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NCT02854631

Selonsertib in Combination With Prednisolone Versus Prednisolone Alone in Participants With Severe Alcoholic Hepatitis (AH)

Completed Phase 2 Results posted Last updated 6 February 2019
What this trial tests

Phase 2 trial testing Selonsertib in Alcoholic Hepatitis (AH) in 104 participants. Completed in 31 May 2018.

Timeline
1 September 2016
Primary endpoint
16 February 2018
31 May 2018

Quick facts

Lead sponsorGilead Sciences
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment104
Start date1 September 2016
Primary completion16 February 2018
Estimated completion31 May 2018
Sites44 locations across France, Belgium, Austria, United Kingdom, Canada, Switzerland, United States

Drugs / interventions tested

Conditions studied

Sponsor

Gilead Sciences — full company profile →

Who can join

Adults 18 to 70, any sex, with Alcoholic Hepatitis (AH). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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 Primary · 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 Co

TEAEs
GroupValue95% CI
Selonsertib + Prednisolone94.0
Placebo + Prednisolone94.2
TE SAEs
GroupValue95% CI
Selonsertib + Prednisolone50.0
Placebo + Prednisolone40.4
TEAEs (discontinuation of Selonsertib/Placebo)
GroupValue95% CI
Selonsertib + Prednisolone18.0
Placebo + Prednisolone7.7
TEAEs (discontinuation of Prednisolone)
GroupValue95% CI
Selonsertib + Prednisolone14.0
Placebo + Prednisolone11.5
TEAEs (discontinuation of both drugs in regimen)
GroupValue95% CI
Selonsertib + Prednisolone14.0
Placebo + Prednisolone7.7
Laboratory abnormalities (Grade 3 or 4)
GroupValue95% CI
Selonsertib + Prednisolone72.0
Placebo + Prednisolone72.0
Laboratory abnormalities (Grade 3)
GroupValue95% CI
Selonsertib + Prednisolone42.0
Placebo + Prednisolone52.0
Laboratory abnormalities (Grade 4)
GroupValue95% CI
Selonsertib + Prednisolone30.0
Placebo + Prednisolone20.0
Percentage of Participants Who Died by Day 28 Secondary · Day 28

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

GroupValue95% CI
Selonsertib + Prednisolone4.3
Placebo + Prednisolone4.0
Percentage of Participants Who Died by Week 8 Secondary · Week 8

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

GroupValue95% CI
Selonsertib + Prednisolone20.5
Placebo + Prednisolone6.1
Percentage of Participants Who Died by Week 12 Secondary · Week 12

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

GroupValue95% CI
Selonsertib + Prednisolone25.6
Placebo + Prednisolone10.2
Percentage of Participants Who Died by Week 24 Secondary · Week 24

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

GroupValue95% CI
Selonsertib + Prednisolone31.7
Placebo + Prednisolone18.8
Percentage of Participants With Survival at Day 28 Using Kaplan-Meier Secondary · Day 28

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

GroupValue95% CI
Selonsertib + Prednisolone95.784.0 – 98.9
Placebo + Prednisolone96.185.2 – 99.0
Percentage of Participants With Survival at Week 8 Using Kaplan-Meier Secondary · Week 8

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

GroupValue95% CI
Selonsertib + Prednisolone80.065.1 – 89.1
Placebo + Prednisolone94.082.6 – 98.0
Percentage of Participants With Survival at Week 12 Using Kaplan-Meier Secondary · Week 12

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

GroupValue95% CI
Selonsertib + Prednisolone75.359.8 – 85.5
Placebo + Prednisolone89.977.5 – 95.7
Percentage of Participants With Survival at Week 24 Using Kaplan-Meier Secondary · Week 24

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

GroupValue95% CI
Selonsertib + Prednisolone70.354.3 – 81.6
Placebo + Prednisolone81.767.7 – 90.0
Percentage of Participants Who Received a Liver Transplant Secondary · Day 28, Week 8, Week 12, and Week 24

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

Day 28
GroupValue95% CI
Selonsertib + Prednisolone2.2
Placebo + Prednisolone0
Week 8
GroupValue95% CI
Selonsertib + Prednisolone2.8
Placebo + Prednisolone0
Week 12
GroupValue95% CI
Selonsertib + Prednisolone3.0
Placebo + Prednisolone0
Week 24
GroupValue95% CI
Selonsertib + Prednisolone6.9
Placebo + Prednisolone2.6
Percentage of Participants With Hepatorenal Syndrome (HRS) Secondary · 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.

GroupValue95% CI
Selonsertib + Prednisolone4.2
Placebo + Prednisolone2.0
Percentage of Participants With Infection Secondary · 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).

