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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03449446




Registration number
NCT03449446
Ethics application status
Date submitted
23/02/2018
Date registered
28/02/2018
Date last updated
3/12/2020

Titles & IDs
Public title
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)
Scientific title
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)
Secondary ID [1] 0 0
GS-US-454-4378
Universal Trial Number (UTN)
Trial acronym
ATLAS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Nonalcoholic Steatohepatitis 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Diet and Nutrition 0 0 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SEL
Treatment: Drugs - FIR
Treatment: Drugs - CILO
Treatment: Drugs - Placebo to match FIR
Treatment: Drugs - Placebo to match CILO
Treatment: Drugs - Placebo to match SEL

Experimental: Selonsertib (SEL) - Participants will receive SEL + placebo to match firsocostat 20 mg tablet + placebo to match cilofexor 30 mg tablet orally once daily for 48 weeks.

Experimental: Firsocostat (FIR) - Participants will receive placebo to match SEL 18 mg tablet + FIR + placebo to match CILO 30 mg tablet orally once daily for 48 weeks.

Experimental: Cilofexor (CILO) - Participants will receive placebo to match SEL 18 mg tablet + placebo to match FIR 20 mg tablet + CILO orally once daily for 48 weeks.

Experimental: Selonsertib (SEL) + Firsocostat (FIR) - Participants will receive SEL + FIR + placebo to match CILO 30 mg tablet orally once daily for 48 weeks.

Experimental: Selonsertib (SEL) + Cilofexor (CILO) - Participants will receive SEL + placebo to match FIR 20 mg tablet + CILO orally once daily for 48 weeks.

Experimental: Firsocostat (FIR) + Cilofexor (CILO) - Participants will receive placebo to match SEL 18 mg tablet + FIR + CILO orally once daily for 48 weeks.

Experimental: Placebo - Participants will receive placebo to match SEL 18 mg + placebo to match FIR 20 mg tablet + placebo to match CILO 30 mg tablet orally once daily for 48 weeks.


Treatment: Drugs: SEL
18 mg tablet administered orally once daily without regard to food

Treatment: Drugs: FIR
20 mg tablet administered orally once daily without regard to food

Treatment: Drugs: CILO
30 mg tablet administered orally once daily without regard to food

Treatment: Drugs: Placebo to match FIR
Tablet administered orally once daily without regard to food

Treatment: Drugs: Placebo to match CILO
Tablet administered orally once daily without regard to food

Treatment: Drugs: Placebo to match SEL
Tablet administered orally once daily without regard to food
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
Timepoint [1] 0 0
First dose date up to 48 weeks plus 30 days
Primary outcome [2] 0 0
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities
Timepoint [2] 0 0
First dose date up to 48 weeks plus 30 days
Primary outcome [3] 0 0
Percentage of Participants Who Achieved a = 1-Stage Improvement in Fibrosis Without Worsening of NASH at Week 48
Timepoint [3] 0 0
Week 48

Eligibility
Key inclusion criteria
Key

* 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
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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/ Exclusion criteria may apply

