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Study to Evaluate the Safety and Efficacy of Selonsertib, Firsocostat, Cilofexor, and Combinations in Participants With Bridging Fibrosis or Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis (NASH)

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Selonsertib, GS-0976, GS-9674, and Combinations in Subjects With Bridging (F3) Fibrosis or Compensated Cirrhosis (F4) Due to Nonalcoholic Steatohepatitis (NASH)

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03449446
Acronym
ATLAS
Enrollment
395
Registered
2018-02-28
Start date
2018-03-21
Completion date
2019-11-19
Last updated
2020-12-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Nonalcoholic Steatohepatitis

Brief summary

The primary objectives of this study are: * To assess the safety and tolerability of selonsertib (SEL), firsocostat (FIR) and cilofexor (CILO), administered alone or in combination, in participants with bridging fibrosis or compensated cirrhosis due to NASH * To evaluate changes in liver fibrosis, without worsening of NASH

Interventions

DRUGSEL

18 mg tablet administered orally once daily without regard to food

DRUGFIR

20 mg tablet administered orally once daily without regard to food

DRUGCILO

30 mg tablet administered orally once daily without regard to food

DRUGPlacebo to match FIR

Tablet administered orally once daily without regard to food

DRUGPlacebo to match CILO

Tablet administered orally once daily without regard to food

DRUGPlacebo to match SEL

Tablet administered orally once daily without regard to food

Sponsors

Gilead Sciences
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No

Inclusion criteria

Key Inclusion Criteria: * Liver biopsy consistent with NASH and F3 or F4 in the opinion of the central reader * In participants who have never had a liver biopsy, liver stiffness by FibroScan® ≥ 14.0 kPa and Enhanced Liver Fibrosis (ELF™) Test score ≥ 9.8 at Screening * Screening laboratory parameters, as determined by the central laboratory: * Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min, as calculated by the Cockcroft-Gault equation * Hemoglobin A1c (HbA1c) ≤ 9.5% * Alanine aminotransferase (ALT) \< 5 x Upper Limits of Normal (ULN) * Platelet count ≥ 125,000/μL Key

Exclusion criteria

* Prior history of decompensated liver disease including ascites, hepatic encephalopathy, or variceal bleeding * Child-Pugh (CP) score \> 6 at Screening, unless due to an alternative etiology such as Gilbert's syndrome or therapeutic anticoagulation * Model for End-Stage Liver Disease (MELD) score \> 12 at Screening, unless due to an alternate etiology such as therapeutic anticoagulation * Other causes of liver disease based on medical history and/or centralized review of liver histology, including but not limited to: alcoholic liver disease, hepatitis B, hepatitis C, autoimmune disorders (eg, primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis), drug-induced hepatotoxicity, Wilson disease, clinically significant iron overload, or alpha-1-antitrypsin deficiency requiring treatment * History of liver transplantation * Current or prior history of hepatocellular carcinoma Note: Other protocol defined Inclusion/

Design outcomes

Primary

MeasureTime frameDescription
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)First dose date up to 48 weeks plus 30 days—
Percentage of Participants Experiencing Treatment-Emergent Laboratory AbnormalitiesFirst dose date up to 48 weeks plus 30 daysTreatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. Participants with any laboratory abnormality were reported.
Percentage of Participants Who Achieved a ≥ 1-Stage Improvement in Fibrosis Without Worsening of NASH at Week 48Week 48Fibrosis improvement was defined as ≥ 1-stage decrease from baseline in fibrosis according to the NASH clinical research network classification (CRN) classification. Worsening of NASH was defined as ≥ 1-point increase from baseline in hepatocellular ballooning or lobular inflammation. The 95% CI was based on the Clopper-Pearson method.

Countries

Australia, Canada, Hong Kong, New Zealand, Puerto Rico, United States

Participant flow

Recruitment details

Participants were enrolled at study sites in United States, Australia, Canada, Hong King and New Zealand. The first participant was screened on 21 Mar 2018. The last study visit occurred on 19 Nov 2019.

Pre-assignment details

950 participants were screened.

