Simtuzumab (GS-6624) in the Prevention of Progression of Liver Fibrosis in Adults With Primary Sclerosing Cholangitis (PSC)

Summary

The purpose of this study is to evaluate whether simtuzumab (GS-6624) is effective at preventing the progression of liver fibrosis in adults with primary sclerosing cholangitis (PSC).

Timeline

Start

2013-03-04

Primary completion

2016-08-08

Completion

2016-08-24

Publications

• Results Shea P, Hirschfield G, Shiffman M, McColgan B, Goodman Z, Myers, R, et al. Common variation near glial-derived neurotrophic factor is associated with progression of hepatic collagen content in a genome-wide association study of liver fibrosis phenotypes in patients with primary sclerosing cholangitis. J Hepatol 2017; 66 (1): S4-S5.
• Results Muir A, Goodman Z, Levy C, Janssen H, Montano-Loza A, Bowlus C, et al. Efficacy and safety of simtuzumab for the treatment of primary sclerosing cholangitis: results of a phase 2b, dose-ranging, randomized, placebo-controlled trial. J Hepatol 2017; 66 (1): S73.
• Results Bowlus CL, Patel K, Hirschfield G, Guha I, Chapman R, Chazouilleres O, et al. Prospective validation of the Enhanced Liver Fibrosis test for the prediction of disease progression in a randomized trial of patients with primary sclerosing cholangitis. J Hepatol 2017; 66 (1): S359.
• Results Levy C, Eksteen B, Shiffman M, Janssen H, Montano-Loza A, Ding D, et al. Prospective validation of serum alkaline phosphatase for the prediction of disease progression in a randomized trial of patients with primary sclerosing cholangitis. J Hepatol 2017; 66 (1): S360-S361.
• Results Levy C, Shiffman M, Caldwell S, Luketic V, Invernizzi P, Minuk G, et al. Serum fibroblast growth factor 19, 7α-Hydroxy-4-Cholesten-3-one, and bile acids and their associations with clinical characteristics in primary sclerosing cholangitis. J Hepatol 2017; 66 (1): S361.
• Results French D, Huntzicker EG, Goodman ZD, Shea PR, Ding D, Aguilar Schall, RE, et al. Hepatic expression of lysyl oxidase-like-2 (LOXL2) in primary sclerosing cholangitis (PSC). Hepatol 2016; 64 (1): 194A.
• Results Bowlus CL, Montano-Loza AJ, Invernizzi P, Chazouilleres O, Hirschfield G, Metselaar HJ, et al. Liver stiffness measurement by transient elastography for the prediction of fibrosis in patients with primary sclerosing cholangitis in a randomized trial of simtuzumab. J Hepatol 2016; 64 (2): S434.
• Results Goodman Z, Patel K, Guha I, Hameed B, Kowdley K, Alaparthi L, et al. Correlations between hepatic morphometric collagen content, histologic fibrosis stage, and serum markers in patients with primary sclerosing cholangitis (PSC). J Hepatol 2016; 64 (2): S652-S653.
• Results Muir AJ, Goodman Z, Bowlus CL, Caldwell S, Invernizzi P, Luketic V, et al. Serum lysyl oxidase-like-2 (SLOXL2) levels correlate with disease severity in patients with primary sclerosing cholangitis. J Hepatol 2016; 64 (2): S428.
• Results Shea PR, Eksteen B, Hirschfield GM, Shiffman ML, Janssen HLA, Montano-Loza AJ, et al. Genome-wide association study (GWAS) of liver fibrosis phenotypes in patients with primary sclerosing cholangitis (PSC) reveals common genetic variation influencing serum levels of lysyl oxidase-like-2 (LOXL2). J Hepatol 2016; 64 (2): S180-S182.
• Results Manns MP, Eksteen B, Shiffman ML, Levy C, Kowdley KV, Montano-Loza AJ, et al. Association between elevated serum IgG4 (sIgG4) concentrations and the phenotype of patients with primary sclerosing cholangitis (PSC). Hepatol 2015; 62 (1): 515A.
• Results Bowlus CL, Patel K, Chuha IN, Chapman RW, Chazouilleres O, Chalasani NP, et al. Validation of serum fibrosis marker panels in patients with primary sclerosing cholangitis (PSC) in a randomized trial of simtuzumab. Hepatol 2015; 62 (1): 519A.
• Results French D, Goodman ZD, Huntzicker EG, Newstrom D, Karnik S, Smith V, et al. Expression of matrix metalloproteinase 9 (MMP9) and the apoptosis signal-regulating kinase 1 (ASK1) pathway activation marker, phospho-P38 (p-P38), in primary sclerosing cholangitis (PSC). Hepatol 2015; 62 (1): 523A-524A.
• Laschtowitz A, Lindberg EL, Liebhoff AM, Liebig LA, Casar C, Steinmann S, Guillot A, Xu J, Schwinge D, Trauner M, Lohse AW, Bonn S, Hubner N, Schramm C. Liver transcriptome analysis reveals PSC-attributed gene set associated with fibrosis progression. JHEP Rep. 2024 Nov 12;7(3):101267. doi: 10.1016/j.jhepr.2024.101267. eCollection 2025 Mar.
• Thorburn D, Leeming DJ, Barchuk WT, Wang Y, Lu X, Malkov VA, Ito KL, Bowlus CL, Levy C, Goodman Z, Karsdal MA, Muir AJ, Xu J. Serologic extracellular matrix remodeling markers are related to fibrosis stage and prognosis in a phase 2b trial of simtuzumab in patients with primary sclerosing cholangitis. Hepatol Commun. 2024 Jul 5;8(7):e0467. doi: 10.1097/HC9.0000000000000467. eCollection 2024 Jul 1.
• Muir AJ, Levy C, Janssen HLA, Montano-Loza AJ, Shiffman ML, Caldwell S, Luketic V, Ding D, Jia C, McColgan BJ, McHutchison JG, Mani Subramanian G, Myers RP, Manns M, Chapman R, Afdhal NH, Goodman Z, Eksteen B, Bowlus CL; GS-US-321-0102 Investigators. Simtuzumab for Primary Sclerosing Cholangitis: Phase 2 Study Results With Insights on the Natural History of the Disease. Hepatology. 2019 Feb;69(2):684-698. doi: 10.1002/hep.30237. Epub 2019 Jan 11.

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Indications