Trial Outcomes & Findings for Selonsertib in Combination With Prednisolone Versus Prednisolone Alone in Participants With Severe Alcoholic Hepatitis (AH) (NCT NCT02854631)

Last Updated: 2019-02-06

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

104 participants

Primary outcome timeframe

Up to Day 28 plus 30 days

Results posted on

2019-02-06

Participant Flow

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.

166 participants were screened.

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	52	52
Overall Study COMPLETED	26	37
Overall Study NOT COMPLETED	26	15

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Adverse Event	1	2
Overall Study Withdrew Consent	3	2
Overall Study Investigator's Discretion	2	0
Overall Study Death	12	8
Overall Study Liver Biopsy Inconsistent With Diagnosis	2	0
Overall Study Protocol Violation	0	1
Overall Study Subjects Randomized but Never Treated	2	0
Overall Study Lost to Follow-up	4	2

Baseline Characteristics

Only participants who were hospitalized were analyzed.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Selonsertib + Prednisolone n=50 Participants 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.	Placebo + Prednisolone n=52 Participants 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.	Total n=102 Participants Total of all reporting groups
Age, Continuous	49 Years STANDARD_DEVIATION 10.0 • n=50 Participants	49 Years STANDARD_DEVIATION 9.3 • n=52 Participants	49 Years STANDARD_DEVIATION 9.6 • n=102 Participants
Sex: Female, Male Female	21 Participants n=50 Participants	16 Participants n=52 Participants	37 Participants n=102 Participants
Sex: Female, Male Male	29 Participants n=50 Participants	36 Participants n=52 Participants	65 Participants n=102 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=50 Participants	1 Participants n=52 Participants	2 Participants n=102 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	46 Participants n=50 Participants	49 Participants n=52 Participants	95 Participants n=102 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=50 Participants	2 Participants n=52 Participants	5 Participants n=102 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=50 Participants	0 Participants n=52 Participants	0 Participants n=102 Participants
Race (NIH/OMB) Asian	2 Participants n=50 Participants	4 Participants n=52 Participants	6 Participants n=102 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=50 Participants	0 Participants n=52 Participants	0 Participants n=102 Participants
Race (NIH/OMB) Black or African American	0 Participants n=50 Participants	2 Participants n=52 Participants	2 Participants n=102 Participants
Race (NIH/OMB) White	44 Participants n=50 Participants	44 Participants n=52 Participants	88 Participants n=102 Participants
Race (NIH/OMB) More than one race	0 Participants n=50 Participants	0 Participants n=52 Participants	0 Participants n=102 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=50 Participants	2 Participants n=52 Participants	6 Participants n=102 Participants
Hospitalized at Time of Screening Yes	46 Participants n=50 Participants	48 Participants n=52 Participants	94 Participants n=102 Participants
Hospitalized at Time of Screening No	4 Participants n=50 Participants	4 Participants n=52 Participants	8 Participants n=102 Participants
Days Hospitalized Prior to First Dose Date	10 Days STANDARD_DEVIATION 4.6 • n=46 Participants • Only participants who were hospitalized were analyzed.	10 Days STANDARD_DEVIATION 5.2 • n=48 Participants • Only participants who were hospitalized were analyzed.	10 Days STANDARD_DEVIATION 4.9 • n=94 Participants • Only participants who were hospitalized were analyzed.
Baseline Infection Yes	6 Participants n=50 Participants	11 Participants n=52 Participants	17 Participants n=102 Participants
Baseline Infection No	44 Participants n=50 Participants	41 Participants n=52 Participants	85 Participants n=102 Participants
