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Cilofexor, a Nonsteroidal FXR Agonist, in Patients With Noncirrhotic NASH: A Phase 2 Randomized Controlled Trial.

Publication ,  Journal Article
Patel, K; Harrison, SA; Elkhashab, M; Trotter, JF; Herring, R; Rojter, SE; Kayali, Z; Wong, VW-S; Greenbloom, S; Jayakumar, S; Shiffman, ML ...
Published in: Hepatology
July 2020

BACKGROUND AND AIMS: We evaluated the safety and efficacy of cilofexor (formerly GS-9674), a small-molecule nonsteroidal agonist of farnesoid X receptor, in patients with nonalcoholic steatohepatitis (NASH). APPROACH AND RESULTS: In this double-blind, placebo-controlled, phase 2 trial, 140 patients with noncirrhotic NASH, diagnosed by magnetic resonance imaging-proton density fat fraction (MRI-PDFF) ≥8% and liver stiffness ≥2.5 kPa by magnetic resonance elastography (MRE) or historical liver biopsy, were randomized to receive cilofexor 100 mg (n = 56), 30 mg (n = 56), or placebo (n = 28) orally once daily for 24 weeks. MRI-PDFF, liver stiffness by MRE and transient elastography, and serum markers of fibrosis were measured at baseline and week 24. At baseline, median MRI-PDFF was 16.3% and MRE-stiffness was 3.27 kPa. At week 24, patients receiving cilofexor 100 mg had a median relative decrease in MRI-PDFF of -22.7%, compared with an increase of 1.9% in those receiving placebo (P = 0.003); the 30-mg group had a relative decrease of -1.8% (P = 0.17 vs. placebo). Declines in MRI-PDFF of ≥30% were experienced by 39% of patients receiving cilofexor 100 mg (P = 0.011 vs. placebo), 14% of those receiving cilofexor 30 mg (P = 0.87 vs. placebo), and 13% of those receiving placebo. Serum gamma-glutamyltransferase, C4, and primary bile acids decreased significantly at week 24 in both cilofexor treatment groups, whereas significant changes in Enhanced Liver Fibrosis scores and liver stiffness were not observed. Cilofexor was generally well-tolerated. Moderate to severe pruritus was more common in patients receiving cilofexor 100 mg (14%) than in those receiving cilofexor 30 mg (4%) and placebo (4%). CONCLUSIONS: Cilofexor for 24 weeks was well-tolerated and provided significant reductions in hepatic steatosis, liver biochemistry, and serum bile acids in patients with NASH. ClinicalTrials.gov No. NCT02854605.

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Published In

Hepatology

DOI

EISSN

1527-3350

Publication Date

July 2020

Volume

72

Issue

1

Start / End Page

58 / 71

Location

United States

Related Subject Headings

  • Young Adult
  • Treatment Outcome
  • Receptors, Cytoplasmic and Nuclear
  • Non-alcoholic Fatty Liver Disease
  • Middle Aged
  • Male
  • Isonicotinic Acids
  • Humans
  • Gastroenterology & Hepatology
  • Female
 

Citation

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Patel, K., Harrison, S. A., Elkhashab, M., Trotter, J. F., Herring, R., Rojter, S. E., … Noureddin, M. (2020). Cilofexor, a Nonsteroidal FXR Agonist, in Patients With Noncirrhotic NASH: A Phase 2 Randomized Controlled Trial. Hepatology, 72(1), 58–71. https://doi.org/10.1002/hep.31205
Patel, Keyur, Stephen A. Harrison, Magdy Elkhashab, James F. Trotter, Robert Herring, Sergio E. Rojter, Zeid Kayali, et al. “Cilofexor, a Nonsteroidal FXR Agonist, in Patients With Noncirrhotic NASH: A Phase 2 Randomized Controlled Trial.Hepatology 72, no. 1 (July 2020): 58–71. https://doi.org/10.1002/hep.31205.
Patel K, Harrison SA, Elkhashab M, Trotter JF, Herring R, Rojter SE, et al. Cilofexor, a Nonsteroidal FXR Agonist, in Patients With Noncirrhotic NASH: A Phase 2 Randomized Controlled Trial. Hepatology. 2020 Jul;72(1):58–71.
Patel, Keyur, et al. “Cilofexor, a Nonsteroidal FXR Agonist, in Patients With Noncirrhotic NASH: A Phase 2 Randomized Controlled Trial.Hepatology, vol. 72, no. 1, July 2020, pp. 58–71. Pubmed, doi:10.1002/hep.31205.
Patel K, Harrison SA, Elkhashab M, Trotter JF, Herring R, Rojter SE, Kayali Z, Wong VW-S, Greenbloom S, Jayakumar S, Shiffman ML, Freilich B, Lawitz EJ, Gane EJ, Harting E, Xu J, Billin AN, Chung C, Djedjos CS, Subramanian GM, Myers RP, Middleton MS, Rinella M, Noureddin M. Cilofexor, a Nonsteroidal FXR Agonist, in Patients With Noncirrhotic NASH: A Phase 2 Randomized Controlled Trial. Hepatology. 2020 Jul;72(1):58–71.
Journal cover image

Published In

Hepatology

DOI

EISSN

1527-3350

Publication Date

July 2020

Volume

72

Issue

1

Start / End Page

58 / 71

Location

United States

Related Subject Headings

  • Young Adult
  • Treatment Outcome
  • Receptors, Cytoplasmic and Nuclear
  • Non-alcoholic Fatty Liver Disease
  • Middle Aged
  • Male
  • Isonicotinic Acids
  • Humans
  • Gastroenterology & Hepatology
  • Female