Simtuzumab (GS-6624) in the Prevention of Progression of Liver Fibrosis in Adults With Primary Sclerosing Cholangitis (PSC)
NCT ID: NCT01672853
Last Updated: 2019-10-22
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
235 participants
INTERVENTIONAL
2013-03-04
2016-08-24
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
PREVENTION
TRIPLE
Study Groups
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Treatment Arm A
Simtuzumab 75 mg for 96 weeks
Simtuzumab
Subcutaneous injections weekly for a total of 96 injections
Treatment Arm B
Simtuzumab 125 mg for 96 weeks
Simtuzumab
Subcutaneous injections weekly for a total of 96 injections
Treatment Arm C
Placebo for 96 weeks
Placebo
Subcutaneous injections weekly for a total of 96 injections
Interventions
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Simtuzumab
Subcutaneous injections weekly for a total of 96 injections
Placebo
Subcutaneous injections weekly for a total of 96 injections
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Liver biopsy consistent with PSC: If a liver biopsy has been performed within 3 months of the screening visit, tissue from that biopsy may be used as the screening biopsy. Slides would be re-cut from the existing tissue block and submitted for central reader assessment. Some individuals with PSC may have a normal liver biopsy, in the event of a normal liver biopsy, the individual must have an abnormal magnetic resonance cholangiopancreatography (MRCP).
* MRCP consistent with PSC: Some individuals with PSC may have a normal MRCP; in the event of a normal MRCP, the individual must have an abnormal liver biopsy.
* Exclusion of other causes of liver disease including viral hepatitis ,alcoholic liver disease,primary biliary cirrhosis and secondary sclerosing cholangitis
* Must have aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 10 x the Central Laboratory Upper Limit of Normal (clULN)
* Must have serum creatinine \< 2.0 mg/dL
* A negative serum pregnancy test is required for female individuals of childbearing potential
* All sexually active female individuals of childbearing potential must agree to use a protocol recommended method of contraception during heterosexual intercourse throughout the study and for 90 days following the last dose of study medication
* Lactating females must agree to discontinue nursing before starting study treatment
* Males if not vasectomized, are required to use barrier contraception (condom plus spermicide) during intercourse from the screening through the study completion and for 90 days following the last dose of study drug
Exclusion Criteria
* Evidence of hepatic decompensation present, including ascites, episodes of hepatic encephalopathy, variceal bleeding or a prolonged prothrombin time/international normalized ratio (PT/INR)
* Positive for hepatitis C virus (HCV) RNA
* Positive for HBsAg
* Positive for anti-mitochondrial antibody
* Alcohol consumption greater than 21oz/week for males or 14oz/week for females
* Moderately active ulcerative colitis (UC) defined as either a partial Mayo score of \> 4, bleeding score of \>1, or current use of oral corticosteroid therapy and/or any inhibitor of Tumor necrosis factor-α (TNF-α) or α4β7 integrin antagonist
* Positive urine screen for amphetamines, cocaine or opiates (i.e. heroin, morphine) at screening. Individuals on stable methadone or buprenorphine maintenance treatment for at least 6 months prior to screening may be included in the study. Individuals with a positive urine drug screen due to prescription opioid-based medication are eligible if the prescription and diagnosis are reviewed and approved by the investigator
* Clinically significant cardiac disease
* History of cholangiocarcinoma
* History of other cancers,other than non-melanomatous skin cancer, within 5 years prior to screening
* Ascending cholangitis within 60 days of screening
* Presence of a percutaneous drain or bile duct stent
* Known hypersensitivity to the investigation product or any of its formulation excipients
* History of bleeding diathesis within 6 months of screening
* Unavailable for follow-up assessment or concern for individual's compliance with the protocol procedures;
* Participation in an investigational trial of a drug or device within 30 days prior to screening
* Major surgical procedure within 30 days prior to screening or the presence of an open wound
18 Years
70 Years
ALL
No
Sponsors
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Gilead Sciences
INDUSTRY
Responsible Party
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Principal Investigators
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Gilead Study Director
Role: STUDY_DIRECTOR
Gilead Sciences
Locations
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Mayo Clinic Hospital
Phoenix, Arizona, United States
