week 24
The percentage of participants who died by Week 24 was calculated.
Time frame: Week 24
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selonsertib + Prednisolone | Percentage of Participants Who Died by Week 24 | 31.7 Percentage of participants |
| Placebo + Prednisolone | Percentage of Participants Who Died by Week 24 | 18.8 Percentage of participants |
p-value: 0.22Fisher Exact
Secondary
Percentage of Participants Who Died by Week 8
The percentage of participants who died by Week 8 was calculated.
Time frame: Week 8
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selonsertib + Prednisolone | Percentage of Participants Who Died by Week 8 | 20.5 Percentage of participants |
| Placebo + Prednisolone | Percentage of Participants Who Died by Week 8 | 6.1 Percentage of participants |
p-value: 0.061Fisher Exact
Secondary
Percentage of Participants Who Received a Liver Transplant
The percentage of participants who received a liver transplant by week 24 was calculated.
Time frame: Day 28, Week 8, Week 12, and Week 24
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Selonsertib + Prednisolone | Percentage of Participants Who Received a Liver Transplant | Week 12 | 3.0 Percentage of participants |
| Selonsertib + Prednisolone | Percentage of Participants Who Received a Liver Transplant | Day 28 | 2.2 Percentage of participants |
| Selonsertib + Prednisolone | Percentage of Participants Who Received a Liver Transplant | Week 24 | 6.9 Percentage of participants |
| Selonsertib + Prednisolone | Percentage of Participants Who Received a Liver Transplant | Week 8 | 2.8 Percentage of participants |
| Placebo + Prednisolone | Percentage of Participants Who Received a Liver Transplant | Week 24 | 2.6 Percentage of participants |
| Placebo + Prednisolone | Percentage of Participants Who Received a Liver Transplant | Day 28 | 0 Percentage of participants |
| Placebo + Prednisolone | Percentage of Participants Who Received a Liver Transplant | Week 12 | 0 Percentage of participants |
| Placebo + Prednisolone | Percentage of Participants Who Received a Liver Transplant | Week 8 | 0 Percentage of participants |
Secondary
Percentage of Participants With a Lille Null Response (Score ≥ 0.56) at Day 7
The Lille score is a tool used to predict which participants with severe AH were not responding to corticosteroid therapy. It ranges between 0 and 1, with low scores (\< 0.16) indicating complete response or positive response to steroids (continue therapy) and high scores (≥ 0.56) indicating no response or poor response to steroids (stop therapy). The Lille score was calculated using baseline factors: age, albumin, total bilirubin, serum creatinine, prothrombin time; and the change in total bilirubin between baseline (Day 1) and Day 7. Lille null response was defined as having a Lille score ≥ 0.56.
Time frame: Day 7
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selonsertib + Prednisolone | Percentage of Participants With a Lille Null Response (Score ≥ 0.56) at Day 7 | 14.6 Percentage of participants |
| Placebo + Prednisolone | Percentage of Participants With a Lille Null Response (Score ≥ 0.56) at Day 7 | 7.8 Percentage of participants |
Secondary
Percentage of Participants With Estimated Mortality at Month 2 and Month 6: Combined Scoring Including Lille Score at Day 7 and Baseline Model for End-Stage Liver Disease (MELD) Score
The Lille score is a tool used to predict which participants with severe AH were not responding to corticosteroid therapy. It ranges between 0 and 1, with low scores (\< 0.16) indicating complete response or positive response to steroids (continue therapy) and high scores (≥ 0.56) indicating no response or poor response to steroids (stop therapy). MELD scores are used to assess prognosis and suitability for liver transplantation. Scores can range from 6 to 40, with higher scores indicating greater disease severity. A scoring system combining the Lille score at Day 7 and the baseline MELD score was used to calculate the percentage of participants expected to die by Month 2 and by Month 6.
