Nonalcoholic Steatohepatitis (NASH)
Conditions
Keywords
Non-alcoholic fatty liver disease (NAFLD), Fibrosis, GS-9674
Brief summary
The primary objective of this study is to evaluate the safety and tolerability of GS-9674 in participants with nonalcoholic steatohepatitis (NASH).
Interventions
DRUGGS-9674
Tablet administered orally once daily
DRUGPlacebo to match GS-9674
Tablet(s) administered orally once daily
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Meets the following conditions: * A clinical diagnosis of nonalcoholic fatty liver disease (NAFLD) * Screening magnetic resonance imaging - proton density fat fraction (MRI-PDFF) with ≥ 8% steatosis * Screening magnetic resonance elastography (MRE) with liver stiffness ≥ 2.5 kilopascal (kPa) OR * A historical liver biopsy within 12 months of screening consistent with NASH with fibrosis, but not cirrhosis, and * No documented weight loss \> 5% between the date of the liver biopsy and screening. * Platelet count ≥ 150,000/mm\^3 * Albumin ≥ 3.3 g/dL * Serum creatinine ≤ upper limit of normal (ULN) Key
Exclusion criteria
* Pregnant or lactating females * Alanine aminotransferase (ALT) \> 5x upper limit of the normal range (ULN) * Other causes of liver disease including autoimmune, viral, and alcoholic liver disease * Cirrhosis of the liver * Prior history of decompensated liver disease, including ascites, hepatic encephalopathy, or variceal bleeding * Body mass index (BMI) \< 18 kg/m\^2 * Uncontrolled diabetes mellitus (hemoglobin A1c \> 9% at screening) * International normalized ratio (INR) \> 1.2 unless on anticoagulant therapy * Total bilirubin \> 1 x ULN, except with diagnosis of Gilbert's syndrome Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Safety of GS-9674 as Assessed By Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) | Up to 24 weeks plus 30 days | TEAEs were defined as 1 or both of the following: 1) Any adverse events (AE) with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug, 2) Any AEs leading to premature discontinuation of study drug. |
| Overall Safety of GS-9674 as Assessed By Percentage of Participants With Treatment-Emergent Laboratory Abnormalities | Up to 24 weeks plus 30 days | Treatment-emergent laboratory abnormalities are defined as values that increase at least 1 toxicity grade from baseline at any post-baseline time point, up to and including the date of last dose of study drug plus 30 days for participants who permanently discontinued study. |
Countries
Canada, Hong Kong, New Zealand, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in North America, Hong Kong, New Zealand, and Europe. The first participant was screened on 26 October 2016. The last study visit occurred on 09 January 2018.
Pre-assignment details
327 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| GS-9674 100 mg GS-9674 100 mg tablet once daily + PTM GS-9674 30 mg tablet once daily for 24 weeks. | 56 |
| GS-9674 30 mg GS-9674 30 mg tablet once daily + PTM GS-9674 100 mg tablet once daily for 24 weeks. | 56 |
| Placebo PTM GS-9674 30 mg tablet once daily + PTM GS-9674 100 mg tablet once daily for 24 weeks. | 28 |
| Total | 140 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 5 | 2 |
| Overall Study | Investigator's Discretion | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 2 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 1 |
| Overall Study | Withdrew Consent | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | GS-9674 100 mg | GS-9674 30 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 55 Years STANDARD_DEVIATION 10.5 | 51 Years STANDARD_DEVIATION 12.8 | 50 Years STANDARD_DEVIATION 9.9 | 53 Years STANDARD_DEVIATION 11.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 17 Participants | 19 Participants | 8 Participants | 44 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants | 37 Participants | 20 Participants | 96 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race, Customized American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Race, Customized Asian | 13 Participants | 5 Participants | 4 Participants | 22 Participants |
| Race/Ethnicity, Customized Race, Customized Black or African American | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Race, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race, Customized Other | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race, Customized White | 42 Participants | 47 Participants | 21 Participants | 110 Participants |
| Region of Enrollment Canada | 12 Participants | 7 Participants | 6 Participants | 25 Participants |
| Region of Enrollment Hong Kong | 5 Participants | 2 Participants | 3 Participants | 10 Participants |
| Region of Enrollment New Zealand | 1 Participants | 2 Participants | 1 Participants | 4 Participants |
| Region of Enrollment Switzerland | 0 Participants | 2 Participants | 2 Participants | 4 Participants |
| Region of Enrollment United Kingdom | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Region of Enrollment United States | 37 Participants | 43 Participants | 16 Participants | 96 Participants |
| Sex: Female, Male Female | 35 Participants | 37 Participants | 15 Participants | 87 Participants |
| Sex: Female, Male Male | 21 Participants | 19 Participants | 13 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 56 | 0 / 56 | 0 / 28 |
| other Total, other adverse events | 39 / 56 | 34 / 56 | 17 / 28 |
| serious Total, serious adverse events | 2 / 56 | 2 / 56 | 1 / 28 |
Outcome results
Primary
Overall Safety of GS-9674 as Assessed By Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
TEAEs were defined as 1 or both of the following: 1) Any adverse events (AE) with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug, 2) Any AEs leading to premature discontinuation of study drug.