Alanine Aminotransferase (ALT)	45 Units per liter (U/L) STANDARD_DEVIATION 33.5 • n=49 Participants • Participants with available baseline values were analyzed.	48 Units per liter (U/L) STANDARD_DEVIATION 23.2 • n=52 Participants • Participants with available baseline values were analyzed.	46 Units per liter (U/L) STANDARD_DEVIATION 28.5 • n=101 Participants • Participants with available baseline values were analyzed.
Aspartate Aminotransferase (AST)	122 U/L STANDARD_DEVIATION 60.9 • n=49 Participants • Participants with available baseline values were analyzed.	129 U/L STANDARD_DEVIATION 59.9 • n=52 Participants • Participants with available baseline values were analyzed.	126 U/L STANDARD_DEVIATION 60.2 • n=101 Participants • Participants with available baseline values were analyzed.
Gamma Glutamyl Transferase (GGT)	238 U/L STANDARD_DEVIATION 175.5 • n=30 Participants • Participants with available baseline values were analyzed.	278 U/L STANDARD_DEVIATION 358.7 • n=33 Participants • Participants with available baseline values were analyzed.	259 U/L STANDARD_DEVIATION 285.0 • n=63 Participants • Participants with available baseline values were analyzed.
Alkaline Phosphatase	162 U/L STANDARD_DEVIATION 62.2 • n=49 Participants • Participants with available baseline values were analyzed.	189 U/L STANDARD_DEVIATION 111.3 • n=52 Participants • Participants with available baseline values were analyzed.	176 U/L STANDARD_DEVIATION 91.4 • n=101 Participants • Participants with available baseline values were analyzed.
Bilirubin	14.3 Milligrams per deciliter (mg/dL) STANDARD_DEVIATION 8.35 • n=49 Participants • Participants with available baseline values were analyzed.	14.5 Milligrams per deciliter (mg/dL) STANDARD_DEVIATION 7.78 • n=52 Participants • Participants with available baseline values were analyzed.	14.4 Milligrams per deciliter (mg/dL) STANDARD_DEVIATION 8.02 • n=101 Participants • Participants with available baseline values were analyzed.
Albumin	3.1 Grams per deciltre (g/dL) STANDARD_DEVIATION 0.62 • n=49 Participants • Participants with available baseline values were analyzed.	3.0 Grams per deciltre (g/dL) STANDARD_DEVIATION 0.53 • n=52 Participants • Participants with available baseline values were analyzed.	3.0 Grams per deciltre (g/dL) STANDARD_DEVIATION 0.58 • n=101 Participants • Participants with available baseline values were analyzed.
International Normalized Ratio (INR)	1.7 Ratio STANDARD_DEVIATION 0.31 • n=47 Participants • Participants with available baseline values were analyzed.	1.6 Ratio STANDARD_DEVIATION 0.22 • n=52 Participants • Participants with available baseline values were analyzed.	1.6 Ratio STANDARD_DEVIATION 0.27 • n=99 Participants • Participants with available baseline values were analyzed.
Model for End-Stage Liver Disease (MELD) Score	22 Units on a scale STANDARD_DEVIATION 4.2 • n=50 Participants	22 Units on a scale STANDARD_DEVIATION 4.4 • n=52 Participants	22 Units on a scale STANDARD_DEVIATION 4.3 • n=102 Participants
Child-Pugh-Turcotte (CPT) Score	10 Units on a scale STANDARD_DEVIATION 1.2 • n=47 Participants • Participants with available baseline values were analyzed.	10 Units on a scale STANDARD_DEVIATION 1.3 • n=52 Participants • Participants with available baseline values were analyzed.	10 Units on a scale STANDARD_DEVIATION 1.2 • n=99 Participants • Participants with available baseline values were analyzed.
Maddrey Discriminant Function (DF) Score	42 Units on a scale STANDARD_DEVIATION 16.9 • n=44 Participants • Participants with available baseline values were analyzed.	38 Units on a scale STANDARD_DEVIATION 11.4 • n=52 Participants • Participants with available baseline values were analyzed.	40 Units on a scale STANDARD_DEVIATION 14.2 • n=96 Participants • Participants with available baseline values were analyzed.

