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 ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01672866
First received: August 22, 2012
Last updated: August 15, 2014
Last verified: August 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
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: NCT01672866

  Show 91 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: August 15, 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:
Fatty Liver
Fibrosis
Digestive System Diseases
Liver Diseases
Pathologic Processes
Antibodies, Monoclonal
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 21, 2014