Simtuzumab (GS-6624) in the Treatment of Liver Fibrosis in Subjects With Advanced Liver Fibrosis But Not Cirrhosis Secondary to Non-Alcoholic Steatohepatitis (NASH)

This study is currently recruiting participants.
Verified March 2014 by Gilead Sciences
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01672866
First received: August 22, 2012
Last updated: March 24, 2014
Last verified: March 2014
  Purpose

The purpose of the study is to evaluate whether Simtuzumab (GS-6624) is effective in treating liver fibrosis in subjects with Advanced Liver Fibrosis but not Cirrhosis Secondary to Non-Alcoholic Steatohepatitis (NASH)


Condition Intervention Phase
Non-Alcoholic Steatohepatitis (NASH)
Biological: Simtuzumab 75 mg
Biological: Simtuzumab 125 mg
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: 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 Molecule 2 (LOXL2) in Subjects With Advanced Liver Fibrosis But Not Cirrhosis Secondary to Non-Alcoholic Steatohepatitis (NASH)

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: December 2012
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
Subjects will receive subcutaneous injections of Simtuzumab (GS-6624) 75mg once weekly for 96 weeks.
Biological: Simtuzumab 75 mg
The Simtuzumab (GS-6624) is administered by subcutaneous injection weekly
Other Name: GS-6624
Experimental: Treatment Arm B
Subjects will receive subcutaneous injections of Simtuzumab (GS-6624) 125mg once weekly for 96 weeks.
Biological: Simtuzumab 125 mg
The Simtuzumab (GS-6624) is administered by subcutaneous injection weekly
Other Name: GS-6624
Placebo Comparator: Treatment Arm C
Subjects will receive subcutaneous injections of placebo of GS-6624 once weekly for 96 weeks
Biological: Placebo
The placebo to match Simtuzumab (GS-6624) is administered by subcutaneous injection weekly

  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 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 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 must refrain from sperm donation from Day 0 throughout the study period and for a period of 90 days following the last dose of study drug

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 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01672866

Contacts
Contact: Jeannine Madere Jeannine.Madere@gilead.com

  Show 92 Study Locations
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: NCT01672866     History of Changes
Other Study ID Numbers: GS-US-321-0105, 2012-002488-88
Study First Received: August 22, 2012
Last Updated: March 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
NASH
non cirrhotic
Monoclonal antibody
LOXL2
Simtuzumab
Nonalcoholic Steatohepatitis
NAFLD
Liver biopsy
MRE

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

ClinicalTrials.gov processed this record on April 21, 2014