Simtuzumab (GS-6624) in the Treatment of Cirrhosis Due to NASH

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01672879
First received: August 22, 2012
Last updated: August 6, 2014
Last verified: August 2014
  Purpose

This study is to evaluate the safety and efficacy of simtuzumab (GS-6624) in adults with compensated cirrhosis due to Non-Alcoholic Steatohepatitis (NASH). It will consist of 2 phases:

  • Randomized Double-Blind Phase
  • Open Label Phase (optional)

Condition Intervention Phase
Non-Alcoholic Steatohepatitis (NASH)
Biological: Simtuzumab
Biological: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2b, Dose-Ranging, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Safety and Efficacy of GS-6624, a Monoclonal Antibody Against Lysyl Oxidase-Like 2 (LOXL2), in Subjects With Compensated Cirrhosis Secondary to Non-Alcoholic Steatohepatitis (NASH)

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Mean change from baseline in hepatic venous pressure gradient (HVPG) [ Time Frame: Baseline to Week 96 ] [ Designated as safety issue: No ]
  • Event free survival [ Time Frame: Up to 240 weeks ] [ Designated as safety issue: No ]

    Event free survival (EFS) will be assessed by time to first liver-related event or death, whichever occurs first. Liver-related events include any of the following:

    • Liver transplantation
    • Qualification for liver transplantation

      -- Model for End-Stage Liver Disease (MELD) ≥ 15

    • Events indicative of hepatic decompensation

      • Esophageal variceal bleeding
      • Ascites
      • Hepatic Encephalopathy
      • ≥ 2 point increase in Child Pugh-Turcotte (CPT) score
      • Newly diagnosed varices in a subject without prior varices


Secondary Outcome Measures:
  • Safety data including adverse events, extent of exposure, laboratory evaluations, and immunogenicity [ Time Frame: Baseline to Week 96 plus 30 days ] [ Designated as safety issue: No ]
    Safety data collected will be summarized by treatment arm.


Estimated Enrollment: 225
Study Start Date: October 2012
Estimated Study Completion Date: November 2022
Estimated Primary Completion Date: April 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Arm A
Participants will receive simtuzumab 700 mg for up to 240 weeks during the Randomized Phase. During the optional Open Label Phase, participants will receive simtuzumab 700 mg for up to an additional 240 weeks.
Biological: Simtuzumab
Simtuzumab administered by intravenous infusion over 30 minutes every 2 weeks
Other Name: GS-6624
Experimental: Treatment Arm B
Participants will receive simtuzumab 200 mg for up to 240 weeks during the Randomized Phase. During the optional Open Label Phase, participants will receive simtuzumab 700 mg for up to an additional 240 weeks.
Biological: Simtuzumab
Simtuzumab administered by intravenous infusion over 30 minutes every 2 weeks
Other Name: GS-6624
Placebo Comparator: Treatment Arm C
Participants will receive placebo to match simtuzumab for up to 240 weeks during the Randomized Phase. During the optional Open Label Phase, participants will receive simtuzumab 700 mg for up to an additional 240 weeks.
Biological: Placebo
Placebo to match simtuzumab administered by intravenous infusion over 30 minutes every 2 weeks

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult subjects (aged 18-65) with cirrhosis of the liver defined as an Ishak fibrosis stage ≥ 5
  • Liver biopsy consistent with NASH or cryptogenic cirrhosis
  • 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 the upper limit of the normal range (ULN)
  • Must have serum creatinine < 2.0 mg/dL
  • A negative serum pregnancy test is required for female subjects of childbearing potential
  • All sexually active female subjects 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
  • Male subjects, 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:

  • Pregnant or breast feeding
  • 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. Subjects on stable methadone or buprenorphine maintenance treatment for at least 6 months prior to screening may be included in the study. Subjects 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 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 subject's compliance with the protocol procedures;
  • Participation in an investigational trial of a drug or device within 30 days prior to screening
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01672879

