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).
Brief Title
Study of Cilofexor in Adults With Primary Sclerosing Cholangitis
Categories
Completion Date
Completion Date Type
Actual
Conditions
Primary Sclerosing Cholangitis
Eligibility 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/Exclusion criteria may apply
* 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/Exclusion criteria may apply
Inclusion Criteria
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
Inclusion/
* 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
Inclusion/
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
75 Years
Minimum Age
18 Years
NCT Id
NCT03890120
Org Class
Industry
Org Full Name
Gilead Sciences
Org Study Id
GS-US-428-4194
Overall Status
Terminated
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Efficacy of Cilofexor in Non-Cirrhotic Subjects With Primary Sclerosing Cholangitis
Primary Outcomes
Outcome Description
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).
Outcome Measure
Percentage of Participants With Progression of Liver Fibrosis at Blinded Phase Week 96
Outcome Time Frame
Blinded Phase Week 96
Secondary Ids
Secondary Id
2019-000204-14
Secondary Id
jRCT2080224728
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
First dose date in the Blinded Phase up to 100.3 weeks plus 30 days
Outcome Measure
Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) in The Blinded Phase
Outcome Description
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.
Outcome Time Frame
First dose date in the OLE Phase up to 45 weeks plus 30 days
Outcome Measure
Percentage of Participants Who Experienced TEAEs in The OLE Phase
Outcome Description
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.
Outcome Time Frame
First dose date in the Blinded Phase up to 100.3 weeks plus 30 days
Outcome Measure
Percentage of Participants Who Experienced Treatment-emergent Serious Adverse Events (SAEs) in the Blinded Phase
Outcome Description
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.
Outcome Time Frame
First dose date in the OLE Phase up to 45 weeks plus 30 days
Outcome Measure
Percentage of Participants Who Experienced Treatment-emergent SAEs in the OLE Phase
Outcome Time Frame
Baseline, Blinded Phase Week 96
Outcome Measure
Change From Baseline in Serum Concentrations of Alkaline Phosphatase (ALP) at Blinded Phase Week 96
Outcome Time Frame
Baseline, Blinded Phase Week 96
Outcome Measure
Change From Baseline in Serum Concentrations of Alanine Aminotransferase (ALT) at Blinded Phase Week 96
Outcome Time Frame
Baseline, Blinded Phase Week 96
Outcome Measure
Change From Baseline in Serum Concentrations of Fasting Total Bile Acids at Blinded Phase Week 96
Outcome Description
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.
Outcome Time Frame
Baseline, Blinded Phase Week 96
Outcome Measure
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
Outcome Description
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).
Outcome Time Frame
Blinded Phase Week 96
Outcome Measure
Percentage of Participants With Fibrosis Improvement According to the Ludwig Classification at Blinded Phase Week 96
Outcome Description
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.
Outcome Time Frame
Baseline, Blinded Phase Week 96
Outcome Measure
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
Outcome Description
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.
Outcome Time Frame
Baseline, Blinded Phase Week 96
Outcome Measure
Change From Baseline in Enhanced Liver Fibrosis (ELF™ ) Test Score at Blinded Phase Week 96
Outcome Description
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).
Outcome Time Frame
Baseline, Blinded Phase Week 96
Outcome Measure
Change From Baseline in Liver Stiffness by FibroScan® at Blinded Phase Week 96
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
75
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Samuel Sigal
Investigator Email
ssigal@montefiore.org
Investigator Phone
718-920-6240