Safety and Efficacy of Simtuzumab (SIM, GS-6624) in Adults With Advanced Liver Fibrosis But Not Cirrhosis Secondary to Non-Alcoholic Steatohepatitis (NASH)

March 1, 2019 updated by: Gilead Sciences

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 Molecule 2 (LOXL2), in Subjects With Advanced Liver Fibrosis But Not Cirrhosis Secondary to Non-Alcoholic Steatohepatitis (NASH)

The primary objective of this study is to evaluate whether SIM (formerly referred to as GS-6624) is effective at preventing the histologic progression of liver fibrosis and the clinical progression to cirrhosis in participants with NASH.

It will consist of 2 phases:

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

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

222

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brussels, Belgium, 1070
        • Hôpital Erasme
      • Bruxelles, Belgium, 1200
        • Université Catholique de Louvain
      • Gent, Belgium, B-9000
        • UZ Ghent
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4Z6
        • University of Calgary
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3E 3P4
        • University of Manitoba
    • Ontario
      • London, Ontario, Canada, N6A 5A5
        • London Health Science Center
      • Toronto, Ontario, Canada, M6H 3M1
        • Toronto Liver Centre
  • France
      • Clichy, France, 92110
        • Hôpital Beaujon
      • Paris, France, 75012
        • Hospital Saint-Antoine
      • Paris, France, 75013
        • Groupe Hospitalier Pitié- Salpétrière
      • Strasbourg, France, 67091
        • CHU Strasbourg Hôpital Civil
  • Germany
      • Hannover, Germany, 30625
        • Medizinische Hochschule Hannover
      • Kiel, Germany, 24146
        • Gastroenterologisch-Hepatologisches Zentrum Kiel
      • Leipzig, Germany, 4103
        • Eugastro GmbH
  • Italy
      • Modena, Italy, 41100
        • Azienda Ospedaliero-Universitaria di Modena Policlinico
      • Roma, Italy, 152
        • Azienda Ospedaliera San Camillo Forlanini
      • Torino, Italy, 10126
        • Azienda Ospedaliera Città della Salute e della Scienza di Torino
  • Puerto Rico
      • San Juan, Puerto Rico, 00927
        • Fundacion de Investigacion
  • Spain
      • Barcelona, Spain, 08036
        • Hospital Clinic De Barcelona
      • Barcelona, Spain, 08035
        • Hospital Vall d'Hebron
      • Majadahonda, Spain, 28222
        • Hospital Universitario Puerta de Hierro
      • San Sebastian, Spain, 20080
        • Hospital Donostia
  • United Kingdom
      • Headington, United Kingdom, OX3 9DU
        • John Radcliffe Hospital
      • London, United Kingdom, NW3 2QG
        • Royal Free Hospital, Pond Street
      • London, United Kingdom, E1 1BB
        • The Royal London Hospital
      • London, United Kingdom, SE5 9RS
        • King's College Hospital NHS Foundation Trust No. 1 Account
      • Nottingham, United Kingdom, NG7 2UH
        • Nottingham University Hospitals Queens Medica
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic Hospital
    • California
      • Coronado, California, United States, 92118
        • Southern California Liver Centers
      • San Diego, California, United States, 92103
        • University of California, San Diego (UCSD)
      • San Francisco, California, United States, 94143
        • University of California San Francisco (UCSF)
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado
    • Florida
      • Miami, Florida, United States, 33136
        • Miami Veterans Administration HealthCare System
      • Tampa, Florida, United States, 33606
        • Tampa General Hospital
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
    • Indiana
      • Indianapolis, Indiana, United States, 46237
        • Indianapolis Gastroenterology Research Foundation
    • Iowa
      • Clive, Iowa, United States, 50325
        • Iowa Digestive Disease Center
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • University of Louisville
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Tulane University
    • Maryland
      • Baltimore, Maryland, United States, 21202
        • Mercy Medical Center
      • Bethesda, Maryland, United States, 20889
        • Walter Reed National Military Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Burlington, Massachusetts, United States, 01805
        • Lahey Clinic
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan
    • Minnesota
      • Saint Paul, Minnesota, United States, 55114
        • Minnnesota Gastroenterology, PA
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • University of Mississippi Medical Center
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Saint Louis University Hospital
    • New York
      • Buffalo, New York, United States, 14203
        • State University of New York
      • New York, New York, United States, 10029
        • Mount Sinai Hospital
      • New York, New York, United States, 10021
        • Weill Cornell Medical College
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic
      • Cleveland, Ohio, United States, 44106
        • University Hospitals Case Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
    • Rhode Island
      • Providence, Rhode Island, United States, 02905
        • University Gastroenterology
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
    • Texas
      • Arlington, Texas, United States, 76012
        • Texas Clinical Research Institute, LLC
      • Fort Sam Houston, Texas, United States, 78234
        • Brooke Army Medical Center
      • Houston, Texas, United States, 77030
        • St. Luke's Episcopal Hospital
      • San Antonio, Texas, United States, 78215
        • Alamo Clinical Research Associates
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Health System
      • Newport News, Virginia, United States, 23602
        • Liver Institute of Virginia
      • Norfolk, Virginia, United States, 23502
        • Digestive and Liver Disease Specialists
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University Health System
      • Richmond, Virginia, United States, 23229
        • Bucheon St. Marys Hospital
    • Washington
      • Seattle, Washington, United States, 98101
        • Virginia Mason Medical Center
      • Seattle, Washington, United States, 98104
        • University of Washington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Key Inclusion Criteria:

  • Adults with chronic liver disease due to NASH defined as macrovesicular steatosis involving > 5% of hepatocytes on a liver biopsy with associated lobular inflammation
  • 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.

Key Exclusion Criteria:

  • Pregnant or breast feeding
  • 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

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Biological: SIM
Subcutaneous injection every week
Other Names:
  • GS-6624
Experimental: 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.
Biological: SIM
Subcutaneous injection every week
Other Names:
  • GS-6624
Placebo Comparator: 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.
Biological: SIM
Subcutaneous injection every week
Other Names:
  • GS-6624
Biological: Placebo
Placebo to match SIM via subcutaneous injection every week

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in MQC on Liver Biopsy
Time Frame: Baseline to Week 96
Baseline to Week 96
Event Free Survival (EFS) Using Kaplan-Meier
Time Frame: Baseline up to the time of progression to cirrhosis or last dose date (maximum: 240 weeks in the Blinded Phase), which ever occurred first
The EFS was the primary clinical efficacy endpoint and was assessed by the time to progression to cirrhosis. Participants were considered to have become cirrhotic if they had a post-baseline biopsy consistent with cirrhosis or developed overt signs and symptoms of cirrhosis. All overt signs and symptoms went through an adjudication process and were confirmed before they were considered for the EFS analysis.
Baseline up to the time of progression to cirrhosis or last dose date (maximum: 240 weeks in the Blinded Phase), which ever occurred first

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gilead Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 5, 2012

Primary Completion (Actual)

August 2, 2016

Study Completion (Actual)

December 29, 2016

Study Registration Dates

First Submitted

August 22, 2012

First Submitted That Met QC Criteria

August 22, 2012

First Posted (Estimate)

August 27, 2012

Study Record Updates

Last Update Posted (Actual)

March 27, 2019

Last Update Submitted That Met QC Criteria

March 1, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GS-US-321-0105
  • 2012-002488-88 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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