Primary Sclerosing Cholangitis
Conditions
Brief summary
The primary objective of this study is to evaluate whether cilofexor reduces the risk of fibrosis progression among non-cirrhotic adults with primary sclerosing cholangitis (PSC).
Interventions
DRUGCilofexor
100 mg tablet administered orally once daily
DRUGPlacebo
Tablet 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: * Diagnosis of large duct PSC * Liver biopsy at screening that is deemed acceptable for interpretation and demonstrates stage F0 - F3 fibrosis in the opinion of the central reader * Individual has the following laboratory parameters at the screening visit, as determined by the central laboratory: * Platelet count ≥ 150,000/mm\^3 * Estimated glomerular filtration rate (eGFR) ≥ 30 milliliter/minute (mL/min), as calculated by the Cockcroft-Gault equation * Alanine transaminase (ALT) ≤ 8 x upper limit of the normal range (ULN) * Total bilirubin \< 2 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 * Negative anti-mitochondrial antibody Key
Exclusion criteria
* Current or prior history of any of the following: * Cirrhosis * Liver transplantation * Cholangiocarcinoma or hepatocellular carcinoma (HCC) * Ascending cholangitis within 30 days of screening * Presence of a percutaneous drain or biliary stent * Other causes of liver disease * Current or prior history of unstable cardiovascular disease * Current moderate to severe inflammatory bowel disease (IBD) (including ulcerative colitis, Crohn's disease, and indeterminate colitis) Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Progression of Liver Fibrosis at Blinded Phase Week 96 | Blinded Phase Week 96 | Progression of liver fibrosis was defined as having a ≥ 1-stage increase from baseline in fibrosis according to the Ludwig classification at Blinded Phase Week 96. The stages of fibrosis was assessed according to Ludwig classification. Ludwig classification fibrosis stages range from 0 to 4, with higher scores indicating greater fibrosis (0=no fibrosis, 4=cirrhosis). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experienced TEAEs in The OLE Phase | First dose date in the OLE Phase up to 45 weeks plus 30 days | An AE was any untoward medical occurrence in a clinical study participant administered a study drug that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a study drug, whether or not the AE is considered related to the study drug. For Blinded Study Phase and OLE Phase, TEAEs were defined as 1 or both of the following: 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 and/or any AEs leading to premature discontinuation of study drug. |
| Percentage of Participants Who Experienced Treatment-emergent Serious Adverse Events (SAEs) in the Blinded Phase | First dose date in the Blinded Phase up to 100.3 weeks plus 30 days | An SAE was defined as an event that, at any dose, results in the following: death, a life-threatening situation; in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect or a medically important event or reaction. |
| Percentage of Participants Who Experienced Treatment-emergent SAEs in the OLE Phase | First dose date in the OLE Phase up to 45 weeks plus 30 days | An SAE was defined as an event that, at any dose, results in the following: death, a life-threatening situation; in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect or a medically important event or reaction. |
| Change From Baseline in Serum Concentrations of Alkaline Phosphatase (ALP) at Blinded Phase Week 96 | Baseline, Blinded Phase Week 96 | — |
| Change From Baseline in Serum Concentrations of Alanine Aminotransferase (ALT) at Blinded Phase Week 96 | Baseline, Blinded Phase Week 96 | — |
| Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) in The Blinded Phase | First dose date in the Blinded Phase up to 100.3 weeks plus 30 days | An AE was any untoward medical occurrence in a clinical study participant administered a study drug that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a study drug, whether or not the AE is considered related to the study drug. For Blinded Study Phase and OLE Phase, TEAEs were defined as 1 or both of the following: 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 and/or any AEs leading to premature discontinuation of study drug. |
