Simtuzumab (GS-6624) in the Prevention of Progression of Liver Fibrosis in Adults With Primary Sclerosing Cholangitis (PSC)

Phase 2

Completed

Conditions: Primary Sclerosing Cholangitis (PSC)

Interventions: Biological: Simtuzumab
Biological: Placebo

Registration Number: NCT01672853

Lead Sponsor: Gilead Sciences

Brief Summary: The purpose of this study is to evaluate whether simtuzumab (GS-6624) is effective at preventing the progression of liver fibrosis in adults with primary sclerosing cholangitis (PSC).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 235

Inclusion Criteria

Adult Individuals (aged 18-70) with chronic cholestatic liver disease of at least 6 months.
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

Key

Exclusion Criteria

Pregnant or breast feeding
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

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment Arm A	Simtuzumab	Simtuzumab 75 mg for 96 weeks
Treatment Arm C	Placebo	Placebo for 96 weeks
Treatment Arm B	Simtuzumab	Simtuzumab 125 mg for 96 weeks

Primary Outcome Measures

Name	Time	Method
Change From Baseline in MQC on Liver Biopsy at Week 96	Baseline; Week 96

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event	First dose date up to Week 96
Study Drug Exposure	First dose date up to Week 96	The average SIM exposure was summarized.
Percentage of Participants Experiencing Any Treatment-Emergent Laboratory Abnormality	First dose date up to Week 96 plus 30 days	A treatment-emergent graded laboratory abnormality was defined as an increase of at least 1 abnormality grade from the predose assessment and occurring after the predose visit and on or before the date of the administration of study drug plus 30 days. The most severe graded abnormality from all tests was counted for each participant \[Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe); Grade 4 (life-threatening)\].

Trial Locations

Locations (75): 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
Verterans Adminstration Hospital
🇺🇸
Palo Alto, California, United States
Scripps Clinic
🇺🇸
La Jolla, California, United States
Tulane University Health Sciences Center
🇺🇸
New Orleans, Louisiana, United States
Minnesota Gastroenterology, PA
🇺🇸
Saint Paul, Minnesota, United States
University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
Mount Sinai Hospital
🇺🇸
New York, New York, United States
University Gastroenterology
🇺🇸
Providence, Rhode Island, United States
Brooke Army Medical Center
🇺🇸
Fort Sam Houston, Texas, United States
UT Southwestern Medical Center
🇺🇸
Dallas, Texas, United States
Intermountain Medical Center
🇺🇸
Murray, 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
UZ Antwerpen
🇧🇪
Edegem, Belgium
UZ Gent
🇧🇪
Gent, Belgium
London Health Science Center
🇨🇦
London, Ontario, Canada
Dalhousie University
🇨🇦
Halifax, Nova Scotia, Canada
Toronto Liver Centre
🇨🇦
Toronto, Ontario, Canada
University of Manitoba
🇨🇦
Winnepeg, Manitoba, Canada
Hvidovre Hospital
🇩🇰
Hvidovre, Denmark
Medizinische Hochschule Hannover
🇩🇪
Hannover, Germany
Istituto Clinico Humanitas
🇮🇹
Rozzano, Milano, Italy
EUGASTRO GmbH
🇩🇪
Leipzig, Germany
Klinikum der Johann Wolfgang Goethe Universitat
🇩🇪
Frankfurt, Germany
Gastroenterologisch Hepatologisches Zentrum Kiel
🇩🇪
Kiel, Germany
Azienda Ospedaliera San Camillo Forlanini
🇮🇹
Roma, Italy
Hospital Universitario Vall d'Hebron
🇪🇸
Barcelona, Cataluna, Spain
Hospital Universitario Puerta de Hierro
🇪🇸
Majadahonda, Spain
Imperial College Healthcare NHS Trust- St. Mary's Hospital
🇬🇧
London, United Kingdom
Norfolk and Norwich University Hospital
🇬🇧
Norwich, United Kingdom
Rigshospitalet
🇩🇰
Kobenhavn O, Denmark
Århus Universitetshospital, Århus Sygehus
🇩🇰
Århus C, Denmark
University College London
🇬🇧
London, United Kingdom
John Radcliffe Hospital
🇬🇧
Headington, United Kingdom
University of Calgary
🇨🇦
Calgary, Alberta, Canada
University of Alberta
🇨🇦
Edmonton, Alberta, Canada
UZ Leuven
🇧🇪
Leuven, Belgium
Azienda Ospedaliera Città della Salute e della Scienza di Torino
🇮🇹
Torino, Italy
Eramus MC
🇳🇱
Rotterdam, Netherlands
Avd för invärtesmedicin och klinisk nutrition
🇸🇪
Goteborg, Sweden
Hospital Donostia
🇪🇸
San Sebastian, Spain
New Queen Elizabeth Hospital
🇬🇧
Birmingham, United Kingdom
Weill Cornell Medical College
🇺🇸
New York, New York, United States
Iowa Digestive Disease Center
🇺🇸
Clive, Iowa, United States
St. Louis University
🇺🇸
Saint Louis, Missouri, United States
UC Davis Medical Center
🇺🇸
Sacramento, California, United States
University of Miami Center for Liver Diseases
🇺🇸
Miami, Florida, United States
University of Louisville
🇺🇸
Louisville, Kentucky, 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
Duke Clinical Research Institute
🇺🇸
Durham, North Carolina, United States
Virginia Mason Medical Center
🇺🇸
Seattle, Washington, United States
Mayo Clinic Hospital
🇺🇸
Phoenix, Arizona, United States
University of California San Francisco
🇺🇸
San Francisco, California, United States
University of Colorado Denver
🇺🇸
Aurora, Colorado, United States
Northwestern University
🇺🇸
Chicago, Illinois, United States
Indiana University
🇺🇸
Indianapolis, Indiana, United States
University of San Diego Medical Center
🇺🇸
San Diego, California, United States
Indianapolis Gastroenterology Research Foundation
🇺🇸
Indianapolis, Indiana, United States
University Hospitals Case Medical Center
🇺🇸
Cleveland, Ohio, United States
Cleveland Clinic
🇺🇸
Cleveland, Ohio, United States
University of Utah
🇺🇸
Salt Lake City, Utah, United States
Vanderbilt University Medical Center
🇺🇸
Nashville, Tennessee, United States
Alamo Medical Research
🇺🇸
San Antonio, Texas, United States
St. Luke Episcopal Hospital
🇺🇸
Houston, Texas, United States
University of Washington
🇺🇸
Seattle, Washington, United States
Université Catholique de Louvain
🇧🇪
Bruxelles, Belgium
Hôpital Erasme
🇧🇪
Brussels, Belgium
University of Nottingham
🇬🇧
Nottingham, United Kingdom