Time frame: Baseline and Day 7 Time Points used to calculate Overall Mortality Risk at Months 2 and 6
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Selonsertib + Prednisolone | Percentage of Participants With Estimated Mortality at Month 2 and Month 6: Combined Scoring Including Lille Score at Day 7 and Baseline Model for End-Stage Liver Disease (MELD) Score | Mortality Risk at Month 2 | 13.0 Percentage of participants | Standard Deviation 10.94 |
| Selonsertib + Prednisolone | Percentage of Participants With Estimated Mortality at Month 2 and Month 6: Combined Scoring Including Lille Score at Day 7 and Baseline Model for End-Stage Liver Disease (MELD) Score | Mortality Risk at Month 6 | 19.8 Percentage of participants | Standard Deviation 15.15 |
| Placebo + Prednisolone | Percentage of Participants With Estimated Mortality at Month 2 and Month 6: Combined Scoring Including Lille Score at Day 7 and Baseline Model for End-Stage Liver Disease (MELD) Score | Mortality Risk at Month 2 | 9.7 Percentage of participants | Standard Deviation 6.57 |
| Placebo + Prednisolone | Percentage of Participants With Estimated Mortality at Month 2 and Month 6: Combined Scoring Including Lille Score at Day 7 and Baseline Model for End-Stage Liver Disease (MELD) Score | Mortality Risk at Month 6 | 15.2 Percentage of participants | Standard Deviation 9.28 |
Secondary
Percentage of Participants With Hepatorenal Syndrome (HRS)
The occurrence of HRS was confirmed based on the following diagnostic criteria from the International Ascites Club (IAC): 1) Cirrhosis with ascites, 2) Diagnosis of acute kidney injury (AKI) according to the ICA-AKI criteria, 3) Absence of shock, 4) No current or recent treatment with nephrotoxic drugs, and 5) Absence of parenchymal renal disease as indicated by proteinuria \>500 mg/day, microhematuria (\> 50 red blood cells per high power field) and/or abnormal renal ultrasonography.
Time frame: Up to 24 weeks
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selonsertib + Prednisolone | Percentage of Participants With Hepatorenal Syndrome (HRS) | 4.2 Percentage of participants |
| Placebo + Prednisolone | Percentage of Participants With Hepatorenal Syndrome (HRS) | 2.0 Percentage of participants |
Secondary
Percentage of Participants With Infection
The occurrence of bacterial, fungal, or viral infections was recorded. An infection was considered definite in participants with clinical evidence of infection and a positive culture from a normally sterile source (with the exception of spontaneous bacterial peritonitis).
Time frame: Up to 24 weeks
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selonsertib + Prednisolone | Percentage of Participants With Infection | 37.5 Percentage of participants |
| Placebo + Prednisolone | Percentage of Participants With Infection | 29.4 Percentage of participants |
Secondary
Percentage of Participants With Lille Response (Score < 0.45) at Day 7
The Lille score is a tool used to predict which participants with severe alcoholic hepatitis (AH) were not responding to corticosteroid therapy. It ranges between 0 and 1, with low scores (\< 0.16) indicating complete response or positive response to steroids (continue therapy) and high scores (≥ 0.56) indicating no response or poor response to steroids (stop therapy). The Lille score was calculated using baseline factors: age, albumin, total bilirubin, serum creatinine, prothrombin time; and the change in total bilirubin between baseline (Day 1) and Day 7. Lille response was defined as having a Lille score \< 0.45.
Time frame: Day 7
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selonsertib + Prednisolone | Percentage of Participants With Lille Response (Score < 0.45) at Day 7 | 77.1 Percentage of participants |
| Placebo + Prednisolone | Percentage of Participants With Lille Response (Score < 0.45) at Day 7 | 86.3 Percentage of participants |
p-value: 0.3Fisher Exact
Secondary
Percentage of Participants With Survival at Day 28 Using Kaplan-Meier
The percentage of participants with survival at Day 28 using Kaplan-Meier was calculated.
Time frame: Day 28
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selonsertib + Prednisolone | Percentage of Participants With Survival at Day 28 Using Kaplan-Meier | 95.7 Percentage of participants |
| Placebo + Prednisolone | Percentage of Participants With Survival at Day 28 Using Kaplan-Meier | 96.1 Percentage of participants |
Secondary
Percentage of Participants With Survival at Week 12 Using Kaplan-Meier
The percentage of participants with survival at Week 12 using Kaplan-Meier was calculated.
Time frame: Week 12
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selonsertib + Prednisolone | Percentage of Participants With Survival at Week 12 Using Kaplan-Meier | 75.3 Percentage of participants |
| Placebo + Prednisolone | Percentage of Participants With Survival at Week 12 Using Kaplan-Meier | 89.9 Percentage of participants |
Secondary
Percentage of Participants With Survival at Week 24 Using Kaplan-Meier
The percentage of participants with survival at Week 24 using Kaplan-Meier was calculated.
Time frame: Week 24
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selonsertib + Prednisolone | Percentage of Participants With Survival at Week 24 Using Kaplan-Meier | 70.3 Percentage of participants |
| Placebo + Prednisolone | Percentage of Participants With Survival at Week 24 Using Kaplan-Meier | 81.7 Percentage of participants |
Secondary
Percentage of Participants With Survival at Week 8 Using Kaplan-Meier
The percentage of participants with survival at Week 8 using Kaplan-Meier was calculated.
Time frame: Week 8
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selonsertib + Prednisolone | Percentage of Participants With Survival at Week 8 Using Kaplan-Meier | 80.0 Percentage of participants |
| Placebo + Prednisolone | Percentage of Participants With Survival at Week 8 Using Kaplan-Meier | 94.0 Percentage of participants |