University of Arizona Health Sciences Center
Tucson, Arizona, United States
Southern California Liver Center
Chula Vista, California, United States
Southern California Liver Centers
Coronado, California, United States
Scripps Clinic
La Jolla, California, United States
Verterans Adminstration Hospital
Palo Alto, California, United States
UC Davis Medical Center
Sacramento, California, United States
University of San Diego Medical Center
San Diego, California, United States
University of California San Francisco
San Francisco, California, United States
University of Colorado Denver
Aurora, Colorado, United States
University of Miami Center for Liver Diseases
Miami, Florida, United States
Northwestern University
Chicago, Illinois, United States
Indiana University
Indianapolis, Indiana, United States
Indianapolis Gastroenterology Research Foundation
Indianapolis, Indiana, United States
Iowa Digestive Disease Center
Clive, Iowa, United States
University of Louisville
Louisville, Kentucky, United States
Tulane University Health Sciences Center
New Orleans, Louisiana, United States
Walter Reed National Military Medical Center
Bethesda, Maryland, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Minnesota Gastroenterology, PA
Saint Paul, Minnesota, United States
St. Louis University
St Louis, Missouri, United States
Weill Cornell Medical College
New York, New York, United States
Mount Sinai Hospital
New York, New York, United States
Duke Clinical Research Institute
Durham, North Carolina, United States
University Hospitals Case Medical Center
Cleveland, Ohio, United States
Cleveland Clinic
Cleveland, Ohio, United States
University of Pennsylvania
Philadelphia, Pennsylvania, United States
University Gastroenterology
Providence, Rhode Island, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
UT Southwestern Medical Center
Dallas, Texas, United States
Brooke Army Medical Center
Fort Sam Houston, Texas, United States
St. Luke Episcopal Hospital
Houston, Texas, United States
Alamo Medical Research
San Antonio, Texas, United States
Intermountain Medical Center
Murray, Utah, United States
University of Utah
Salt Lake City, Utah, United States
University of Virginia Health Center
Charlottesville, Virginia, United States
Liver Institute of Virginia
Newport News, Virginia, United States
Digestive and Liver Disease Specialists
Norfolk, Virginia, United States
Bon Secours Richmond Health System
Richmond, Virginia, United States
Virginia Commonwealth University Health System
Richmond, Virginia, United States
Virginia Mason Medical Center
Seattle, Washington, United States
University of Washington
Seattle, Washington, United States
Hôpital Erasme
Brussels, , Belgium
Université Catholique de Louvain
Brussels, , Belgium
UZ Antwerpen
Edegem, , Belgium
UZ Gent
Ghent, , Belgium
UZ Leuven
Leuven, , Belgium
University of Calgary
Calgary, Alberta, Canada
University of Alberta
Edmonton, Alberta, Canada
University of Manitoba
Winnepeg, Manitoba, Canada
Dalhousie University
Halifax, Nova Scotia, Canada
London Health Science Center
London, Ontario, Canada
Toronto Liver Centre
Toronto, Ontario, Canada
Århus Universitetshospital, Århus Sygehus
Århus C, , Denmark
Hvidovre Hospital
Hvidovre, , Denmark
Rigshospitalet
København Ø, , Denmark
Klinikum der Johann Wolfgang Goethe Universitat
Frankfurt, , Germany
Medizinische Hochschule Hannover
Hanover, , Germany
Gastroenterologisch Hepatologisches Zentrum Kiel
Kiel, , Germany
EUGASTRO GmbH
Leipzig, , Germany
Istituto Clinico Humanitas
Rozzano, Milano, Italy
Azienda Ospedaliera San Camillo Forlanini
Roma, , Italy
Azienda Ospedaliera Città della Salute e della Scienza di Torino
Torino, , Italy
Eramus MC
Rotterdam, , Netherlands
Hospital Universitario Vall d'Hebron
Barcelona, Catalonia, Spain
Hospital Donostia
Donostia / San Sebastian, , Spain
Hospital Universitario Puerta de Hierro
Majadahonda, , Spain
Avd för invärtesmedicin och klinisk nutrition
Gothenburg, , Sweden
New Queen Elizabeth Hospital
Birmingham, , United Kingdom
John Radcliffe Hospital
Headington, , United Kingdom
Imperial College Healthcare NHS Trust- St. Mary's Hospital
London, , United Kingdom
University College London
London, , United Kingdom
Norfolk and Norwich University Hospital
Norwich, , United Kingdom
University of Nottingham
Nottingham, , United Kingdom
Countries
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References
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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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Other Identifiers
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2012-002473-61
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
GS-US-321-0102
Identifier Type: -
Identifier Source: org_study_id
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