Safety and Efficacy of Simtuzumab (SIM, GS-6624) in Adults With Advanced Liver Fibrosis But Not Cirrhosis Secondary to Non-Alcoholic Steatohepatitis (NASH)
NCT ID: NCT01672866
Last Updated: 2019-03-27
Study Results
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View full resultsBasic Information
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TERMINATED
PHASE2
222 participants
INTERVENTIONAL
2012-12-05
2016-12-29
Brief Summary
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It will consist of 2 phases:
* Randomized Double-Blind Phase
* Open-Label Phase (optional)
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Study Groups
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SIM 75 mg
During the Randomized Double-Blind Phase, participants will receive SIM 75 mg via subcutaneous injection once weekly for up to 240 weeks. During the optional Open-Label Phase, participants will receive SIM 125 mg via subcutaneous injection once weekly for up to an additional 240 weeks.
SIM
Subcutaneous injection every week
SIM 125 mg
During the Randomized Double-Blind Phase, participants will receive SIM 125 mg via subcutaneous injection once weekly for up to 240 weeks. During the optional Open-Label Phase, participants will receive SIM 125 mg via subcutaneous injection once weekly for up to an additional 240 weeks.
SIM
Subcutaneous injection every week
Placebo
During the Randomized Double-Blind Phase, participants will receive placebo to match SIM via subcutaneous injection once weekly for up to 240 weeks. During the optional Open-Label Phase, participants will receive SIM 125 mg via subcutaneous injection once weekly for up to an additional 240 weeks.
Placebo
Placebo to match SIM via subcutaneous injection every week
SIM
Subcutaneous injection every week
Interventions
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Placebo
Placebo to match SIM via subcutaneous injection every week
SIM
Subcutaneous injection every week
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Stage 3-4 fibrosis by Ishak score on a liver biopsy
* Exclusion of other causes of liver disease including viral hepatitis and alcoholic liver disease
* Must have aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 10 x Central Laboratory Upper Limit of Normal (clULN)
* Must have serum creatinine \< 2.0 mg/dL
* A negative serum pregnancy test is required for females of childbearing potential
* All sexually active females of childbearing potential must agree to use a protocol recommended method of contraception during 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 heterosexual intercourse from the screening through the study completion and for 90 days following the last dose of study drug.
Exclusion Criteria
* Cirrhosis of the liver
* Any history of hepatic decompensation including ascites, hepatic encephalopathy or variceal bleeding
* Weight reduction surgery in the past 5 years
* Positive for hepatitis C virus (HCV) RNA
* Positive for HBsAg
* Alcohol consumption greater than 21oz/week for males or 14oz/week for females
* Positive urine screen for amphetamines, cocaine or opiates (i.e. heroin, morphine) at screening.
* Clinically significant cardiac disease
* History of malignancy, other than non-melanomatous skin cancer, within 5 years prior to screening
* Major surgical procedure within 30 days prior to screening or the presence of an open wound
* 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
* BMI \< 18 kg/m\^2
18 Years
65 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
Southern California Liver Centers
Coronado, California, United States
University of California, San Diego (UCSD)
San Diego, California, United States
University of California San Francisco (UCSF)
San Francisco, California, United States
University of Colorado
Aurora, Colorado, United States
Miami Veterans Administration Healthcare System
Miami, Florida, United States
Tampa General Hospital
Tampa, Florida, United States
Northwestern University
Chicago, Illinois, 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
New Orleans, Louisiana, United States
Mercy Medical Center
Baltimore, Maryland, United States
Walter Reed National Military Medical Center
Bethesda, Maryland, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Lahey Clinic
Burlington, Massachusetts, United States
University of Michigan
Ann Arbor, Michigan, United States
Minnnesota Gastroenterology, PA
Saint Paul, Minnesota, United States
University of Mississippi Medical Center
Jackson, Mississippi, United States
Saint Louis University Hospital
St Louis, Missouri, United States
State University Of New York
Buffalo, New York, United States
Weill Cornell Medical College
New York, New York, United States
Mount Sinai Hospital
New York, New York, United States
Duke University
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
Medical University of South Carolina
Charleston, South Carolina, United States
Texas Clinical Research Institute, LLC
Arlington, Texas, United States
Brooke Army Medical Center
Fort Sam Houston, Texas, United States
St. Luke's Episcopal Hospital
Houston, Texas, United States
Alamo Clinical Research Associates
San Antonio, Texas, United States
University of Utah
Salt Lake City, Utah, United States
University of Virginia Health System
Charlottesville, Virginia, United States
Liver Institute of Virginia
Newport News, Virginia, United States
Digestive and Liver Disease Specialists
Norfolk, Virginia, United States
Bucheon St. Marys Hospital
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 Ghent
Ghent, , Belgium
University of Calgary
Calgary, Alberta, Canada
University of Manitoba
Winnipeg, Manitoba, Canada
London Health Science Center
London, Ontario, Canada
Toronto Liver Centre
Toronto, Ontario, Canada
Hopital Beaujon
Clichy, , France
Hospital Saint-Antoine
Paris, , France
Groupe Hospitalier Pitié- Salpétrière
Paris, , France
CHU Strasbourg Hôpital Civil
Strasbourg, , France
Medizinische Hochschule Hannover
Hanover, , Germany
Gastroenterologisch-Hepatologisches Zentrum Kiel
Kiel, , Germany
EUGASTRO GmbH
Leipzig, , Germany
Azienda Ospedaliero-Universitaria di Modena Policlinico
Modena, , Italy
Azienda Ospedaliera San Camillo Forlanini
Roma, , Italy
Azienda Ospedaliera Città della Salute e della Scienza di Torino
Torino, , Italy
Fundacion De Investigacion
San Juan, , Puerto Rico
Hospital Vall d'Hebron
Barcelona, , Spain
Hospital Clinic de Barcelona
Barcelona, , Spain
Hospital Donostia
Donostia / San Sebastian, , Spain
Hospital Universitario Puerta de Hierro
Majadahonda, , Spain
John Radcliffe Hospital
Headington, , United Kingdom
The Royal London Hospital
London, , United Kingdom
Royal Free Hospital, Pond Street
London, , United Kingdom
King's College Hospital NHS Foundation Trust No. 1 Account
London, , United Kingdom
Nottingham University Hospitals Queens Medica
Nottingham, , United Kingdom
Countries
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References
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Sanyal A, Harrison S, Ratziu V, Abdelmalek M, Diehl A, Caldwell S, et al. Changes in fibrosis, but not the NAFLD Activity Score (NAS), are associated with disease progression in patients with nonalcoholic steatohepatitis (NASH) and advanced fibrosis. J Hepatol 2017; 66 (1): S2.
