Non-Alcoholic Steatohepatitis (NASH)Phase 2NCT02466516
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
A Phase 2 study testing SEL and SIM in people with Non-Alcoholic Steatohepatitis (NASH), run by Gilead Sciences at 28 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Non-Alcoholic Steatohepatitis (NASH)
- What is being tested?
- SEL and SIM
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 28 sitesin 2 countries
- Study dates
- 8 Jun 2015to 11 Oct 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and non-pregnant, non-lactating females
- Evidence of NASH with fibrosis on biopsy
Who cannot join
- 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.
Trial locations and contacts
28 sites in 2 countries.
28 sites in 2 countries
United States26 sites
Texas Clinical Research Institute
Arlington, Texas, 76012
University of Colorado Denver
Aurora, Colorado, 80045
Mercy Medical Center
Baltimore, Maryland, 21202
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
University of Virginia
Charlottesville, Virginia, 22908
Northwestern University
Chicago, Illinois, 60611
Methodist Dallas Medical Center
Dallas, Texas, 75203
Duke University Medical Center
Durham, North Carolina, 03125
Inova Fairfax Hospital
Falls Church, Virginia, 22042
CHI St. Luke's Health Baylor College of Medicine
Houston, Texas, 77030
Brooke Army Medical Center Ft. Sam
Houston, Texas, 78234
Indiana University School of Medicine
Indianapolis, Indiana, 46202
Kansas City Research Institute
Kansas City, Missouri, 64131
Digestive Research Center
Live Oak, Texas, 78233
Intermountain Medical Center
Murray, Utah, 84107
Mary Immaculate Hospital
Newport News, Virginia, 23602
Stanford University Medical Center
Palo Alto, California, 94304
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
University of Pittsburg Medical Center
Pittsburgh, Pennsylvania, 15143
St. Mary's Hospital
Richmond, Virginia, 23226
Virginia Commonwealth University Health System
Richmond, Virginia, 23298
American Research Corporation at Texas Liver Institute
San Antonio, Texas, 78215
University of California San Diego
San Diego, California, 92103
University of California San Francisco
San Francisco, California, 94143
Swedish Medical Center
Seattle, Washington, 98104
Canada2 sites
University of Calgary
Calgary, Alberta, T2N4Z6
Toronto Liver Centre
Toronto, Ontario, M6H 3M1
About this study
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
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.
- Conditions
- Non-Alcoholic Steatohepatitis (NASH)
- Being tested
- SEL, SIM
- Keywords
- GS-4997, Non-alcoholic fatty liver disease (NAFLD), Fibrosis, Simtuzumab (SIM), Apoptosis signal-regulating kinase 1, ASK1 inhibitor
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SELDrug
Also called GS-4997
SEL tablet administered orally once daily
SIMBiological
Also called GS-6624
Simtuzumab (SIM) 125 mg/mL single-dose vials administered subcutaneously once weekly
| Study group | Role | What they receive |
|---|---|---|
| SEL 6 mg | Experimental | Selonsertib (SEL) 6 mg for 24 weeks. Receives: Drug: SEL |
| SEL 18 mg | Experimental | SEL 18 mg for 24 weeks. Receives: Drug: SEL |
| SEL 6 mg+SIM 125 mg | Experimental | SEL 6 mg plus SIM 125 mg for 24 weeks. Receives: Drug: SEL; Biological: SIM |
| SEL 18 mg+SIM 125 mg | Experimental | SEL 18 mg plus SIM 125 mg for 24 weeks. Receives: Drug: SEL; Biological: SIM |
| SIM 125 mg | Experimental | SIM 125 mg for 24 weeks. Receives: Biological: SIM |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: Baseline up to follow up visit (Week 28)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2015 (estimated)
- Study start8 Jun 2015
- Primary completion11 Oct 2016
- Study completion11 Oct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Non-Alcoholic Steatohepatitis (NASH)Studies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gilead Study Director, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02466516
- Sponsor's protocol ID
- GS-US-384-1497
- Status last verified
- May 2019
- First submitted
- 5 Jun 2015
- Last updated
- 26 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
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 at a glance
From the registry record, last updated by the sponsor on 26 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02466516
- Acronym / sponsor ID
- GS-US-384-1497
- Conditions
- Non-Alcoholic Steatohepatitis (NASH)
- Keywords
- GS-4997, Non-alcoholic fatty liver disease (NAFLD), Fibrosis, Simtuzumab (SIM), Apoptosis signal-regulating kinase 1, ASK1 inhibitor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- 8 Jun 2015 (actual)
- Primary completion
- 11 Oct 2016 (actual)
- Study completion
- 11 Oct 2016 (actual)
- First posted
- 9 Jun 2015 (estimated)
- Results
- Posted 26 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| SEL 6 mg | Experimental | Drug: SELSelonsertib (SEL) 6 mg for 24 weeks. |
| SEL 18 mg | Experimental | Drug: SELSEL 18 mg for 24 weeks. |
| SEL 6 mg+SIM 125 mg | Experimental | Drug: SEL, Biological: SIMSEL 6 mg plus SIM 125 mg for 24 weeks. |
| SEL 18 mg+SIM 125 mg | Experimental | Drug: SEL, Biological: SIMSEL 18 mg plus SIM 125 mg for 24 weeks. |
| SIM 125 mg | Experimental | Biological: SIMSIM 125 mg for 24 weeks. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Males and non-pregnant, non-lactating females
- Evidence of NASH with fibrosis on biopsy
Key exclusion criteria (6 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SELAlso: GS-4997SEL tablet administered orally once daily | Drug | SEL 18 mg, SEL 18 mg+SIM 125 mg, SEL 6 mg, SEL 6 mg+SIM 125 mg |
| SIMAlso: GS-6624Simtuzumab (SIM) 125 mg/mL single-dose vials administered subcutaneously once weekly | Biological | SEL 18 mg+SIM 125 mg, SEL 6 mg+SIM 125 mg, SIM 125 mg |
Primary outcome
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.
Number of Participants Who Prematurely Discontinued Study Drug or Study Due to Adverse Events
Time frame: Baseline up to follow up visit (Week 28)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publicationLoomba 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 publicationDiehl 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 publicationMiddleton 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 publicationLoomba 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gilead Study Director study director
Gilead Sciences
28 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SEL and SIM in people with Non-Alcoholic Steatohepatitis (NASH), run by Gilead Sciences at 28 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02466516, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2019.