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Selonsertib + Prednisolone n=50 Participants 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.	Placebo + Prednisolone n=52 Participants 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.
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	94.2 Percentage of participants
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	40.4 Percentage of participants
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	7.7 Percentage of participants
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	11.5 Percentage of participants
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	7.7 Percentage of participants
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	72.0 Percentage of participants
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	52.0 Percentage of participants
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	20.0 Percentage of participants

SECONDARY outcome

Timeframe: 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.

The percentage of participants who died by Day 28 was calculated.

Outcome measures

Outcome measures
Measure	Selonsertib + Prednisolone n=47 Participants 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.	Placebo + Prednisolone n=50 Participants 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.
Percentage of Participants Who Died by Day 28	4.3 Percentage of participants	4.0 Percentage of participants

SECONDARY outcome

Timeframe: Week 8

Population: Participants in the Full Analysis Set with available data were analyzed.

The percentage of participants who died by Week 8 was calculated.

Outcome measures

Outcome measures
Measure	Selonsertib + Prednisolone n=44 Participants 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.	Placebo + Prednisolone n=49 Participants 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.
Percentage of Participants Who Died by Week 8	20.5 Percentage of participants	6.1 Percentage of participants

SECONDARY outcome

Timeframe: Week 12

Population: Participants in the Full Analysis Set with available data were analyzed.

The percentage of participants who died by Week 12 was calculated.

Outcome measures

Outcome measures
Measure	Selonsertib + Prednisolone n=43 Participants 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.	Placebo + Prednisolone n=49 Participants 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.
Percentage of Participants Who Died by Week 12	25.6 Percentage of participants	10.2 Percentage of participants

SECONDARY outcome

Timeframe: Week 24

Population: Participants in the Full Analysis Set with available data were analyzed.

The percentage of participants who died by Week 24 was calculated.

Outcome measures

Outcome measures
Measure	Selonsertib + Prednisolone n=41 Participants 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.	Placebo + Prednisolone n=48 Participants 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.
Percentage of Participants Who Died by Week 24	31.7 Percentage of participants	18.8 Percentage of participants

SECONDARY outcome

Timeframe: Day 28

Population: Full Analysis Set

The percentage of participants with survival at Day 28 using Kaplan-Meier was calculated.

Outcome measures

Outcome measures
Measure	Selonsertib + Prednisolone n=48 Participants 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.	Placebo + Prednisolone n=51 Participants 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.
Percentage of Participants With Survival at Day 28 Using Kaplan-Meier	95.7 Percentage of participants Interval 84.0 to 98.9	96.1 Percentage of participants Interval 85.2 to 99.0

SECONDARY outcome

Timeframe: Week 8

Population: Full Analysis Set

The percentage of participants with survival at Week 8 using Kaplan-Meier was calculated.

Outcome measures

Outcome measures
Measure	Selonsertib + Prednisolone n=48 Participants 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.	Placebo + Prednisolone n=51 Participants 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.
Percentage of Participants With Survival at Week 8 Using Kaplan-Meier	80.0 Percentage of participants Interval 65.1 to 89.1	94.0 Percentage of participants Interval 82.6 to 98.0

SECONDARY outcome

Timeframe: Week 12

Population: Full Analysis Set

The percentage of participants with survival at Week 12 using Kaplan-Meier was calculated.

Outcome measures

Outcome measures
Measure	Selonsertib + Prednisolone n=48 Participants 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.	Placebo + Prednisolone n=51 Participants 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.
Percentage of Participants With Survival at Week 12 Using Kaplan-Meier	75.3 Percentage of participants Interval 59.8 to 85.5	89.9 Percentage of participants Interval 77.5 to 95.7

SECONDARY outcome

Timeframe: Week 24

Population: Full Analysis Set

The percentage of participants with survival at Week 24 using Kaplan-Meier was calculated.

Outcome measures

Outcome measures
Measure	Selonsertib + Prednisolone n=48 Participants 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.	Placebo + Prednisolone n=51 Participants 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.
Percentage of Participants With Survival at Week 24 Using Kaplan-Meier	70.3 Percentage of participants Interval 54.3 to 81.6	81.7 Percentage of participants Interval 67.7 to 90.0

SECONDARY outcome

Timeframe: Day 28, Week 8, Week 12, and Week 24

Population: Participants in the Full Analysis Set with available data were analyzed.

The percentage of participants who received a liver transplant by week 24 was calculated.

Outcome measures

Outcome measures
Measure	Selonsertib + Prednisolone n=45 Participants 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.	Placebo + Prednisolone n=48 Participants 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.
Percentage of Participants Who Received a Liver Transplant Day 28	2.2 Percentage of participants	0 Percentage of participants
Percentage of Participants Who Received a Liver Transplant Week 8	2.8 Percentage of participants	0 Percentage of participants
Percentage of Participants Who Received a Liver Transplant Week 12	3.0 Percentage of participants	0 Percentage of participants
Percentage of Participants Who Received a Liver Transplant Week 24	6.9 Percentage of participants	2.6 Percentage of participants

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Full Analysis Set

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.

Outcome measures

Outcome measures
Measure	Selonsertib + Prednisolone n=48 Participants 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.	Placebo + Prednisolone n=51 Participants 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.
Percentage of Participants With Hepatorenal Syndrome (HRS)	4.2 Percentage of participants	2.0 Percentage of participants

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Full Analysis Set

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).