Sanyal A, Abdelmalek M, Diehl A, Caldwell S, Shiffman M, Ghalib R, et al. Efficacy and safety of simtuzumab for the treatment of nonalcoholic steatohepatitis with bridging fibrosis or cirrhosis: results of two phase 2b, dose-ranging, randomized, placebo-controlled trials. J Hepatol 2017; 66 (1): S54.
Ratziu V, Sanyal A, Torres D, Hinrichsen H, Serfaty L, Bambha K, et al. Impact of weight reduction on serum markers and liver histology including progression to cirrhosis in patients with nonalcoholic steatohepatitis (NASH) and bridging fibrosis. J Hepatol 2017; 66 (1): S594.
Shea PR, Sanyal A, Harrison S, Ratziu V, Loomba R, Caldwell S, et al. PNPLA3 variants confer an increased risk of advanced fibrosis due to non-alcoholic steatohepatitis. J Hepatol 2016; 64 (2): S493.
Shea PR, Sanyal A, Rockey DC, Loomba R, Diehl AM, Kleinstein SE, et al. Genome-wide association study of clinically significant portal hypertension in patients with nonalcoholic steatohepatitis and advanced fibrosis. J Hepatol 2016; 64 (2): S280.
Goodman ZD, Alaparthi L, Monge F, Patel K, Loomba R, Caldwell SH, et al. Correlations between hepatic morphometric collagen content, histologic fibrosis staging, and serum markers in patients with advanced fibrosis due to nonalcoholic steatohepatitis (NASH). Hepatol 2015; 62 (1): 906A.
Harrison SA, Goodman ZD, Ratziu V, Loomba R, Diehl AM, Lawitz E, et al. Serum lysyl oxidase-like-2 (sLOXL2) levels correlate with fibrosis stage in patients with nonalcoholic steatohepatitis (NASH). Hepatol 2015; 62 (1): 910A.
Ratziu V, Sanyal AJ, Loomba R, Caldwell SH, Ghalib RH, Torres DM, et al. Characterization of insulin resistance in patients with advanced fibrosis due to nonalcoholic steatohepatitis (NASH). Hepatol 2015; 62 (1): 1298A-1299A.
Loomba R, Huang DQ, Sanyal AJ, Anstee QM, Trauner M, Lawitz EJ, Ding D, Ma L, Jia C, Billin A, Huss RS, Chung C, Goodman Z, Wong VW, Okanoue T, Romero-Gomez M, Abdelmalek MF, Muir A, Afdhal N, Bosch J, Harrison S, Younossi ZM, Myers RP. Liver stiffness thresholds to predict disease progression and clinical outcomes in bridging fibrosis and cirrhosis. Gut. 2023 Mar;72(3):581-589. doi: 10.1136/gutjnl-2022-327777. Epub 2022 Sep 9.
Younossi ZM, Anstee QM, Wai-Sun Wong V, Trauner M, Lawitz EJ, Harrison SA, Camargo M, Kersey K, Subramanian GM, Myers RP, Stepanova M. The Association of Histologic and Noninvasive Tests With Adverse Clinical and Patient-Reported Outcomes in Patients With Advanced Fibrosis Due to Nonalcoholic Steatohepatitis. Gastroenterology. 2021 Apr;160(5):1608-1619.e13. doi: 10.1053/j.gastro.2020.12.003. Epub 2020 Dec 8.
Harrison SA, Abdelmalek MF, Caldwell S, Shiffman ML, Diehl AM, Ghalib R, Lawitz EJ, Rockey DC, Schall RA, Jia C, McColgan BJ, McHutchison JG, Subramanian GM, Myers RP, Younossi Z, Ratziu V, Muir AJ, Afdhal NH, Goodman Z, Bosch J, Sanyal AJ; GS-US-321-0105 and GS-US-321-0106 Investigators. Simtuzumab Is Ineffective for Patients With Bridging Fibrosis or Compensated Cirrhosis Caused by Nonalcoholic Steatohepatitis. Gastroenterology. 2018 Oct;155(4):1140-1153. doi: 10.1053/j.gastro.2018.07.006. Epub 2018 Jul 7.
Other Identifiers
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2012-002488-88
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
GS-US-321-0105
Identifier Type: -
Identifier Source: org_study_id
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