| Percentage of Participants With ≥ 25% Relative Reduction in Serum ALP Concentration From Baseline and No Worsening of Fibrosis According to the Ludwig Classification at Blinded Phase Week 96 | Baseline, Blinded Phase Week 96 | The stages of fibrosis was assessed according to Ludwig classification. Ludwig classification fibrosis stages range from 0 to 4, with higher scores indicating greater fibrosis (0=no fibrosis, 4=cirrhosis).The percentage of participants with ≥ 25% reduction in serum ALP Concentration from baseline and no increase in fibrosis according to the Ludwig Classification at Blinded Phase Week 96 was analyzed. |
| Percentage of Participants With Fibrosis Improvement According to the Ludwig Classification at Blinded Phase Week 96 | Blinded Phase Week 96 | Fibrosis improvement was defined as having ≥ 1-stage decrease from baseline in fibrosis according to the Ludwig classification score at Blinded Study Phase Week 96. The stages of fibrosis was assessed according to Ludwig classification. Ludwig classification fibrosis stages range from 0 to 4, with higher scores indicating greater fibrosis (0=no fibrosis, 4=cirrhosis). |
| Change From Baseline in Primary Sclerosing Cholangitis (PSC) Symptoms - Module 1 Based on Disease-specific Patient Reported Outcome (PSC-PRO) at Blinded Phase Week 96 | Baseline, Blinded Phase Week 96 | The PSC-PRO addressed the severity of common everyday symptoms of PSC (eg, pruritus, fatigue, and right upper quadrant abdominal discomfort); and their functional impact (eg, on physical function, activities of daily living, and work productivity, etc). PSC-PRO module 1 - PSC symptoms contains a total of 12 questions asking about the severity of specific PSC symptoms on a scale of 0 (no symptoms) to 10 (symptoms as bad as you could imagine) with a 24-hour recall period. The total score, which is computed as 12 times the average of nonmissing scores of the 12 questions, can potentially range between 0 and 120, with higher scores indicating more severe symptoms. A positive change from baseline indicates worsening of symptoms. |
| Change From Baseline in Enhanced Liver Fibrosis (ELF™ ) Test Score at Blinded Phase Week 96 | Baseline, Blinded Phase Week 96 | The Enhanced Liver Fibrosis (ELF™) test is a composite of three serum biomarkers of hepatobiliary fibrosis: hyaluronic acid, procollagen III amino-terminal peptide, and tissue inhibitor of metalloproteinase. A typical range for ELF™ test scores in PSC is between 6 and 14. Higher ELF™ test scores are associated with more severe liver disease. A positive change from baseline indicated worsening of fibrosis. |
| Change From Baseline in Liver Stiffness by FibroScan® at Blinded Phase Week 96 | Baseline, Blinded Phase Week 96 | Change in liver stiffness was measured by FibroScan® scores. FibroScan measures liver scarring by measuring the stiffness of the liver. It's normally between 2 and 6 kPa. Many people with liver disease(s) have a result that's higher than the normal range. Higher scores indicate increased scarring of the liver. A positive change from baseline indicates severe liver disease(s). |
| Change From Baseline in Serum Concentrations of Fasting Total Bile Acids at Blinded Phase Week 96 | Baseline, Blinded Phase Week 96 | — |
Countries
Australia, Austria, Belgium, Canada, Denmark, Finland, France, Germany, Israel, Italy, Japan, New Zealand, Spain, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in Europe, North America, Oceania, and Asia.
Pre-assignment details
587 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Cilofexor 100 mg (Blinded Phase) Participants received cilofexor 100 mg tablet, orally, once daily for up to 100.3 weeks. | 277 |
| Placebo (Blinded Phase) Participants received placebo to match cilofexor 100 mg tablet, orally, once daily for up to 98.1 weeks | 139 |
| Total | 416 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Blinded Treatment Phase (100.3 Weeks) | Adverse Event | 17 | 7 | 0 | 0 |
| Blinded Treatment Phase (100.3 Weeks) | Death | 1 | 0 | 0 | 0 |
| Blinded Treatment Phase (100.3 Weeks) | Investigator's discretion | 1 | 2 | 0 | 0 |
| Blinded Treatment Phase (100.3 Weeks) | Lost to Follow-up | 4 | 1 | 0 | 0 |
| Blinded Treatment Phase (100.3 Weeks) | Non-compliance with study drug | 0 | 1 | 0 | 0 |
| Blinded Treatment Phase (100.3 Weeks) | Pregnancy | 0 | 1 | 0 | 0 |
| Blinded Treatment Phase (100.3 Weeks) | Randomized but never treated | 1 | 2 | 0 | 0 |
| Blinded Treatment Phase (100.3 Weeks) | Study terminated by sponsor | 119 | 57 | 0 | 0 |
| Blinded Treatment Phase (100.3 Weeks) | Withdrew consent | 12 | 4 | 0 | 0 |
| Open-Label Extension Phase (45 Weeks) | Adverse Event | 0 | 0 | 3 | 1 |
| Open-Label Extension Phase (45 Weeks) | Lost to Follow-up | 0 | 0 | 0 | 2 |