GroupValue95% CI
Selonsertib + Prednisolone37.5
Placebo + Prednisolone29.4

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events: Up to Day 28 plus 30 days; All-Cause Mortality: Up to 24 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Selonsertib + Prednisolone
Serious: 25/50 (50%)
Deaths: 14/50
Placebo + Prednisolone
Serious: 21/52 (40%)
Deaths: 9/52

Serious adverse events (63 terms)

ReactionSystemSelonsertib + PrednisolonePlacebo + Prednisolone
Hepatic encephalopathyNervous system disorders
CoagulopathyBlood and lymphatic system disorders
CellulitisInfections and infestations
Oesophageal varices haemorrhageGastrointestinal disorders
Oedema peripheralGeneral disorders
Hepatorenal syndromeHepatobiliary disorders
Peritonitis bacterialInfections and infestations
PneumoniaInfections and infestations
HyponatraemiaMetabolism and nutrition disorders
Acute kidney injuryRenal and urinary disorders
HypotensionVascular disorders
Haemolytic anaemiaBlood and lymphatic system disorders
LeukocytosisBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
Abdominal pain lowerGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
AscitesGastrointestinal disorders
Gastric ulcer perforationGastrointestinal disorders
Gastrointestinal haemorrhageGastrointestinal disorders
HaematocheziaGastrointestinal disorders
Intestinal ischaemiaGastrointestinal disorders
PneumoperitoneumGastrointestinal disorders
Multiple organ dysfunction syndromeGeneral disorders
Alcoholic liver diseaseHepatobiliary disorders
Cholecystitis acuteHepatobiliary disorders
Other adverse events (33 terms — click to expand)

ReactionSystemSelonsertib + PrednisolonePlacebo + Prednisolone
AscitesGastrointestinal disorders
HyponatraemiaMetabolism and nutrition disorders
Oedema peripheralGeneral disorders
Hepatic encephalopathyNervous system disorders
PruritusSkin and subcutaneous tissue disorders
HypokalaemiaMetabolism and nutrition disorders
ConstipationGastrointestinal disorders
NauseaGastrointestinal disorders
FatigueGeneral disorders
OedemaGeneral disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
SepsisInfections and infestations
InsomniaPsychiatric disorders
Acute kidney injuryRenal and urinary disorders
RashSkin and subcutaneous tissue disorders
LeukocytosisBlood and lymphatic system disorders
Abdominal pain upperGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Varices oesophagealGastrointestinal disorders
VomitingGastrointestinal disorders
AstheniaGeneral disorders
PyrexiaGeneral disorders
HyperglycaemiaMetabolism and nutrition disorders
HyperkalaemiaMetabolism and nutrition disorders
HypomagnesaemiaMetabolism and nutrition disorders
HypophosphataemiaMetabolism and nutrition disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
HypotensionVascular disorders
Escherichia urinary tract infectionInfections and infestations
HeadacheNervous system disorders
AgitationPsychiatric disorders
CoughRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Hepatic encephalopathy, Coagulopathy, Cellulitis, Oesophageal varices haemorrhage, Oedema peripheral, Hepatorenal syndrome, Peritonitis bacterial, Pneumonia.

Data from ClinicalTrials.gov NCT02854631 adverse events section.

Sponsor's own description

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).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Alcohol-associated liver disease.
    Mackowiak B, Fu Y, Maccioni L, Gao B. · · 2024 · cited 204× · PMID 38299591 · DOI 10.1172/jci176345
  2. Recent Advances in Understanding of Pathogenesis of Alcohol-Associated Liver Disease.
    Wu X, Fan X, Miyata T, Kim A, et al · · 2023 · cited 167× · PMID 36270295 · DOI 10.1146/annurev-pathmechdis-031521-030435
  3. Recent advances in alcohol-related liver disease (ALD): summary of a Gut round table meeting.
    Avila MA, Dufour JF, Gerbes AL, Zoulim F, et al · · 2020 · cited 157× · PMID 31879281 · DOI 10.1136/gutjnl-2019-319720
  4. The knowns and unknowns of treatment for alcoholic hepatitis.
    Sehrawat TS, Liu M, Shah VH. · · 2020 · cited 76× · PMID 32277902 · DOI 10.1016/s2468-1253(19)30326-7
  5. Management of decompensated cirrhosis.
    Mansour D, McPherson S. · · 2018 · cited 74× · PMID 29700095 · DOI 10.7861/clinmedicine.18-2-s60
  6. Immunological mechanisms in steatotic liver diseases: An overview and clinical perspectives.
    Yan M, Man S, Ma L, Guo L, et al · · 2024 · cited 24× · PMID 38988278 · DOI 10.3350/cmh.2024.0315
  7. Alcohol-associated liver disease: Natural history, management and novel targeted therapies.
    Alvarado-Tapias E, Pose E, Gratacós-Ginès J, Clemente-Sánchez A, et al · · 2025 · cited 21× · PMID 39481875 · DOI 10.3350/cmh.2024.0709
  8. Alcohol-Related Liver Disease: An Overview on Pathophysiology, Diagnosis and Therapeutic Perspectives.
    Ha Y, Jeong I, Kim TH. · · 2022 · cited 19× · PMID 36289791 · DOI 10.3390/biomedicines10102530

Verify or expand the search:

Other trials of Selonsertib

Trials testing the same drug.

Other recruiting trials for Alcoholic Hepatitis (AH)

Currently open trials in the same condition.

Other Gilead Sciences trials

Trials by the same sponsor.

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Data sources for this page

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing