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)

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

Timeline

Start

2018-03-21

Primary completion

2019-10-30

Completion

2019-11-19

Outcome

Missed primary endpoint

registry analysis (superiority test); FIR + CILO vs Placebo; p = 0.1658; Difference in percentages 10.8 (95% CI -4.5 to 26.1) NCT03449446 ↗

paper The primary endpoint was achieved in 11% of placebo-treated patients versus cilofexor/firsocostat (21%; P = 0.17) PMID 33169409 ↗

Publications

• Results 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Cilofexor	Small molecule	30 mg	Oral
Subject	Firsocostat	Small molecule	20 mg	Oral
Subject	Selonsertib	Small molecule	18 mg	Oral

Indications