| Open-Label Extension Phase (45 Weeks) | Study terminated by sponsor | 0 | 0 | 76 | 42 |
| Open-Label Extension Phase (45 Weeks) | Withdrew consent | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Cilofexor 100 mg (Blinded Phase) | Placebo (Blinded Phase) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical >=65 years | 18 Participants | 6 Participants | 24 Participants |
| Age, Categorical Between 18 and 65 years | 258 Participants | 133 Participants | 391 Participants |
| Age, Continuous | 43 years STANDARD_DEVIATION 13.1 | 44 years STANDARD_DEVIATION 12.8 | 44 years STANDARD_DEVIATION 13 |
| Alkaline Phosphatase (ALP) | 223 units per liter (U/L) STANDARD_DEVIATION 177.7 | 243 units per liter (U/L) STANDARD_DEVIATION 189.5 | 230 units per liter (U/L) STANDARD_DEVIATION 181.7 |
| Aspartate Aminotransferase (AST) | 49 U/L STANDARD_DEVIATION 34.1 | 51 U/L STANDARD_DEVIATION 34.6 | 50 U/L STANDARD_DEVIATION 34.2 |
| Enhanced Liver Fibrosis (ELF™) Test Score | 9.14 score on a scale STANDARD_DEVIATION 0.91 | 9.13 score on a scale STANDARD_DEVIATION 0.963 | 9.13 score on a scale STANDARD_DEVIATION 0.927 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 3 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 258 Participants | 130 Participants | 388 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 8 Participants | 6 Participants | 14 Participants |
| Fasting Total Bile Acids | 24.2 micromoles per liter (μmol/L) STANDARD_DEVIATION 37.57 | 18.6 micromoles per liter (μmol/L) STANDARD_DEVIATION 22.49 | 22.4 micromoles per liter (μmol/L) STANDARD_DEVIATION 33.36 |
| Fibroscan Score | 7.8 kilopascals (kPa) STANDARD_DEVIATION 4.91 | 8.0 kilopascals (kPa) STANDARD_DEVIATION 4.07 | 7.8 kilopascals (kPa) STANDARD_DEVIATION 4.64 |
| Race/Ethnicity, Customized Race Asian | 28 Participants | 10 Participants | 38 Participants |
| Race/Ethnicity, Customized Race Black or African American | 10 Participants | 7 Participants | 17 Participants |
| Race/Ethnicity, Customized Race Other or More Than One Race | 5 Participants | 0 Participants | 5 Participants |
| Race/Ethnicity, Customized Race Unknown or Not Reported | 6 Participants | 5 Participants | 11 Participants |
| Race/Ethnicity, Customized Race White | 228 Participants | 117 Participants | 345 Participants |
| Region of Enrollment Australia | 18 Participants | 13 Participants | 31 Participants |
| Region of Enrollment Austria | 3 Participants | 1 Participants | 4 Participants |
| Region of Enrollment Belgium | 4 Participants | 2 Participants | 6 Participants |
| Region of Enrollment Canada | 28 Participants | 10 Participants | 38 Participants |
| Region of Enrollment Denmark | 4 Participants | 3 Participants | 7 Participants |
| Region of Enrollment Finland | 11 Participants | 8 Participants | 19 Participants |
| Region of Enrollment France | 8 Participants | 6 Participants | 14 Participants |
| Region of Enrollment Germany | 13 Participants | 5 Participants | 18 Participants |
| Region of Enrollment Israel | 8 Participants | 3 Participants | 11 Participants |
| Region of Enrollment Italy | 17 Participants | 6 Participants | 23 Participants |
| Region of Enrollment Japan | 19 Participants | 8 Participants | 27 Participants |
| Region of Enrollment New Zealand | 4 Participants | 2 Participants | 6 Participants |
| Region of Enrollment Spain | 13 Participants | 3 Participants | 16 Participants |
| Region of Enrollment Switzerland | 2 Participants | 4 Participants | 6 Participants |
| Region of Enrollment United Kingdom | 11 Participants | 8 Participants | 19 Participants |
| Region of Enrollment United States | 114 Participants | 57 Participants | 171 Participants |
| Sex: Female, Male Female | 107 Participants | 52 Participants | 159 Participants |
| Sex: Female, Male Male | 170 Participants | 87 Participants | 257 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 278 | 0 / 141 | 0 / 80 | 0 / 45 |
| other Total, other adverse events | 232 / 277 | 109 / 139 | 34 / 80 | 24 / 45 |
| serious Total, serious adverse events | 53 / 277 | 26 / 139 | 9 / 80 | 1 / 45 |
Outcome results
Primary
Percentage of Participants With Progression of Liver Fibrosis at Blinded Phase Week 96
Progression of liver fibrosis was defined as having a ≥ 1-stage increase from baseline in fibrosis according to the Ludwig classification at Blinded Phase Week 96. The stages of fibrosis was assessed according to Ludwig classification. Ludwig classification fibrosis stages range from 0 to 4, with higher scores indicating greater fibrosis (0=no fibrosis, 4=cirrhosis).