  Hide Study Locations
Locations
United States, Arizona
Mayo Clinic Hospital
Phoenix, Arizona, United States, 85054
United States, California
Southern California Liver Centers
Coronado, California, United States, 92118
VA Greater Los Angeles Healthcare System
Los Angeles, California, United States, 90073
Veterans Affairs Palo Alto Health Care System
Palo Alto, California, United States, 94304
University of California, San Diego Medical Center
San Diego, California, United States, 92103
University of California San Francisco
San Francisco, California, United States, 94143
United States, Colorado
University of Colorado, Denver
Aurora, Colorado, United States, 80045
United States, Florida
University of Miami Center for Liver Diseases
Miami, Florida, United States, 33136
Miami Veterans Administration Healthcare System
Miami, Florida, United States, 33125
Florida Hospital Transplant Center
Orlando, Florida, United States, 32804
Tampa General Hospital
Tampa, Florida, United States, 33606
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60707
United States, Indiana
Indiana University School of Medicine, Division of Gastroenterology/Hepatology
Indianapolis, Indiana, United States, 46202
United States, Iowa
Iowa Digestive Disease Center
Clive, Iowa, United States, 50325
United States, Kentucky
University of Louisville
Louisville, Kentucky, United States, 40202
United States, Louisiana
Tulane University Health Sciences Center
New Orleans, Louisiana, United States, 70112
United States, Maryland
Mercy Medical Center
Baltimore, Maryland, United States, 21202
Walter Reed National Military Medical Center
Bethesda, Maryland, United States, 20889
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Lahey Clinic
Burlington, Massachusetts, United States, 01805
United States, Michigan
University of Mississippi Medical Center
Jackson, Michigan, United States, 39216
United States, Minnesota
Minnnesota Gastroenterology, PA
St. Paul, Minnesota, United States, 55114
United States, Missouri
Kansas City VA Medical Center
Kansas City, Missouri, United States, 64110
Saint Louis University
St. Louis, Missouri, United States, 63104
United States, New York
State University Of New York
Buffalo, New York, United States, 14230
North Shore University
Manhasset, New York, United States, 11030
New York University
New York, New York, United States, 10016
Mount Sinai Hospital
New York, New York, United States, 10029
Columbia University Medical Center
New York, New York, United States, 10032
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
University Hospitals Case Medical Center
Cleveland, Ohio, United States, 44106
United States, Oklahoma
Oklahoma Gastroenterology Associates
Tulsa, Oklahoma, United States, 74104
Options Health Research
Tulsa, Oklahoma, United States, 74104
United States, Pennsylvania
University of Pennsylvania Hospital
Philadelphia, Pennsylvania, United States, 19104
United States, Rhode Island
University Gastroenterology
Providence, Rhode Island, United States, 02905
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29542
United States, Tennessee
Methodist University Hospital
Memphis, Tennessee, United States, 38104
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37212
United States, Texas
Texas Clinical Research Institute, LLC
Arlington, Texas, United States, 76012
Brooke Army Medical Center
Fort Sam Houston, Texas, United States, 78234
St. Luke Episcopal Hospital
Houston, Texas, United States, 77030
Texas Liver Institute, Inc.
San Antonio, Texas, United States, 78215
United States, Utah
Intermountain Medical Center
Murray, Utah, United States, 84157
University of Utah
Salt Lake City, Utah, United States, 84132
United States, Virginia
University of Virginia Health Center
Charlottesville, Virginia, United States, 22908
Liver Institute of Virginia
Newport News, Virginia, United States, 23603
Digestive and Liver Disease Specialists
Norfolk, Virginia, United States, 23502
Virginia Commonwealth University Health System
Richmond, Virginia, United States, 23298
Bucheon St. Marys Hospital
Richmond, Virginia, United States, 23603
United States, Washington
Virginia Mason Medical Center
Seattle, Washington, United States, 98101
University of Washington
Seattle, Washington, United States, 98103
Canada, Manitoba
University of Manitoba
Winnipeg, Manitoba, Canada, R3E 3P4
Canada, Nova Scotia
Dalhousie University
Halifax, Nova Scotia, Canada, B3H 2Y9
Canada, Ontario
Toronto Liver Centre
Toronto, Ontario, Canada, M6H 3M1
Toronto Western Hospital
Toronto, Ontario, Canada, M5T 2S8
France
Hopital Beaujon
Clichy, France, 92118
Groupe Hospitalier Pitié- Salpétrière
Paris, France, 75013
Hospital Saint-Antoine
Paris, France, 75012
Germany
Universitätsklinikum Frankfurt
Frankfurt, Germany, 60590
Medizinische Hochschule Hannover
Hannover, Germany, 30625
Gastroenterologisch-Hepatologisches Zentrum Kiel
Kiel, Germany, 24146
Klinikum St. George gGmbH
Leipzig, Germany, 4129
Italy
Istituto Clinico Humanitas
Rozzano, Milano, Italy, 20089
Azienda Ospedaliero-Universitaria di Modena Policlinico
Modena, Italy, 41100
Azienda Ospedaliera San Camillo Forlanini
Roma, Italy, 144
Azienda Ospedaliera Città della Salute e della Scienza di Torino
Torino, Italy, 10126
Puerto Rico
Fundacion De Investigacion De Diego
San Juan, Puerto Rico, 927
Spain
Hospital Vall D´Hebron
Barcelona, Cataluna, Spain, 8035
Hospital Clinic de Barcelona
Barcelona, Cataluña, Spain, 8036
Hospital Universitario Puerta de Hierro
Majadahonda, Madrid, Spain, 28222
Hospital Donostia
San Sebastian, Spain, 20080
United Kingdom
Imperial College Healthcare NHS Trust- St. Mary's Hospital
London, United Kingdom, W2 1NY
University College London
London, United Kingdom, WC1E 6HX
King's College Hospital
London, United Kingdom, SE5 9RS
Queen's Medical Centre
Nottingham, United Kingdom, NG7 2UH
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Jeffrey Bornstein, MD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01672879     History of Changes
Other Study ID Numbers: GS-US-321-0106, 2012-002489-11
Study First Received: August 22, 2012
Last Updated: August 6, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
NASH
cirrhosis
Compensated Liver disease
Monoclonal antibody
LOXL2
Simtuzumab
Nonalcoholic Steatohepatitis
Hepatic venous pressure gradient
HVPG
NAFLD
MRE
Liver biopsy

Additional relevant MeSH terms:
Fatty Liver
Liver Diseases
Digestive System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014