Safety, Tolerability, and Efficacy of GS-4997 Alone or in Combination With Simtuzumab (SIM) in Adults With Nonalcoholic Steatohepatitis (NASH) and Fibrosis Stages F2-F3

May 31, 2019 updated by: Gilead Sciences

A Phase 2, Randomized, Open Label Study Evaluating the Safety, Tolerability, and Efficacy of GS-4997 Alone or in Combination With Simtuzumab (SIM) in Subjects With Nonalcoholic Steatohepatitis (NASH) and Fibrosis Stages F2-F3

The primary objective of this study is to evaluate the safety and tolerability of GS-4997 (selonsertib [SEL]) alone or in combination with simtuzumab (SIM) in adults with nonalcoholic steatohepatitis (NASH) and fibrosis stages F2-F3. Participants will be randomized in a 2:2:1:1:1 ratio to 1 of 5 study treatment arms.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
72

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N4Z6
        • University of Calgary
    • Ontario
      • Toronto, Ontario, Canada, M6H 3M1
        • Toronto Liver Centre
  • United States
    • California
      • Palo Alto, California, United States, 94304
        • Stanford University Medical Center
      • San Diego, California, United States, 92103
        • University of California San Diego
      • San Francisco, California, United States, 94143
        • University of California San Francisco
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Denver
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University School of Medicine
    • Maryland
      • Baltimore, Maryland, United States, 21202
        • Mercy Medical Center
      • Bethesda, Maryland, United States, 20889
        • Walter Reed National Military Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
    • Missouri
      • Kansas City, Missouri, United States, 64131
        • Kansas City Research Institute
    • North Carolina
      • Durham, North Carolina, United States, 03125
        • Duke University Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Hospital of the University of Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15143
        • University of Pittsburg Medical Center
    • Texas
      • Arlington, Texas, United States, 76012
        • Texas Clinical Research Institute
      • Dallas, Texas, United States, 75203
        • Methodist Dallas Medical Center
      • Houston, Texas, United States, 77030
        • CHI St. Luke's Health Baylor College of Medicine
      • Houston, Texas, United States, 78234
        • Brooke Army Medical Center Ft. Sam
      • Live Oak, Texas, United States, 78233
        • Digestive Research Center
      • San Antonio, Texas, United States, 78215
        • American Research Corporation at Texas Liver Institute
    • Utah
      • Murray, Utah, United States, 84107
        • Intermountain Medical Center
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia
      • Falls Church, Virginia, United States, 22042
        • Inova Fairfax Hospital
      • Newport News, Virginia, United States, 23602
        • Mary Immaculate Hospital
      • Richmond, Virginia, United States, 23226
        • St. Mary's Hospital
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University Health System
    • Washington
      • Seattle, Washington, United States, 98104
        • Swedish Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Key Inclusion Criteria:

  • Males and non-pregnant, non-lactating females
  • Evidence of NASH with fibrosis on biopsy

Key Exclusion Criteria:

  • Cirrhosis of the liver (e.g. Brunt/Kleiner score of F4)
  • Other causes of liver disease including viral hepatitis and alcoholic liver disease
  • Any history of decompensated liver disease, including ascites, hepatic encephalopathy or variceal bleeding
  • History of liver transplantation
  • Alcohol consumption greater than 21 oz/week for males or 14 oz/week for females (1 oz/30 mL of alcohol is present in 1 12 oz/360 mL beer, 1 4 oz/120 mL glass of wine, and a 1 oz/30 mL measure of 40% proof alcohol)

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: SEL 6 mg
Selonsertib (SEL) 6 mg for 24 weeks.
Drug: SEL
SEL tablet administered orally once daily
Other Names:
  • GS-4997
Experimental: SEL 18 mg
SEL 18 mg for 24 weeks.
Drug: SEL
SEL tablet administered orally once daily
Other Names:
  • GS-4997
Experimental: SEL 6 mg+SIM 125 mg
SEL 6 mg plus SIM 125 mg for 24 weeks.
Drug: SEL
SEL tablet administered orally once daily
Other Names:
  • GS-4997
Biological: SIM
Simtuzumab (SIM) 125 mg/mL single-dose vials administered subcutaneously once weekly
Other Names:
  • GS-6624
Experimental: SEL 18 mg+SIM 125 mg
SEL 18 mg plus SIM 125 mg for 24 weeks.
Drug: SEL
SEL tablet administered orally once daily
Other Names:
  • GS-4997
Biological: SIM
Simtuzumab (SIM) 125 mg/mL single-dose vials administered subcutaneously once weekly
Other Names:
  • GS-6624
Experimental: SIM 125 mg
SIM 125 mg for 24 weeks.
Biological: SIM
Simtuzumab (SIM) 125 mg/mL single-dose vials administered subcutaneously once weekly
Other Names:
  • GS-6624

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs), and Any Grade ≥ 1 Laboratory Abnormality
Time Frame: Baseline up to last dose plus 30 days (up to Week 28)
Treatment-emergent events began on or after the first dosing date up to 30 days after the last dosing date or led to premature discontinuation of study drug. The severity of laboratory abnormalities was assessed as Grade 0, 1 (mild), 2 (moderate), 3 (severe), or 4 (potentially life threatening) using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03.
Baseline up to last dose plus 30 days (up to Week 28)
Number of Participants Who Prematurely Discontinued Study Drug or Study Due to Adverse Events
Time Frame: Baseline up to follow up visit (Week 28)
Baseline up to follow up visit (Week 28)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Gilead Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

  • Loomba R, Lawitz E, Mantry PS, Jayakumar S, Caldwell SH, Arnold H, et al. GS-4997, an inhibitor of apoptosis signal-regulating kinase (ASK1), alone or in combination with simtuzumab for the treatment of nonalcoholic steatohepatitis (NASH): a randomized, phase 2 trial. Hepatol 2016; 64 (6S): 1119A-1120A.
  • Diehl AM, French D, Xu R, et al. Treatment with selonsertib, an inhibitor of apoptosis signal-regulating kinase 1, hepatic phospho-p38 expression and markers of hepatocellular apoptosis and necrosis in patients with nonalcoholic steatohepatitis. J Hepatol 2017;66:S51. PS-090.
  • Middleton MS, Lawitz E, Jayakumar S, et al. Hepatic proton density fat fraction correlates with histologic measures of steatosis and is responsive to change in those measures in a multi-center nonalcoholic steatohepatitis clinical trial. J Hepatol 2017;66:S668. SAT-483.
  • Loomba R, Lawitz E, Ghalib R, et al. Longitudinal changes in liver stiffness by magnetic resonance elastography (MRE), liver fibrosis, and serum markers of fibrosis in a multi-center clinical trial in nonalcoholic steatohepatitis (NASH). J Hepatol 2017;66:S671. SAT-489.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 8, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 11, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 11, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 5, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 5, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 9, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 26, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 31, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GS-US-384-1497

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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