Time frame: Blinded Phase Week 96
Population: Full Analysis Set included all randomized participants who took at least 1 dose of study drug. Participants in the Full Analysis Set who had nonmissing data at both baseline and Week 96 in the Blinded Study Phase were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cilofexor 100 mg (Blinded Phase) | Percentage of Participants With Progression of Liver Fibrosis at Blinded Phase Week 96 | 30.8 percentage of participants |
| Placebo (Blinded Phase) | Percentage of Participants With Progression of Liver Fibrosis at Blinded Phase Week 96 | 32.8 percentage of participants |
p-value: 0.418695% CI: [-15.2, 12.3]Mantel Haenszel
Secondary
Change From Baseline in Enhanced Liver Fibrosis (ELF™ ) Test Score at Blinded Phase Week 96
The Enhanced Liver Fibrosis (ELF™) test is a composite of three serum biomarkers of hepatobiliary fibrosis: hyaluronic acid, procollagen III amino-terminal peptide, and tissue inhibitor of metalloproteinase. A typical range for ELF™ test scores in PSC is between 6 and 14. Higher ELF™ test scores are associated with more severe liver disease. A positive change from baseline indicated worsening of fibrosis.
Time frame: Baseline, Blinded Phase Week 96
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Cilofexor 100 mg (Blinded Phase) | Change From Baseline in Enhanced Liver Fibrosis (ELF™ ) Test Score at Blinded Phase Week 96 | 0.27 score on a scale |
| Placebo (Blinded Phase) | Change From Baseline in Enhanced Liver Fibrosis (ELF™ ) Test Score at Blinded Phase Week 96 | 0.30 score on a scale |
p-value: 0.363695% CI: [-0.2, 0.14]ANCOVA
Secondary
Change From Baseline in Liver Stiffness by FibroScan® at Blinded Phase Week 96
Change in liver stiffness was measured by FibroScan® scores. FibroScan measures liver scarring by measuring the stiffness of the liver. It's normally between 2 and 6 kPa. Many people with liver disease(s) have a result that's higher than the normal range. Higher scores indicate increased scarring of the liver. A positive change from baseline indicates severe liver disease(s).
Time frame: Baseline, Blinded Phase Week 96
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Cilofexor 100 mg (Blinded Phase) | Change From Baseline in Liver Stiffness by FibroScan® at Blinded Phase Week 96 | 2.4 kilopascals (kPa) |
| Placebo (Blinded Phase) | Change From Baseline in Liver Stiffness by FibroScan® at Blinded Phase Week 96 | 2.8 kilopascals (kPa) |
p-value: 0.359595% CI: [-2.2, 1.5]ANCOVA
Secondary
Change From Baseline in Primary Sclerosing Cholangitis (PSC) Symptoms - Module 1 Based on Disease-specific Patient Reported Outcome (PSC-PRO) at Blinded Phase Week 96
The PSC-PRO addressed the severity of common everyday symptoms of PSC (eg, pruritus, fatigue, and right upper quadrant abdominal discomfort); and their functional impact (eg, on physical function, activities of daily living, and work productivity, etc). PSC-PRO module 1 - PSC symptoms contains a total of 12 questions asking about the severity of specific PSC symptoms on a scale of 0 (no symptoms) to 10 (symptoms as bad as you could imagine) with a 24-hour recall period. The total score, which is computed as 12 times the average of nonmissing scores of the 12 questions, can potentially range between 0 and 120, with higher scores indicating more severe symptoms. A positive change from baseline indicates worsening of symptoms.