Outcome measures

Outcome measures
Measure	Selonsertib + Prednisolone n=48 Participants 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.	Placebo + Prednisolone n=51 Participants 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.
Percentage of Participants With Infection	37.5 Percentage of participants	29.4 Percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Selonsertib + Prednisolone n=41 Participants 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.	Placebo + Prednisolone n=45 Participants 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.
Length of Hospital Stay Released from initial hospitalization	11.0 Days Standard Deviation 11.53	11.0 Days Standard Deviation 11.25
Length of Hospital Stay Died during initial hospitalization	36.0 Days Standard Deviation 18.52	6.0 Days Standard Deviation 1.41

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to 24 weeks

Population: Participants in the Full Analysis Set with available baseline and any postbaseline data were analyzed.

Change from Baseline was calculated as the value at endpoint minus the value at Baseline.

Outcome measures

Outcome measures
Measure	Selonsertib + Prednisolone n=47 Participants 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.	Placebo + Prednisolone n=49 Participants 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.
Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT) Change at Week 1	26 U/L Standard Deviation 40.7	29 U/L Standard Deviation 28.2
Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT) Change at Week 2	31 U/L Standard Deviation 35.0	36 U/L Standard Deviation 33.6
Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT) Change at Week 3	24 U/L Standard Deviation 32.6	24 U/L Standard Deviation 28.8
Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT) Change at Week 4	15 U/L Standard Deviation 28.7	12 U/L Standard Deviation 32.6
Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT) Change at Week 6	-10 U/L Standard Deviation 19.9	-18 U/L Standard Deviation 21.8
Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT) Change at Week 8	-13 U/L Standard Deviation 18.1	-20 U/L Standard Deviation 24.6
Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT) Change at Week 12	-15 U/L Standard Deviation 19.3	-17 U/L Standard Deviation 42.9
Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT) Change at Week 16	-14 U/L Standard Deviation 21.0	-21 U/L Standard Deviation 28.6
Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT) Change at Week 20	-12 U/L Standard Deviation 18.6	-24 U/L Standard Deviation 21.7
Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT) Change at Week 24	-12 U/L Standard Deviation 19.4	-22 U/L Standard Deviation 21.8

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to 24 weeks

Population: Participants in the Full Analysis Set with available baseline and any postbaseline data were analyzed.

Change from Baseline was calculated as the value at endpoint minus the value at Baseline.

Outcome measures

Outcome measures
Measure	Selonsertib + Prednisolone n=47 Participants 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.	Placebo + Prednisolone n=49 Participants 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.
Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST) Change at Week 1	-2 U/L Standard Deviation 66.9	4 U/L Standard Deviation 52.8
Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST) Change at Week 2	-17 U/L Standard Deviation 58.5	-11 U/L Standard Deviation 52.9
Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST) Change at Week 3	-34 U/L Standard Deviation 38.4	-39 U/L Standard Deviation 54.0
Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST) Change at Week 4	-45 U/L Standard Deviation 35.8	-55 U/L Standard Deviation 60.2
Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST) Change at Week 6	-54 U/L Standard Deviation 45.6	-74 U/L Standard Deviation 60.0
Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST) Change at Week 8	-48 U/L Standard Deviation 46.6	-61 U/L Standard Deviation 63.5
Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST) Change at Week 12	-59 U/L Standard Deviation 45.2	-63 U/L Standard Deviation 86.5
Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST) Change at Week 16	-59 U/L Standard Deviation 56.9	-70 U/L Standard Deviation 76.4
Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST) Change at Week 20	-57 U/L Standard Deviation 46.9	-64 U/L Standard Deviation 72.6
Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST) Change at Week 24	-59 U/L Standard Deviation 49.6	-68 U/L Standard Deviation 59.4

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to 24 weeks

Population: Participants in the Full Analysis Set with available baseline and any postbaseline data were analyzed.

Change from Baseline was calculated as the value at endpoint minus the value at Baseline.

Outcome measures

Outcome measures
Measure	Selonsertib + Prednisolone n=29 Participants 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.	Placebo + Prednisolone n=33 Participants 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.
Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT) Change at Week 1	3 U/L Standard Deviation 79.2	-1 U/L Standard Deviation 192.5
Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT) Change at Week 2	9 U/L Standard Deviation 140.8	9 U/L Standard Deviation 189.0
Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT) Change at Week 3	-12 U/L Standard Deviation 170.2	9 U/L Standard Deviation 197.1
Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT) Change at Week 4	-7 U/L Standard Deviation 169.3	-5 U/L Standard Deviation 284.0
Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT) Change at Week 6	-61 U/L Standard Deviation 139.7	-72 U/L Standard Deviation 173.4
Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT) Change at Week 8	-96 U/L Standard Deviation 137.7	-121 U/L Standard Deviation 314.2
Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT) Change at Week 12	-105 U/L Standard Deviation 136.1	-100 U/L Standard Deviation 274.0
Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT) Change at Week 16	-87 U/L Standard Deviation 157.4	-114 U/L Standard Deviation 251.3
Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT) Change at Week 20	-134 U/L Standard Deviation 150.9	-85 U/L Standard Deviation 342.9
Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT) Change at Week 24	-131 U/L Standard Deviation 154.4	-54 U/L Standard Deviation 277.0

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to 24 weeks

Population: Participants in the Full Analysis Set with available baseline and any postbaseline data were analyzed.

Change from Baseline was calculated as the value at endpoint minus the value at Baseline.

Outcome measures

Outcome measures
Measure	Selonsertib + Prednisolone n=47 Participants 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.	Placebo + Prednisolone n=49 Participants 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.
Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase Change at Week 1	11 U/L Standard Deviation 55.3	-3 U/L Standard Deviation 63.6
Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase Change at Week 2	23 U/L Standard Deviation 70.7	-5 U/L Standard Deviation 70.6
Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase Change at Week 3	10 U/L Standard Deviation 68.7	-4 U/L Standard Deviation 89.8
Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase Change at Week 4	8 U/L Standard Deviation 71.7	-16 U/L Standard Deviation 89.8
Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase Change at Week 6	1 U/L Standard Deviation 65.3	-21 U/L Standard Deviation 69.8
Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase Change at Week 8	-14 U/L Standard Deviation 52.6	-47 U/L Standard Deviation 97.8
Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase Change at Week 12	-35 U/L Standard Deviation 65.0	-52 U/L Standard Deviation 102.8
Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase Change at Week 16	-26 U/L Standard Deviation 83.1	-50 U/L Standard Deviation 92.8
Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase Change at Week 20	-29 U/L Standard Deviation 83.3	-45 U/L Standard Deviation 106.8
Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase Change at Week 24	-25 U/L Standard Deviation 87.3	-43 U/L Standard Deviation 101.0

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to 24 weeks

Population: Participants in the Full Analysis Set with available baseline and any postbaseline data were analyzed.

Change from Baseline was calculated as the value at endpoint minus the value at Baseline.

Outcome measures

Outcome measures
Measure	Selonsertib + Prednisolone n=47 Participants 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.	Placebo + Prednisolone n=49 Participants 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.
Change From Baseline in Liver Biochemistry Tests: Bilirubin Change at Week 1	-2.1 mg/dL Standard Deviation 3.99	-4.3 mg/dL Standard Deviation 3.46
Change From Baseline in Liver Biochemistry Tests: Bilirubin Change at Week 2	-2.9 mg/dL Standard Deviation 5.34	-6.3 mg/dL Standard Deviation 4.99
Change From Baseline in Liver Biochemistry Tests: Bilirubin Change at Week 3	-4.8 mg/dL Standard Deviation 7.68	-7.2 mg/dL Standard Deviation 6.21
Change From Baseline in Liver Biochemistry Tests: Bilirubin Change at Week 4	-6.3 mg/dL Standard Deviation 6.01	-8.6 mg/dL Standard Deviation 6.52
Change From Baseline in Liver Biochemistry Tests: Bilirubin Change at Week 6	-8.7 mg/dL Standard Deviation 8.22	-9.3 mg/dL Standard Deviation 7.40
Change From Baseline in Liver Biochemistry Tests: Bilirubin Change at Week 8	-8.4 mg/dL Standard Deviation 7.53	-10.3 mg/dL Standard Deviation 7.36
Change From Baseline in Liver Biochemistry Tests: Bilirubin Change at Week 12	-9.5 mg/dL Standard Deviation 7.86	-11.2 mg/dL Standard Deviation 7.79
Change From Baseline in Liver Biochemistry Tests: Bilirubin Change at Week 16	-9.4 mg/dL Standard Deviation 8.35	-11.3 mg/dL Standard Deviation 8.37
Change From Baseline in Liver Biochemistry Tests: Bilirubin Change at Week 20	-8.1 mg/dL Standard Deviation 9.88	-11.3 mg/dL Standard Deviation 7.94
Change From Baseline in Liver Biochemistry Tests: Bilirubin Change at Week 24	-9.4 mg/dL Standard Deviation 7.72	-10.7 mg/dL Standard Deviation 8.09

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to 24 weeks

Population: Participants in the Full Analysis Set with available baseline and any postbaseline data were analyzed.

