Simtuzumab (GS-6624) in the Treatment of Cirrhosis Due to NASH

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01672879
First received: August 22, 2012
Last updated: August 6, 2014
Last verified: August 2014
  Purpose

This study is to evaluate the safety and efficacy of simtuzumab (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)

Condition Intervention Phase
Non-Alcoholic Steatohepatitis (NASH)
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, Caregiver, 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 2 (LOXL2), in Subjects With Compensated Cirrhosis Secondary to Non-Alcoholic Steatohepatitis (NASH)

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Mean change from baseline in hepatic venous pressure gradient (HVPG) [ Time Frame: Baseline to Week 96 ] [ Designated as safety issue: No ]
  • Event free survival [ Time Frame: Up to 240 weeks ] [ Designated as safety issue: No ]

    Event free survival (EFS) will be assessed by time to first liver-related event or death, whichever occurs first. Liver-related events include 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


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: October 2012
Estimated Study Completion Date: November 2022
Estimated Primary Completion Date: April 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Arm A
Participants will receive simtuzumab 700 mg for up to 240 weeks during the Randomized Phase. During the optional Open Label Phase, participants will receive simtuzumab 700 mg for up to an additional 240 weeks.
Biological: Simtuzumab
Simtuzumab administered by intravenous infusion over 30 minutes every 2 weeks
Other Name: GS-6624
Experimental: Treatment Arm B
Participants will receive simtuzumab 200 mg for up to 240 weeks during the Randomized Phase. During the optional Open Label Phase, participants will receive simtuzumab 700 mg for up to an additional 240 weeks.
Biological: Simtuzumab
Simtuzumab administered by intravenous infusion over 30 minutes every 2 weeks
Other Name: GS-6624
Placebo Comparator: Treatment Arm C
Participants will receive placebo to match simtuzumab for up to 240 weeks during the Randomized Phase. During the optional Open Label Phase, participants will receive simtuzumab 700 mg for up to an additional 240 weeks.
Biological: Placebo
Placebo to match simtuzumab administered by intravenous infusion over 30 minutes every 2 weeks

  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 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
  • 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

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 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. 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
  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: NCT01672879

  Show 75 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: NCT01672879     History of Changes
Other Study ID Numbers: GS-US-321-0106, 2012-002489-11
Study First Received: August 22, 2012
Last Updated: August 6, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
NASH
cirrhosis
Compensated Liver disease
Monoclonal antibody
LOXL2
Simtuzumab
Nonalcoholic Steatohepatitis
Hepatic venous pressure gradient
HVPG
NAFLD
MRE
Liver biopsy

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

ClinicalTrials.gov processed this record on September 29, 2014