Time frame: Baseline, Blinded Phase Week 96
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cilofexor 100 mg (Blinded Phase) | Change From Baseline in Primary Sclerosing Cholangitis (PSC) Symptoms - Module 1 Based on Disease-specific Patient Reported Outcome (PSC-PRO) at Blinded Phase Week 96 | Baseline | 11 score on a scale | Standard Deviation 11 |
| Cilofexor 100 mg (Blinded Phase) | Change From Baseline in Primary Sclerosing Cholangitis (PSC) Symptoms - Module 1 Based on Disease-specific Patient Reported Outcome (PSC-PRO) at Blinded Phase Week 96 | Change at Blinded Phase Week 96 | 1 score on a scale | Standard Deviation 9 |
| Placebo (Blinded Phase) | Change From Baseline in Primary Sclerosing Cholangitis (PSC) Symptoms - Module 1 Based on Disease-specific Patient Reported Outcome (PSC-PRO) at Blinded Phase Week 96 | Baseline | 11 score on a scale | Standard Deviation 11.8 |
| Placebo (Blinded Phase) | Change From Baseline in Primary Sclerosing Cholangitis (PSC) Symptoms - Module 1 Based on Disease-specific Patient Reported Outcome (PSC-PRO) at Blinded Phase Week 96 | Change at Blinded Phase Week 96 | 0 score on a scale | Standard Deviation 6.8 |
p-value: 0.727595% CI: [-1, 3]ANCOVA
Secondary
Change From Baseline in Serum Concentrations of Alanine Aminotransferase (ALT) at Blinded Phase Week 96
Time frame: Baseline, Blinded Phase Week 96
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Cilofexor 100 mg (Blinded Phase) | Change From Baseline in Serum Concentrations of Alanine Aminotransferase (ALT) at Blinded Phase Week 96 | -13 U/L |
| Placebo (Blinded Phase) | Change From Baseline in Serum Concentrations of Alanine Aminotransferase (ALT) at Blinded Phase Week 96 | -3 U/L |
p-value: 0.03995% CI: [-20, 1]ANCOVA
Secondary
Change From Baseline in Serum Concentrations of Alkaline Phosphatase (ALP) at Blinded Phase Week 96
Time frame: Baseline, Blinded Phase Week 96
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Cilofexor 100 mg (Blinded Phase) | Change From Baseline in Serum Concentrations of Alkaline Phosphatase (ALP) at Blinded Phase Week 96 | 0 units per liter (U/L) |
| Placebo (Blinded Phase) | Change From Baseline in Serum Concentrations of Alkaline Phosphatase (ALP) at Blinded Phase Week 96 | 3 units per liter (U/L) |
p-value: 0.388495% CI: [-28, 21]ANCOVA
Secondary
Change From Baseline in Serum Concentrations of Fasting Total Bile Acids at Blinded Phase Week 96
Time frame: Baseline, Blinded Phase Week 96
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Cilofexor 100 mg (Blinded Phase) | Change From Baseline in Serum Concentrations of Fasting Total Bile Acids at Blinded Phase Week 96 | 7.2 micromoles per liter (μmol/L) |
| Placebo (Blinded Phase) | Change From Baseline in Serum Concentrations of Fasting Total Bile Acids at Blinded Phase Week 96 | 9.8 micromoles per liter (μmol/L) |
p-value: 0.284595% CI: [-11.6, 6.4]ANCOVA
Secondary
Percentage of Participants Who Experienced TEAEs in The OLE Phase
An AE was any untoward medical occurrence in a clinical study participant administered a study drug that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a study drug, whether or not the AE is considered related to the study drug. For Blinded Study Phase and OLE Phase, TEAEs were defined as 1 or both of the following: 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 and/or any AEs leading to premature discontinuation of study drug.
Time frame: First dose date in the OLE Phase up to 45 weeks plus 30 days
Population: OLE Analysis Set included all participants who took at least 1 dose of study drug in the OLE Phase.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cilofexor 100 mg (Blinded Phase) | Percentage of Participants Who Experienced TEAEs in The OLE Phase | 66.3 percentage of participants |
| Placebo (Blinded Phase) | Percentage of Participants Who Experienced TEAEs in The OLE Phase | 73.3 percentage of participants |
Secondary
Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) in The Blinded Phase
An AE was any untoward medical occurrence in a clinical study participant administered a study drug that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a study drug, whether or not the AE is considered related to the study drug. For Blinded Study Phase and OLE Phase, TEAEs were defined as 1 or both of the following: 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 and/or any AEs leading to premature discontinuation of study drug.
