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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

Primary Purpose

Non-Alcoholic Steatohepatitis (NASH)

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
SEL
SIM
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Alcoholic Steatohepatitis (NASH) focused on measuring GS-4997, Non-alcoholic fatty liver disease (NAFLD), Fibrosis, Simtuzumab (SIM), Apoptosis signal-regulating kinase 1, ASK1 inhibitor

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Stanford University Medical Center
  • University of California San Diego
  • University of California San Francisco
  • University of Colorado Denver
  • Northwestern University
  • Indiana University School of Medicine
  • Mercy Medical Center
  • Walter Reed National Military Medical Center
  • Beth Israel Deaconess Medical Center
  • Kansas City Research Institute
  • Duke University Medical Center
  • Hospital of the University of Pennsylvania
  • University of Pittsburg Medical Center
  • Texas Clinical Research Institute
  • Methodist Dallas Medical Center
  • CHI St. Luke's Health Baylor College of Medicine
  • Brooke Army Medical Center Ft. Sam
  • Digestive Research Center
  • American Research Corporation at Texas Liver Institute
  • Intermountain Medical Center
  • University of Virginia
  • Inova Fairfax Hospital
  • Mary Immaculate Hospital
  • St. Mary's Hospital
  • Virginia Commonwealth University Health System
  • Swedish Medical Center
  • University of Calgary
  • Toronto Liver Centre

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

SEL 6 mg

SEL 18 mg

SEL 6 mg+SIM 125 mg

SEL 18 mg+SIM 125 mg

SIM 125 mg

Arm Description

Selonsertib (SEL) 6 mg for 24 weeks.

SEL 18 mg for 24 weeks.

SEL 6 mg plus SIM 125 mg for 24 weeks.

SEL 18 mg plus SIM 125 mg for 24 weeks.

SIM 125 mg for 24 weeks.

Outcomes

Primary Outcome Measures

Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs), and Any Grade ≥ 1 Laboratory Abnormality
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.
Number of Participants Who Prematurely Discontinued Study Drug or Study Due to Adverse Events

Secondary Outcome Measures

Full Information

First Posted
June 5, 2015
Last Updated
May 31, 2019
Sponsor
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT02466516
Brief Title
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
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
June 8, 2015 (Actual)
Primary Completion Date
October 11, 2016 (Actual)
Study Completion Date
October 11, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Alcoholic Steatohepatitis (NASH)
Keywords
GS-4997, Non-alcoholic fatty liver disease (NAFLD), Fibrosis, Simtuzumab (SIM), Apoptosis signal-regulating kinase 1, ASK1 inhibitor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
72 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SEL 6 mg
Arm Type
Experimental
Arm Description
Selonsertib (SEL) 6 mg for 24 weeks.
Arm Title
SEL 18 mg
Arm Type
Experimental
Arm Description
SEL 18 mg for 24 weeks.
Arm Title
SEL 6 mg+SIM 125 mg
Arm Type
Experimental
Arm Description
SEL 6 mg plus SIM 125 mg for 24 weeks.
Arm Title
SEL 18 mg+SIM 125 mg
Arm Type
Experimental
Arm Description
SEL 18 mg plus SIM 125 mg for 24 weeks.
Arm Title
SIM 125 mg
Arm Type
Experimental
Arm Description
SIM 125 mg for 24 weeks.
Intervention Type
Drug
Intervention Name(s)
SEL
Other Intervention Name(s)
GS-4997
Intervention Description
SEL tablet administered orally once daily
Intervention Type
Biological
Intervention Name(s)
SIM
Other Intervention Name(s)
GS-6624
Intervention Description
Simtuzumab (SIM) 125 mg/mL single-dose vials administered subcutaneously once weekly
Primary Outcome Measure Information:
Title
Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs), and Any Grade ≥ 1 Laboratory Abnormality
Description
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.
Time Frame
Baseline up to last dose plus 30 days (up to Week 28)
Title
Number of Participants Who Prematurely Discontinued Study Drug or Study Due to Adverse Events
Time Frame
Baseline up to follow up visit (Week 28)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
Stanford University Medical Center
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
University of California San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
University of Colorado Denver
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Indiana University School of Medicine
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Mercy Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21202
Country
United States
Facility Name
Walter Reed National Military Medical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20889
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Kansas City Research Institute
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64131
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
03125
Country
United States
Facility Name
Hospital of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Pittsburg Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15143
Country
United States
Facility Name
Texas Clinical Research Institute
City
Arlington
State/Province
Texas
ZIP/Postal Code
76012
Country
United States
Facility Name
Methodist Dallas Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75203
Country
United States
Facility Name
CHI St. Luke's Health Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Brooke Army Medical Center Ft. Sam
City
Houston
State/Province
Texas
ZIP/Postal Code
78234
Country
United States
Facility Name
Digestive Research Center
City
Live Oak
State/Province
Texas
ZIP/Postal Code
78233
Country
United States
Facility Name
American Research Corporation at Texas Liver Institute
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
Facility Name
Intermountain Medical Center
City
Murray
State/Province
Utah
ZIP/Postal Code
84107
Country
United States
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
Inova Fairfax Hospital
City
Falls Church
State/Province
Virginia
ZIP/Postal Code
22042
Country
United States
Facility Name
Mary Immaculate Hospital
City
Newport News
State/Province
Virginia
ZIP/Postal Code
23602
Country
United States
Facility Name
St. Mary's Hospital
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23226
Country
United States
Facility Name
Virginia Commonwealth University Health System
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
Swedish Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
University of Calgary
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N4Z6
Country
Canada
Facility Name
Toronto Liver Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M6H 3M1
Country
Canada

12. IPD Sharing Statement

Citations:
Citation
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.
Results Reference
result
Citation
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.
Results Reference
result
Citation
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.
Results Reference
result
Citation
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.
Results Reference
result

Learn more about this trial

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

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