Compensated Cirrhosis, Primary Sclerosing Cholangitis
Conditions
Brief summary
The primary objective of this study is to assess the safety and tolerability of escalating doses of cilofexor (CILO) in participants with primary sclerosing cholangitis (PSC) and compensated cirrhosis.
Interventions
DRUGCilofexor
Tablets administered orally once daily
Sponsors
Gilead Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Diagnosis PSC based on cholangiogram (magnetic resonance cholangiopancreatography \[MRCP\], endoscopic retrograde cholangiopancreatography \[ERCP\], or percutaneous transhepatic cholangiogram \[PTC\]) or liver biopsy * Individuals have evidence of cirrhosis based on historical liver biopsy, abdominal imaging \[magnetic resonance imaging (MRI), computed tomography (CT), or Ultrasound\], or a screening FibroScan®, enhanced liver fibrosis (ELF)™, or FibroTest®. * Individual has the following laboratory parameters at the Screening visit, as determined by the central laboratory: * Estimated glomerular filtration rate (eGFR) \> 60 milliliter/minute (mL/min), as calculated by the Cockcroft-Gault equation * Alanine aminotransferase (ALT) ≤ 5 x upper limit of the normal (ULN) * Total 2 milligram/deciliter (mg/dL), unless the individual is known to have Gilbert's syndrome or hemolytic anemia * International normalized ratio (INR) ≤ 1.4, unless due to therapeutic anticoagulation * Platelet count ≥ 75,000/microliter (μL). Individuals with evidence of high-risk esophageal or gastric varices in the opinion of the investigator are excluded * Negative anti-mitochondrial antibody Key
Exclusion criteria
* Current or prior history of any of the following * Decompensated liver disease, including ascites, hepatic encephalopathy (HE), or variceal hemorrhage * Liver transplantation * Cholangiocarcinoma or hepatocellular carcinoma (HCC). * Model for End-stage Liver Disease (MELD) score \> 12 at Screening, unless due to an alternate etiology such as therapeutic anticoagulation * Child-Pugh (CP) score \> 6 at Screening, unless due to an alternative etiology such as Gilbert's syndrome or therapeutic anticoagulation * Current moderate to severely active inflammatory bowel disease (IBD) (including ulcerative colitis, Crohn's disease, and indeterminate colitis). * Note: Individuals with IBD who currently have an external ostomy bag and/or proctocolectomy are not subject to this exclusion criterion and need not undergo IBD Symptom Severity Assessment. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | First dose date up to 12 weeks plus 30 days | Treatment-emergent adverse events (TEAEs) were either defined any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug or any AEs leading to premature discontinuation of study drug. |
| Percentage of Participants Who Experienced Treatment Emergent Serious Adverse Events (SAEs) | First dose date up to 12 weeks plus 30 days | A treatment emergent SAE was defined as an event that, at any dose, resulted in the following: death ; life-threatening situation; in-patient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; a congenital anomaly/birth defect; a medically important event or reaction: such events may not be immediately life-threatening or result in death or hospitalization but may jeopardize the subject or may require intervention to prevent one of the other outcomes constituting SAEs. |
| Percentage of Participants Who Experienced Laboratory Abnormalities | First dose date up to 12 weeks plus 30 days | Treatment-emergent laboratory abnormalities are defined as values that increase at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last dose of study drug plus 30 days. Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at study sites in the United States.
Pre-assignment details
18 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Cilofexor Cilofexor 30 mg tablet orally once daily from Week 1 to Week 4, followed by cilofexor 60 mg (2 X 30 mg) tablets orally once daily from Week 5 to Week 8, followed by cilofexor 100 mg tablet orally once daily from Week 9 to Week 12. Participants received cilofexor for a total duration of 12 weeks. | 11 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrew consent | 1 |
Baseline characteristics
| Characteristic | Cilofexor |
|---|---|
| Age, Continuous | 49 years STANDARD_DEVIATION 14.1 |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 1 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 10 Participants |
| Race/Ethnicity, Customized Race Black or African American | 1 Participants |
| Race/Ethnicity, Customized Race White | 10 Participants |
| Region of Enrollment United States | 11 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 11 |
| other Total, other adverse events | 9 / 11 |
| serious Total, serious adverse events | 0 / 11 |
Outcome results
Primary
Percentage of Participants Who Experienced Laboratory Abnormalities
Treatment-emergent laboratory abnormalities are defined as values that increase at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last dose of study drug plus 30 days. Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening.
Time frame: First dose date up to 12 weeks plus 30 days
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cilofexor | Percentage of Participants Who Experienced Laboratory Abnormalities | Grade 1 | 54.5 percentage of participants |
| Cilofexor | Percentage of Participants Who Experienced Laboratory Abnormalities | Grade 2 | 36.4 percentage of participants |
| Cilofexor | Percentage of Participants Who Experienced Laboratory Abnormalities | Grade 3 | 9.1 percentage of participants |
| Cilofexor | Percentage of Participants Who Experienced Laboratory Abnormalities | Grade 4 | 0 percentage of participants |
Primary
Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
Treatment-emergent adverse events (TEAEs) were either defined any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug or any AEs leading to premature discontinuation of study drug.
Time frame: First dose date up to 12 weeks plus 30 days
Population: Safety Analysis Set included all participants who took at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cilofexor | Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | 81.8 percentage of participants |
Primary
Percentage of Participants Who Experienced Treatment Emergent Serious Adverse Events (SAEs)
A treatment emergent SAE was defined as an event that, at any dose, resulted in the following: death ; life-threatening situation; in-patient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; a congenital anomaly/birth defect; a medically important event or reaction: such events may not be immediately life-threatening or result in death or hospitalization but may jeopardize the subject or may require intervention to prevent one of the other outcomes constituting SAEs.
Time frame: First dose date up to 12 weeks plus 30 days
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cilofexor | Percentage of Participants Who Experienced Treatment Emergent Serious Adverse Events (SAEs) | 0 percentage of participants |