Time frame: First dose date in the Blinded Phase up to 100.3 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 100 mg (Blinded Phase) | Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) in The Blinded Phase | 97.1 percentage of participants |
| Placebo (Blinded Phase) | Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) in The Blinded Phase | 95.0 percentage of participants |
Secondary
Percentage of Participants Who Experienced Treatment-emergent SAEs in the OLE Phase
An SAE was defined as an event that, at any dose, results in the following: death, a life-threatening situation; in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect or a medically important event or reaction.
Time frame: First dose date in the OLE Phase up to 45 weeks plus 30 days
Population: Participants in the OLE Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cilofexor 100 mg (Blinded Phase) | Percentage of Participants Who Experienced Treatment-emergent SAEs in the OLE Phase | 11.3 percentage of participants |
| Placebo (Blinded Phase) | Percentage of Participants Who Experienced Treatment-emergent SAEs in the OLE Phase | 2.2 percentage of participants |
Secondary
Percentage of Participants Who Experienced Treatment-emergent Serious Adverse Events (SAEs) in the Blinded Phase
An SAE was defined as an event that, at any dose, results in the following: death, a life-threatening situation; in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect or a medically important event or reaction.
Time frame: First dose date in the Blinded Phase up to 100.3 weeks plus 30 days
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cilofexor 100 mg (Blinded Phase) | Percentage of Participants Who Experienced Treatment-emergent Serious Adverse Events (SAEs) in the Blinded Phase | 19.1 percentage of participants |
| Placebo (Blinded Phase) | Percentage of Participants Who Experienced Treatment-emergent Serious Adverse Events (SAEs) in the Blinded Phase | 18.7 percentage of participants |
Secondary
Percentage of Participants With ≥ 25% Relative Reduction in Serum ALP Concentration From Baseline and No Worsening of Fibrosis According to the Ludwig Classification at Blinded Phase Week 96
The stages of fibrosis was assessed according to Ludwig classification. Ludwig classification fibrosis stages range from 0 to 4, with higher scores indicating greater fibrosis (0=no fibrosis, 4=cirrhosis).The percentage of participants with ≥ 25% reduction in serum ALP Concentration from baseline and no increase in fibrosis according to the Ludwig Classification at Blinded Phase Week 96 was analyzed.
Time frame: Baseline, Blinded Phase Week 96
Population: Participants in the Full Analysis Set with available data who had nonmissing data at both baseline and Week 96 in the blinded phase were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cilofexor 100 mg (Blinded Phase) | Percentage of Participants With ≥ 25% Relative Reduction in Serum ALP Concentration From Baseline and No Worsening of Fibrosis According to the Ludwig Classification at Blinded Phase Week 96 | 9.8 percentage of participants |
| Placebo (Blinded Phase) | Percentage of Participants With ≥ 25% Relative Reduction in Serum ALP Concentration From Baseline and No Worsening of Fibrosis According to the Ludwig Classification at Blinded Phase Week 96 | 6.6 percentage of participants |
p-value: 0.197895% CI: [-5.3, 13.5]Mantel Haenszel
Secondary
Percentage of Participants With Fibrosis Improvement According to the Ludwig Classification at Blinded Phase Week 96
Fibrosis improvement was defined as having ≥ 1-stage decrease from baseline in fibrosis according to the Ludwig classification score at Blinded Study Phase Week 96. The stages of fibrosis was assessed according to Ludwig classification. Ludwig classification fibrosis stages range from 0 to 4, with higher scores indicating greater fibrosis (0=no fibrosis, 4=cirrhosis).
Time frame: Blinded Phase Week 96
Population: Participants in the Full Analysis Set with available data who had nonmissing data at both baseline and Week 96 in the blinded phase were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cilofexor 100 mg (Blinded Phase) | Percentage of Participants With Fibrosis Improvement According to the Ludwig Classification at Blinded Phase Week 96 | 25.6 percentage of participants |
| Placebo (Blinded Phase) | Percentage of Participants With Fibrosis Improvement According to the Ludwig Classification at Blinded Phase Week 96 | 17.2 percentage of participants |
p-value: 0.079795% CI: [-3.5, 21.2]Mantel Haenszel