Participants by arm

ArmCount
Selonsertib
Participants received SEL 18 mg tablet + placebo to match FIR 20 mg tablet + placebo to match CILO 30 mg tablet orally once daily for 48 weeks.
39
Firsocostat
Participants received placebo to match SEL 18 mg tablet + FIR 20 mg tablet + placebo to match CILO 30 mg tablet orally once daily for 48 weeks.
40
Cilofexor
Participants received placebo to match SEL 18 mg + placebo to match FIR 20 mg tablet + CILO 30 mg tablet orally once daily for 48 weeks.
40
SEL + FIR
Participants received SEL 18 mg tablet + FIR 20 mg tablet + placebo to match CILO 30 mg tablet orally once daily for 48 weeks.
79
SEL + CILO
Participants received SEL 18 mg tablet + placebo to match FIR 20 mg tablet + CILO 30 mg tablet orally once daily for 48 weeks.
77
FIR + CILO
Participants received placebo to match SEL 18 mg tablet + FIR 20 mg tablet + CILO 30 mg tablet orally once daily for 48 weeks.
78
Placebo
Participants received placebo to match SEL 18 mg tablet + placebo to match FIR 20 mg tablet + placebo to match CILO 30 mg tablet orally once daily for 48 weeks.
39
Total392

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003FG004FG005FG006
Overall StudyAdverse Event1210020
Overall StudyDeath0000100
Overall StudyInvestigator's Discretion0112000
Overall StudyLost to Follow-up0021300
Overall StudyNon Compliance with Study Drug1000000
Overall StudyProtocol Violation0000110
Overall StudyRandomized but Never Treated0011100
Overall StudyUnknown Reason33111220
Overall StudyWithdrew Consent1314441

Baseline characteristics

CharacteristicFirsocostatTotalPlaceboFIR + CILOSelonsertibSEL + CILOSEL + FIRCilofexor
Age, Continuous60 years
STANDARD_DEVIATION 10
60 years
STANDARD_DEVIATION 9
61 years
STANDARD_DEVIATION 8.2
61 years
STANDARD_DEVIATION 8.4
59 years
STANDARD_DEVIATION 10.4
60 years
STANDARD_DEVIATION 9
59 years
STANDARD_DEVIATION 8.3
57 years
STANDARD_DEVIATION 10.2
Cirrhosis Status
Cirrhotic
22 Participants221 Participants22 Participants42 Participants21 Participants46 Participants46 Participants22 Participants
Cirrhosis Status
Non-Cirrhotic
18 Participants171 Participants17 Participants36 Participants18 Participants31 Participants33 Participants18 Participants
Diabetes Mellitus Status
Absent
10 Participants110 Participants12 Participants21 Participants13 Participants19 Participants22 Participants13 Participants
Diabetes Mellitus Status
Present
30 Participants282 Participants27 Participants57 Participants26 Participants58 Participants57 Participants27 Participants
Race/Ethnicity, Customized
Ethinicity
Hispanic or Latino
9 Participants105 Participants14 Participants17 Participants8 Participants25 Participants18 Participants14 Participants
Race/Ethnicity, Customized
Ethinicity
Not Hispanic or Latino
31 Participants285 Participants25 Participants60 Participants31 Participants52 Participants60 Participants26 Participants
Race/Ethnicity, Customized
Ethinicity
Not Permitted
0 Participants2 Participants0 Participants1 Participants0 Participants0 Participants1 Participants0 Participants
Race/Ethnicity, Customized
Race
American Indian or Alaska Native
0 Participants4 Participants0 Participants1 Participants1 Participants1 Participants1 Participants0 Participants
Race/Ethnicity, Customized
Race
Asian
3 Participants25 Participants3 Participants5 Participants7 Participants4 Participants3 Participants0 Participants
Race/Ethnicity, Customized
Race
Black
1 Participants7 Participants1 Participants2 Participants0 Participants2 Participants1 Participants0 Participants
Race/Ethnicity, Customized
Race
Native Hawaiian or Pacific Islander
1 Participants1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race/Ethnicity, Customized
Race
Not Permitted
0 Participants1 Participants0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants
Race/Ethnicity, Customized
Race
Other
0 Participants5 Participants0 Participants2 Participants0 Participants2 Participants1 Participants0 Participants
Race/Ethnicity, Customized
Race
White
35 Participants349 Participants35 Participants68 Participants30 Participants68 Participants73 Participants40 Participants
Region of Enrollment
Australia
3 participants23 participants0 participants7 participants3 participants5 participants4 participants1 participants
Region of Enrollment
Canada
2 participants22 participants3 participants3 participants3 participants4 participants5 participants2 participants
Region of Enrollment
Hong Kong
0 participants10 participants1 participants2 participants2 participants2 participants3 participants0 participants
Region of Enrollment
New Zealand
0 participants1 participants0 participants0 participants1 participants0 participants0 participants0 participants
Region of Enrollment
United States
35 participants336 participants35 participants66 participants30 participants66 participants67 participants37 participants
Sex: Female, Male
Female
25 Participants253 Participants27 Participants48 Participants24 Participants51 Participants49 Participants29 Participants
Sex: Female, Male
Male
15 Participants139 Participants12 Participants30 Participants15 Participants26 Participants30 Participants11 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
EG004
affected / at risk
EG005
affected / at risk
EG006
affected / at risk
deaths
Total, all-cause mortality
0 / 390 / 400 / 400 / 791 / 770 / 780 / 39
other
Total, other adverse events
30 / 3930 / 4034 / 4067 / 7968 / 7766 / 7829 / 39
serious
Total, serious adverse events
7 / 393 / 408 / 407 / 7910 / 778 / 782 / 39

