Simtuzumab (SIM, GS-6624) in the Treatment of Cirrhosis Due to NASH (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 2 (LOXL2), in Subjects With Compensated Cirrhosis Secondary to Non-Alcoholic Steatohepatitis (NASH)

The primary objective of this study is to evaluate the safety and efficacy of SIM (formerly referred to as 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)

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

259

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

  • Canada
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3E 3P4
        • University of Manitoba
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 2Y9
        • Dalhousie University
    • Ontario
      • Toronto, Ontario, Canada, M6H 3M1
        • Toronto Liver Centre
  • France
      • Lyon, France, 69317
        • Hôpital de la Croix Rousse
      • Paris, France, 75012
        • Hospital Saint-Antoine
      • Paris, France, 75013
        • CHU Pitié-Salpêtrière
      • Strasbourg, France, 67091
        • Fonds de Recherche Honoraires
  • Germany
      • Kiel, Germany, 24146
        • Gastroenterologisch-Hepatologisches Zentrum Kiel
      • Leipzig, Germany, 4129
        • EUGASTRO GmbH
  • Italy
      • Modena, Italy, 41100
        • Azienda Ospedaliero-Universitaria Policlinico di Modena
      • Torino, Italy, 10126
        • Azienda Ospedaliera Città della Salute e della Scienza di Torino
    • Milano
      • Rozzano, Milano, Italy, 20089
        • Istituto Clinico Humanitas
  • Puerto Rico
      • San Juan, Puerto Rico, 00927
        • Fundacion de Investigacion
  • Spain
    • Cataluna
      • Barcelona, Cataluna, Spain, 08035
        • Hospital Vall D´Hebron
    • Madrid
      • Majadahonda, Madrid, Spain, 28222
        • Hospital Universitario Puerta de Hierro
  • United Kingdom
      • London, United Kingdom, NW3 2QG
        • Royal Free Hospital, Pond Street
      • London, United Kingdom, SE5 9RS
        • King's College Hospital NHS Trust
      • Nottingham, United Kingdom, NG7 2UH
        • Nottingham University Hospitals Queen's Medical Centre
  • 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, Denver
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami
      • Tampa, Florida, United States, 33606
        • Tampa General Hospital
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University School of Medicine, Division of Gastroenterology/Hepatology
    • 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
      • Burlington, Massachusetts, United States, 01805
        • Lahey Clinic
    • Michigan
      • Jackson, Michigan, United States, 39216
        • University of Mississippi Medical Center
    • Minnesota
      • Saint Paul, Minnesota, United States, 55114
        • Minnnesota Gastroenterology, PA
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Saint Louis University Hospital
    • New York
      • Buffalo, New York, United States, 14203
        • State University of New York at Buffalo
      • Manhasset, New York, United States, 11030
        • North Shore University Health System
      • New York, New York, United States, 10032
        • Columbia University Medical Center
      • New York, New York, United States, 10016
        • New York University
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • University Hospitals Case Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania Hospital
    • Rhode Island
      • Providence, Rhode Island, United States, 02905
        • University Gastroenterology
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
    • Tennessee
      • Memphis, Tennessee, United States, 38104
        • Methodist University Hospital
      • Nashville, Tennessee, United States, 37212
        • Vanderbilt University Medical Center
    • Texas
      • Arlington, Texas, United States, 76012
        • Texas Clinical Research Institute
      • Fort Sam Houston, Texas, United States, 78234
        • Brooke Army Medical Center
      • Houston, Texas, United States, 77030
        • St. Luke Episcopal Hospital
      • San Antonio, Texas, United States, 78215
        • Alamo Clinical Research Associates
    • Utah
      • Murray, Utah, United States, 84107
        • Intermountain Transplant Center
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Health Center
      • 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
      • Richmond, Virginia, United States, 23226
        • 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 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
  • The liver biopsy sample must be determined to be adequate for evaluation by the Central pathologist
  • 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

Key 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 year
  • Child-Pugh-Turcotte (CPT) score >7; Model for End-Stage Liver Disease (MELD) score > 12 and Body Mass Index (BMI) <18kg/m2
  • 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
  • History of solid-organ transplant; poor venous access or requirement for permanent or semi-permanent central vein catheter such as portacath

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: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: SIM 200 mg
During the Randomized Double-Blind Phase, participants will receive SIM 200 mg via intravenous infusion every 2 weeks for up to 240 weeks. During the optional Open-Label Phase, participants will receive SIM 700 mg via intravenous infusion every 2 weeks for up to an additional 240 weeks.
Biological: SIM
Intravenous infusion over 30 minutes every 2 weeks
Other Names:
  • GS-6624
Experimental: SIM 700 mg
During the Randomized Double-Blind Phase, participants will receive SIM 700 mg via intravenous infusion every 2 weeks for up to 240 weeks. During the optional Open-Label Phase, participants will receive SIM 700 mg via intravenous infusion every 2 weeks for up to an additional 240 weeks.
Biological: SIM
Intravenous infusion over 30 minutes every 2 weeks
Other Names:
  • GS-6624
Placebo Comparator: Placebo
During the Randomized Double-Blind Phase, participants will receive placebo to match SIM administered via intravenous infusion every 2 weeks for up to 240 weeks. During the optional Open-Label Phase, participants will receive SIM 700 mg administered via intravenous infusion every 2 weeks for up to an additional 240 weeks.
Biological: SIM
Intravenous infusion over 30 minutes every 2 weeks
Other Names:
  • GS-6624
Biological: Placebo
Placebo to match SIM intravenous infusion over 30 minutes every 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Hepatic Venous Pressure Gradient (HVPG)
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 clinical event or last dose date (maximum: 240 weeks in Blinded Phase); which ever occurred first

Event free survival (EFS) was the primary clinical efficacy endpoint and was assessed by time to first liver-related event or death, whichever occurs first. Liver-related events included 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
Baseline up to the time of clinical event or last dose date (maximum: 240 weeks in 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)

October 29, 2012

Primary Completion (Actual)

September 26, 2016

Study Completion (Actual)

January 3, 2017

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-321-0106
  • 2012-002489-11 (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

product manufactured in and exported from the U.S.

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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