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
21/03/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
19/11/2019
Sample size
Target
Accrual to date
Final
395
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Royal Brisbane & Women's Hospital - Herston
Recruitment hospital [2] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 0 0
Monash Health, Monash Medical Centre - Clayton
Recruitment hospital [4] 0 0
St Vincent's Hospital Melbourne - Fitzroy
Recruitment hospital [5] 0 0
Melbourne Health, Royal Melbourne Hospital - Parkville
Recruitment hospital [6] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [7] 0 0
Royal Perth Hospital - Perth
Recruitment hospital [8] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [9] 0 0
St Vincent's Hospital Sydney - Darlinghurst
Recruitment hospital [10] 0 0
Austin Health - Heidelberg
Recruitment hospital [11] 0 0
The Alfred Hospital, Alfred Health - Melbourne
Recruitment hospital [12] 0 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3065 - Fitzroy
Recruitment postcode(s) [5] 0 0
3050 - Parkville
Recruitment postcode(s) [6] 0 0
6009 - Nedlands
Recruitment postcode(s) [7] 0 0
6000 - Perth
Recruitment postcode(s) [8] 0 0
2050 - Camperdown
Recruitment postcode(s) [9] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [10] 0 0
3084 - Heidelberg
Recruitment postcode(s) [11] 0 0
3004 - Melbourne
Recruitment postcode(s) [12] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Iowa
Country [10] 0 0
United States of America
State/province [10] 0 0
Kansas
Country [11] 0 0
United States of America
State/province [11] 0 0
Louisiana
Country [12] 0 0
United States of America
State/province [12] 0 0
Maryland
Country [13] 0 0
United States of America
State/province [13] 0 0
Massachusetts
Country [14] 0 0
United States of America
State/province [14] 0 0
Michigan
Country [15] 0 0
United States of America
State/province [15] 0 0
Minnesota
Country [16] 0 0
United States of America
State/province [16] 0 0
Mississippi
Country [17] 0 0
United States of America
State/province [17] 0 0
Missouri
Country [18] 0 0
United States of America
State/province [18] 0 0
Nevada
Country [19] 0 0
United States of America
State/province [19] 0 0
New Jersey
Country [20] 0 0
United States of America
State/province [20] 0 0
New York
Country [21] 0 0
United States of America
State/province [21] 0 0
North Carolina
Country [22] 0 0
United States of America
State/province [22] 0 0
Ohio
Country [23] 0 0
United States of America
State/province [23] 0 0
Pennsylvania
Country [24] 0 0
United States of America
State/province [24] 0 0
Rhode Island
Country [25] 0 0
United States of America
State/province [25] 0 0
South Carolina
Country [26] 0 0
United States of America
State/province [26] 0 0
Tennessee
Country [27] 0 0
United States of America
State/province [27] 0 0
Texas
Country [28] 0 0
United States of America
State/province [28] 0 0
Utah
Country [29] 0 0
United States of America
State/province [29] 0 0
Virginia
Country [30] 0 0
United States of America
State/province [30] 0 0
Washington
Country [31] 0 0
Canada
State/province [31] 0 0
Brampton
Country [32] 0 0
Canada
State/province [32] 0 0
Calgary
Country [33] 0 0
Canada
State/province [33] 0 0
Montreal
Country [34] 0 0
Canada
State/province [34] 0 0
Toronto
Country [35] 0 0
Hong Kong
State/province [35] 0 0
Shatin
Country [36] 0 0
New Zealand
State/province [36] 0 0
Auckland
Country [37] 0 0
Puerto Rico
State/province [37] 0 0
San Juan

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/study/NCT03449446
Trial related presentations / publications
Loomba R, et al. Safety and efficacy of combination therapies including cilofexor/firsocostat in patients with bridging fibrosis and cirrhosis due to NASH: Results of the Phase 2b ATLAS trial [accepted for oral presentation]. European Association for the Study of the Liver (EASL); 2020; Virtual.
Loomba R, Alkhouri N, Strasser S, Wong VWS, Schall RA, McColgan B, et al. Clinical utility and application of non-invasive tests of fibrosis in the selection of patients with advanced fibrosis due to NASH in the Phase 2 ATLAS trial (Poster SAT-315). EASL; 2019; Vienna, Austria.
Loomba R, Alkhouri N, Patel K, Zhang J, McColgan BJ, Djedjos S, et al. Validation of Cutoffs for Controlled Attenuation Parameter with MRI-Proton Density Fat Fraction (PDFF) as a Reference Standard in Subjects with Nonalcoholic Steatohepatitis (NASH) Across Multiple Randomized, Controlled Trials (Poster 1727). American Association for the Study of Liver Diseases (AASLD); 2019; Boston, MA, USA.
Loomba R, Alkhouri N, Noureddin M, Zhang J, McColgan BJ, Djedjos S, et al. Validation of the Diagnostic Accuracy of Magnetic Resonance Elastography (MRE) for the Detection of Advanced Fibrosis Due to Nash Across Multiple Phase 2 and 3 Clinical Trials (Poster 1728). AASLD; 2019; Boston, MA, USA.
Alkhouri N, Strasser SI, Wong VWS, Aguilar R, Chuang J, Huss R, et al. Alcohol use is Underreported in Clinical Trials of NASH: Baseline Alcohol Biomarkers from a Phase 2 Clinical Trial (Poster 1765). AASLD; 2019; Boston, MA, USA.
Loomba R, Noureddin M, Kowdley KV, Kohli A, Sheikh A, Neff G, Bhandari BR, Gunn N, Caldwell SH, Goodman Z, Wapinski I, Resnick M, Beck AH, Ding D, Jia C, Chuang JC, Huss RS, Chung C, Subramanian GM, Myers RP, Patel K, Borg BB, Ghalib R, Kabler H, Poulos J, Younes Z, Elkhashab M, Hassanein T, Iyer R, Ruane P, Shiffman ML, Strasser S, Wong VW, Alkhouri N; for the ATLAS Investigators. Combination Therapies Including Cilofexor and Firsocostat for Bridging Fibrosis and Cirrhosis Attributable to NASH. Hepatology. 2021 Feb;73(2):625-643. doi: 10.1002/hep.31622.
Public notes

Contacts
Principal investigator
Name 0 0
Gilead Study Director
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03449446