Time frame: Up to 24 weeks plus 30 days
Population: Safety Analysis Set included all participants who took at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GS-9674 100 mg | Overall Safety of GS-9674 as Assessed By Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) | TEAEs | 89.3 Percentage of participants |
| GS-9674 100 mg | Overall Safety of GS-9674 as Assessed By Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to premature discontinuation of drug | 1.8 Percentage of participants |
| GS-9674 30 mg | Overall Safety of GS-9674 as Assessed By Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) | TEAEs | 76.8 Percentage of participants |
| GS-9674 30 mg | Overall Safety of GS-9674 as Assessed By Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to premature discontinuation of drug | 8.9 Percentage of participants |
| Placebo | Overall Safety of GS-9674 as Assessed By Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) | TEAEs | 67.9 Percentage of participants |
| Placebo | Overall Safety of GS-9674 as Assessed By Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to premature discontinuation of drug | 7.1 Percentage of participants |
Primary
Overall Safety of GS-9674 as Assessed By Percentage of Participants With Treatment-Emergent Laboratory Abnormalities
Treatment-emergent laboratory abnormalities are defined as values that increase at least 1 toxicity grade from baseline at any post-baseline time point, up to and including the date of last dose of study drug plus 30 days for participants who permanently discontinued study.
Time frame: Up to 24 weeks plus 30 days
Population: Safety Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GS-9674 100 mg | Overall Safety of GS-9674 as Assessed By Percentage of Participants With Treatment-Emergent Laboratory Abnormalities | Grade 3 | 7.1 Percentage of participants |
| GS-9674 100 mg | Overall Safety of GS-9674 as Assessed By Percentage of Participants With Treatment-Emergent Laboratory Abnormalities | Grade 2 | 37.5 Percentage of participants |
| GS-9674 100 mg | Overall Safety of GS-9674 as Assessed By Percentage of Participants With Treatment-Emergent Laboratory Abnormalities | Any Grade ≥ 1 | 89.3 Percentage of participants |
| GS-9674 100 mg | Overall Safety of GS-9674 as Assessed By Percentage of Participants With Treatment-Emergent Laboratory Abnormalities | Grade 1 | 35.7 Percentage of participants |
| GS-9674 100 mg | Overall Safety of GS-9674 as Assessed By Percentage of Participants With Treatment-Emergent Laboratory Abnormalities | Grade 4 | 8.9 Percentage of participants |
| GS-9674 30 mg | Overall Safety of GS-9674 as Assessed By Percentage of Participants With Treatment-Emergent Laboratory Abnormalities | Grade 2 | 37.5 Percentage of participants |
| GS-9674 30 mg | Overall Safety of GS-9674 as Assessed By Percentage of Participants With Treatment-Emergent Laboratory Abnormalities | Any Grade ≥ 1 | 92.9 Percentage of participants |
| GS-9674 30 mg | Overall Safety of GS-9674 as Assessed By Percentage of Participants With Treatment-Emergent Laboratory Abnormalities | Grade 1 | 42.9 Percentage of participants |
| GS-9674 30 mg | Overall Safety of GS-9674 as Assessed By Percentage of Participants With Treatment-Emergent Laboratory Abnormalities | Grade 3 | 10.7 Percentage of participants |
| GS-9674 30 mg | Overall Safety of GS-9674 as Assessed By Percentage of Participants With Treatment-Emergent Laboratory Abnormalities | Grade 4 | 1.8 Percentage of participants |
| Placebo | Overall Safety of GS-9674 as Assessed By Percentage of Participants With Treatment-Emergent Laboratory Abnormalities | Grade 4 | 3.6 Percentage of participants |
| Placebo | Overall Safety of GS-9674 as Assessed By Percentage of Participants With Treatment-Emergent Laboratory Abnormalities | Grade 3 | 14.3 Percentage of participants |
| Placebo | Overall Safety of GS-9674 as Assessed By Percentage of Participants With Treatment-Emergent Laboratory Abnormalities | Any Grade ≥ 1 | 92.9 Percentage of participants |
| Placebo | Overall Safety of GS-9674 as Assessed By Percentage of Participants With Treatment-Emergent Laboratory Abnormalities | Grade 2 | 25.0 Percentage of participants |
| Placebo | Overall Safety of GS-9674 as Assessed By Percentage of Participants With Treatment-Emergent Laboratory Abnormalities | Grade 1 | 50.0 Percentage of participants |