Nonalcoholic Steatohepatitis (NASH)
Conditions
Brief summary
The primary objective of this study is to evaluate the safety and tolerability of firsocostat in adults with nonalcoholic steatohepatitis (NASH).
Interventions
DRUGFirsocostat
Capsules orally once daily.
DRUGPlacebo
Placebo matched to firsocostat orally once daily.
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
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 all of 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 kPa * OR * A historical liver biopsy consistent with NASH and non-cirrhotic fibrosis * Platelet count ≥ 100,000/mm\^3 * Creatinine Clearance (CLcr ) as calculated by the Cockcroft-Gault equation ≥ 60 ml/min Key
Exclusion criteria
* Pregnant or lactating females * Alanine aminotransferase (ALT) \> 5 x 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 * 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 |
|---|---|
| Percentage of Participants Experiencing Treatment-Emergent Adverse Events | First Dose date up to last dose (Week 12) plus 30 days |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at study sites in United States. The first participant was screened on 08 August 2016. The last study visit occurred on 18 July 2017.
Pre-assignment details
433 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Firsocostat 5 mg Participants received firsocostat 1 x 5 mg + 1 x placebo matched to firsocostat 5 mg + 2 x placebo matched to firsocostat 10 mg capsules orally once daily for 12 weeks. | 51 |
| Firsocostat 20 mg Participants received firsocostat 2 x 10 mg + 2 x placebo matched to firsocostat 5 mg capsules orally once daily for 12 weeks. | 49 |
| Placebo Participants received 2 x placebo matched to firsocostat 5 mg + 2 x placebo matched to firsocostat 10 mg capsules orally once daily for 12 weeks. | 26 |
| Total | 126 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 3 | 0 |
| Overall Study | Randomized but Never Treated | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 0 | 0 |
Baseline characteristics
| Characteristic | Firsocostat 20 mg | Placebo | Total | Firsocostat 5 mg |
|---|---|---|---|---|
| Age, Continuous | 54 years STANDARD_DEVIATION 12.2 | 56 years STANDARD_DEVIATION 9.6 | 54 years STANDARD_DEVIATION 11.5 | 53 years STANDARD_DEVIATION 11.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 23 Participants | 8 Participants | 47 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants | 18 Participants | 79 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 0 Participants | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Asian | 1 Participants | 1 Participants | 7 Participants | 5 Participants |
| Race/Ethnicity, Customized Race Black or African American | 2 Participants | 1 Participants | 6 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Others | 2 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Race White | 44 Participants | 23 Participants | 109 Participants | 42 Participants |
| Sex: Female, Male Female | 33 Participants | 19 Participants | 82 Participants | 30 Participants |
| Sex: Female, Male Male | 16 Participants | 7 Participants | 44 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 0 / 49 | 0 / 26 |
| other Total, other adverse events | 26 / 51 | 29 / 49 | 11 / 26 |
| serious Total, serious adverse events | 2 / 51 | 2 / 49 | 0 / 26 |
Outcome results
Primary
Percentage of Participants Experiencing Treatment-Emergent Adverse Events
Time frame: First Dose date up to last dose (Week 12) plus 30 days
Population: The Safety Analysis Set included participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Firsocostat 5 mg | Percentage of Participants Experiencing Treatment-Emergent Adverse Events | 70.6 percentage of participants |
| Firsocostat 20 mg | Percentage of Participants Experiencing Treatment-Emergent Adverse Events | 71.4 percentage of participants |
| Placebo | Percentage of Participants Experiencing Treatment-Emergent Adverse Events | 61.5 percentage of participants |