Change from Baseline was calculated as the value at endpoint minus the value at Baseline.

Outcome measures

Outcome measures
Measure	Selonsertib + Prednisolone n=47 Participants 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.	Placebo + Prednisolone n=49 Participants 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.
Change From Baseline in Liver Biochemistry Tests: Albumin Change at Week 1	0.2 g/dL Standard Deviation 0.45	0.2 g/dL Standard Deviation 0.31
Change From Baseline in Liver Biochemistry Tests: Albumin Change at Week 2	0.3 g/dL Standard Deviation 0.47	0.4 g/dL Standard Deviation 0.45
Change From Baseline in Liver Biochemistry Tests: Albumin Change at Week 3	0.3 g/dL Standard Deviation 0.58	0.4 g/dL Standard Deviation 0.54
Change From Baseline in Liver Biochemistry Tests: Albumin Change at Week 4	0.4 g/dL Standard Deviation 0.63	0.5 g/dL Standard Deviation 0.57
Change From Baseline in Liver Biochemistry Tests: Albumin Change at Week 6	0.2 g/dL Standard Deviation 0.82	0.4 g/dL Standard Deviation 0.67
Change From Baseline in Liver Biochemistry Tests: Albumin Change at Week 8	0.3 g/dL Standard Deviation 0.80	0.6 g/dL Standard Deviation 0.66
Change From Baseline in Liver Biochemistry Tests: Albumin Change at Week 12	0.5 g/dL Standard Deviation 0.82	0.6 g/dL Standard Deviation 0.68
Change From Baseline in Liver Biochemistry Tests: Albumin Change at Week 16	0.5 g/dL Standard Deviation 0.95	0.7 g/dL Standard Deviation 0.64
Change From Baseline in Liver Biochemistry Tests: Albumin Change at Week 20	0.8 g/dL Standard Deviation 0.92	0.8 g/dL Standard Deviation 0.68
Change From Baseline in Liver Biochemistry Tests: Albumin Change at Week 24	0.8 g/dL Standard Deviation 0.76	0.8 g/dL Standard Deviation 0.68

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to 24 weeks

Population: Participants in the Full Analysis Set with available baseline and any postbaseline data were analyzed.

Change from Baseline was calculated as the value at endpoint minus the value at Baseline.

Outcome measures

Outcome measures
Measure	Selonsertib + Prednisolone n=45 Participants 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.	Placebo + Prednisolone n=49 Participants 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.
Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR) Change at Week 1	-0.1 Ratio Standard Deviation 0.28	-0.1 Ratio Standard Deviation 0.16
Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR) Change at Week 2	-0.2 Ratio Standard Deviation 0.32	-0.2 Ratio Standard Deviation 0.23
Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR) Change at Week 3	-0.3 Ratio Standard Deviation 0.38	-0.2 Ratio Standard Deviation 0.25
Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR) Change at Week 4	-0.3 Ratio Standard Deviation 0.36	-0.2 Ratio Standard Deviation 0.18
Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR) Change at Week 6	-0.2 Ratio Standard Deviation 0.40	-0.2 Ratio Standard Deviation 0.33
Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR) Change at Week 8	-0.3 Ratio Standard Deviation 0.43	-0.3 Ratio Standard Deviation 0.19
Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR) Change at Week 12	-0.3 Ratio Standard Deviation 0.41	-0.3 Ratio Standard Deviation 0.19
Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR) Change at Week 16	-0.3 Ratio Standard Deviation 0.40	-0.3 Ratio Standard Deviation 0.22
Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR) Change at Week 20	-0.3 Ratio Standard Deviation 0.42	-0.3 Ratio Standard Deviation 0.27
Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR) Change at Week 24	-0.4 Ratio Standard Deviation 0.36	-0.3 Ratio Standard Deviation 0.32

SECONDARY outcome

Timeframe: Day 7

Population: Full Analysis Set

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.

