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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Gilead Sciences
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01672853
First received: August 22, 2012
Last updated: June 8, 2014
Last verified: June 2014
  Purpose

The purpose of this study is to evaluate whether Simtuzumab (GS-6624) is effective at preventing the progression of liver fibrosis in subjects with PSC.


Condition Intervention Phase
Primary Sclerosing Cholangitis (PSC)
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, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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 Primary Sclerosing Cholangitis (PSC)

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Change from baseline in morphometric quantitative collagen on liver biopsy [ Time Frame: Week 96 ] [ Designated as safety issue: No ]

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: February 2013
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Arm A
Subject will receive subcutaneous injections of 75 mg of Simtuzumab (GS-6624) weekly for 96 weeks.
Biological: Simtuzumab
Other Name: GS-6624
Experimental: Treatment Arm B
Subject will receive subcutaneous injections of 125 mg of Simtuzumab (GS-6624) weekly for 96 weeks.
Biological: Simtuzumab
Other Name: GS-6624
Placebo Comparator: Treatment Arm C
Subject will receive subcutaneous injections of placebo weekly for 96 weeks.
Biological: Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult subjects (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 subjects with PSC may have a normal liver biopsy, in the event of a normal liver biopsy, the subject must have an abnormal magnetic resonance cholangiopancreatography (MRCP).
  • MRCP consistent with PSC: Some subjects with PSC may have a normal MRCP; in the event of a normal MRCP, the subject 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 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 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
  • 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 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. 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 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 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: NCT01672853

Contacts
Contact: Linda Huynh Linda.Huynh@gilead.com

  Show 76 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Jeffrey Bornstein, M.D. Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01672853     History of Changes
Other Study ID Numbers: GS-US-321-0102, 2012-002473-61
Study First Received: August 22, 2012
Last Updated: June 8, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
Primary sclerosing cholangitis
PSC
Sclerosis
Monoclonal antibody
LOXL2
Simtuzumab
Liver fibrosis
Liver disease
MRCP
MRE
Liver biopsy

Additional relevant MeSH terms:
Cholangitis
Cholangitis, Sclerosing
Liver Cirrhosis
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Liver Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 31, 2014