Outcome results

Primary

Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)

Time frame: First dose date up to 48 weeks plus 30 days

Population: The Safety Analysis Set included all participants who took at least 1 dose of study drug.

ArmMeasureValue (NUMBER)
SelonsertibPercentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)84.6 percentage of participants
FirsocostatPercentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)85.0 percentage of participants
CilofexorPercentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)92.5 percentage of participants
SEL + FIRPercentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)88.6 percentage of participants
SEL + CILOPercentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)96.1 percentage of participants
FIR + CILOPercentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)91.0 percentage of participants
PlaceboPercentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)79.5 percentage of participants
Primary

Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities

Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. Participants with any laboratory abnormality were reported.

Time frame: First dose date up to 48 weeks plus 30 days

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

ArmMeasureValue (NUMBER)
SelonsertibPercentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities94.9 percentage of participants
FirsocostatPercentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities100.0 percentage of participants
CilofexorPercentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities97.5 percentage of participants
SEL + FIRPercentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities98.7 percentage of participants
SEL + CILOPercentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities96.1 percentage of participants
FIR + CILOPercentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities100.0 percentage of participants
PlaceboPercentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities94.9 percentage of participants
Primary

Percentage of Participants Who Achieved a ≥ 1-Stage Improvement in Fibrosis Without Worsening of NASH at Week 48

Fibrosis improvement was defined as ≥ 1-stage decrease from baseline in fibrosis according to the NASH clinical research network classification (CRN) classification. Worsening of NASH was defined as ≥ 1-point increase from baseline in hepatocellular ballooning or lobular inflammation. The 95% CI was based on the Clopper-Pearson method.

Time frame: Week 48

Population: Participants in the Full Analysis Set (included all participants who took at least 1 dose of study drug and were randomized into the study) with available data were analyzed.

ArmMeasureValue (NUMBER)
SelonsertibPercentage of Participants Who Achieved a ≥ 1-Stage Improvement in Fibrosis Without Worsening of NASH at Week 4828.6 percentage of participants
FirsocostatPercentage of Participants Who Achieved a ≥ 1-Stage Improvement in Fibrosis Without Worsening of NASH at Week 4812.1 percentage of participants
CilofexorPercentage of Participants Who Achieved a ≥ 1-Stage Improvement in Fibrosis Without Worsening of NASH at Week 4811.8 percentage of participants
SEL + FIRPercentage of Participants Who Achieved a ≥ 1-Stage Improvement in Fibrosis Without Worsening of NASH at Week 4815.5 percentage of participants
SEL + CILOPercentage of Participants Who Achieved a ≥ 1-Stage Improvement in Fibrosis Without Worsening of NASH at Week 4819.1 percentage of participants
FIR + CILOPercentage of Participants Who Achieved a ≥ 1-Stage Improvement in Fibrosis Without Worsening of NASH at Week 4820.9 percentage of participants
PlaceboPercentage of Participants Who Achieved a ≥ 1-Stage Improvement in Fibrosis Without Worsening of NASH at Week 4810.5 percentage of participants
p-value: 0.944995% CI: [-17.6, 18.8]Mantel Haenszel
p-value: 0.964695% CI: [-17.6, 18.4]Mantel Haenszel
p-value: 0.621995% CI: [-10.9, 18.3]Mantel Haenszel
p-value: 0.255495% CI: [-6.4, 24.1]Mantel Haenszel
p-value: 0.165895% CI: [-4.5, 26.1]Mantel Haenszel
p-value: 0.696395% CI: [-12.9, 19.4]Mantel Haenszel
p-value: 0.244195% CI: [-6.8, 26.8]Mantel Haenszel
p-value: 0.522995% CI: [-10.7, 21]Mantel Haenszel
p-value: 0.214995% CI: [-6, 26.9]Mantel Haenszel

Source: ClinicalTrials.gov · Data processed: Feb 15, 2026