Outcome measures

Outcome measures
Measure	Selonsertib + Prednisolone n=48 Participants 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.	Placebo + Prednisolone n=51 Participants 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.
Percentage of Participants With Lille Response (Score < 0.45) at Day 7	77.1 Percentage of participants	86.3 Percentage of participants

SECONDARY outcome

Timeframe: Day 7

Population: Full Analysis Set

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.

Outcome measures

Outcome measures
Measure	Selonsertib + Prednisolone n=48 Participants 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.	Placebo + Prednisolone n=51 Participants 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.
Percentage of Participants With a Lille Null Response (Score ≥ 0.56) at Day 7	14.6 Percentage of participants	7.8 Percentage of participants

SECONDARY outcome

Timeframe: Day 7

Population: Participants in the Full Analysis Set with available data were analyzed.

Outcome measures

Outcome measures
Measure	Selonsertib + Prednisolone n=47 Participants 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.	Placebo + Prednisolone n=48 Participants 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.
Lille Score at Day 7 as a Continuous Variable	0.254 Lille score Standard Deviation 0.2495	0.178 Lille score Standard Deviation 0.1534

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Selonsertib + Prednisolone n=47 Participants 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.	Placebo + Prednisolone n=48 Participants 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.
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	9.7 Percentage of participants Standard Deviation 6.57
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	15.2 Percentage of participants Standard Deviation 9.28

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to 24 weeks

Population: Participants in the Full Analysis Set with available baseline and any postbaseline data were analyzed.

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.

Outcome measures

Outcome measures
Measure	Selonsertib + Prednisolone n=48 Participants 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.	Placebo + Prednisolone n=49 Participants 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.
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	-7 Units on a scale Standard Deviation 5.2
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	-8 Units on a scale Standard Deviation 4.7
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 6.0	-10 Units on a scale Standard Deviation 4.8
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	-9 Units on a scale Standard Deviation 5.5
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	-10 Units on a scale Standard Deviation 5.4
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	-10 Units on a scale Standard Deviation 5.6
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	-3 Units on a scale Standard Deviation 2.6
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 4.0	-5 Units on a scale Standard Deviation 3.5
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	-5 Units on a scale Standard Deviation 3.9
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	-6 Units on a scale Standard Deviation 3.9

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to 24 weeks

Population: Participants in the Full Analysis Set with available baseline and any postbaseline data were analyzed.

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

Outcome measures

Outcome measures
Measure	Selonsertib + Prednisolone n=45 Participants 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.	Placebo + Prednisolone n=49 Participants 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.
Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score Change at Week 1	0 Units on a scale Standard Deviation 1.5	-1 Units on a scale Standard Deviation 0.9
Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score Change at Week 2	-1 Units on a scale Standard Deviation 1.4	-1 Units on a scale Standard Deviation 1.4
Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score Change at Week 3	-1 Units on a scale Standard Deviation 1.7	-1 Units on a scale Standard Deviation 1.4
Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score Change at Week 4	-1 Units on a scale Standard Deviation 1.9	-2 Units on a scale Standard Deviation 1.7
Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score Change at Week 6	-1 Units on a scale Standard Deviation 2.1	-2 Units on a scale Standard Deviation 1.7
Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score Change at Week 8	-2 Units on a scale Standard Deviation 2.4	-2 Units on a scale Standard Deviation 1.5
Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score Change at Week 12	-2 Units on a scale Standard Deviation 2.2	-3 Units on a scale Standard Deviation 1.7
Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score Change at Week 16	-2 Units on a scale Standard Deviation 2.4	-3 Units on a scale Standard Deviation 1.8
Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score Change at Week 20	-3 Units on a scale Standard Deviation 2.3	-3 Units on a scale Standard Deviation 1.6
Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score Change at Week 24	-3 Units on a scale Standard Deviation 1.7	-3 Units on a scale Standard Deviation 1.6

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to 24 weeks

Population: Participants in the Full Analysis Set with available baseline and any postbaseline data were analyzed.

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.

Outcome measures

Outcome measures
Measure	Selonsertib + Prednisolone n=42 Participants 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.	Placebo + Prednisolone n=49 Participants 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.
Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score Change at Week 4	-19 Units on a scale Standard Deviation 20.0	-19 Units on a scale Standard Deviation 10.9
Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score Change at Week 12	-23 Units on a scale Standard Deviation 21.8	-23 Units on a scale Standard Deviation 12.2
Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score Change at Week 16	-23 Units on a scale Standard Deviation 22.6	-23 Units on a scale Standard Deviation 13.7
Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score Change at Week 1	-8 Units on a scale Standard Deviation 15.2	-10 Units on a scale Standard Deviation 7.7
Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score Change at Week 2	-13 Units on a scale Standard Deviation 18.1	-15 Units on a scale Standard Deviation 11.4
Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score Change at Week 3	-17 Units on a scale Standard Deviation 21.8	-17 Units on a scale Standard Deviation 13.3
Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score Change at Week 6	-20 Units on a scale Standard Deviation 23.2	-19 Units on a scale Standard Deviation 17.6
Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score Change at Week 8	-19 Units on a scale Standard Deviation 21.5	-21 Units on a scale Standard Deviation 12.0
Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score Change at Week 20	-25 Units on a scale Standard Deviation 26.2	-23 Units on a scale Standard Deviation 15.4
Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score Change at Week 24	-27 Units on a scale Standard Deviation 21.7	-22 Units on a scale Standard Deviation 16.9

Adverse Events

Selonsertib + Prednisolone

Serious events: 25 serious events

Other events: 43 other events

Deaths: 14 deaths

Placebo + Prednisolone

Serious events: 21 serious events

Other events: 42 other events

Deaths: 9 deaths

Serious adverse events

Other adverse events

Additional Information

Gilead Clinical Study Information Center

Gilead Sciences

Phone: 1-833-445-3230 (GILEAD-0)

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
Publication restrictions are in place

Restriction type: OTHER

Measure	Selonsertib + Prednisolone n=50 participants at risk 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.	Placebo + Prednisolone n=52 participants at risk 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.
Blood and lymphatic system disorders Leukocytosis	8.0% 4/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	3.8% 2/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
Gastrointestinal disorders Abdominal pain upper	8.0% 4/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	1.9% 1/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
Gastrointestinal disorders Ascites	30.0% 15/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	26.9% 14/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
Gastrointestinal disorders Constipation	12.0% 6/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	9.6% 5/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
Gastrointestinal disorders Diarrhoea	8.0% 4/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	7.7% 4/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
Gastrointestinal disorders Nausea	12.0% 6/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	3.8% 2/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
Gastrointestinal disorders Varices oesophageal	6.0% 3/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	7.7% 4/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
Gastrointestinal disorders Vomiting	8.0% 4/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	1.9% 1/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
General disorders Asthenia	8.0% 4/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	3.8% 2/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
General disorders Fatigue	8.0% 4/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	11.5% 6/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
General disorders Oedema	8.0% 4/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	11.5% 6/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
General disorders Oedema peripheral	24.0% 12/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	21.2% 11/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
General disorders Pyrexia	2.0% 1/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	7.7% 4/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
Infections and infestations Escherichia urinary tract infection	6.0% 3/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	1.9% 1/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
Infections and infestations Sepsis	10.0% 5/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	0.00% 0/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
Metabolism and nutrition disorders Hyperglycaemia	8.0% 4/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	7.7% 4/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
Metabolism and nutrition disorders Hyperkalaemia	2.0% 1/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	7.7% 4/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
Metabolism and nutrition disorders Hypokalaemia	14.0% 7/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	7.7% 4/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
Metabolism and nutrition disorders Hypomagnesaemia	8.0% 4/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	5.8% 3/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
Metabolism and nutrition disorders Hyponatraemia	30.0% 15/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	1.9% 1/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
Metabolism and nutrition disorders Hypophosphataemia	8.0% 4/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	1.9% 1/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Muscle spasms	6.0% 3/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	7.7% 4/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
Nervous system disorders Headache	2.0% 1/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	5.8% 3/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
Nervous system disorders Hepatic encephalopathy	24.0% 12/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	13.5% 7/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
Psychiatric disorders Agitation	0.00% 0/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	5.8% 3/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
Psychiatric disorders Insomnia	10.0% 5/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	9.6% 5/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
Renal and urinary disorders Acute kidney injury	10.0% 5/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	1.9% 1/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	4.0% 2/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	5.8% 3/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.0% 3/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	11.5% 6/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Epistaxis	8.0% 4/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	3.8% 2/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Pruritus	16.0% 8/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	7.7% 4/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Rash	4.0% 2/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	9.6% 5/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
Vascular disorders Hypotension	8.0% 4/50 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.	5.8% 3/52 • Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks Safety Analysis Set included all participants who were randomized and took at least 1 dose of study drug.