A Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of EDP-305 in Subjects With Primary Biliary Cholangitis
Primary Purpose
Primary Biliary Cholangitis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
EDP-305 1 mg
EDP-305 2.5 mg
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Primary Biliary Cholangitis focused on measuring PBC, Primary Biliary Cholangitis (PBC)
Eligibility Criteria
Inclusion Criteria:
- An informed consent document signed and dated by the subject.
- Male and female subjects of any ethnic origin between the ages of 18 and 75 years, inclusive
Male or female with a diagnosis of PBC by at least two of the following criteria:
- History of ALP above ULN for at least six months
- Positive Anti-Mitochondrial Antibodies (AMA) titers (>1/40 on immunofluorescence or M2 positive by enzyme linked immunosorbent assay (ELISA) or positive PBC-specific antinuclear antibodies)
- For subjects with no documented liver biopsy performed within 2 years, subjects must undergo a transient elastography (Fibroscan) showing liver stiffness < 14.0 kPA
- Must be on a stable dose of UDCA12-20 mg/kg/day for at least 6 months prior to Screening or intolerant of UDCA in the opinion of the Investigator (no UDCA for at least 12 weeks prior to Screening)
- Alkaline Phosphatase (ALP) ≥ 1.67 × ULN and/or total bilirubin >ULN but < 2×ULN (<2.4 mg/dL)
- Subjects must have Screening laboratory values for Hepatitis B surface antigen (HBsAg), anti-HCV antibodies and HCV RNA negative and Human Immunodeficiency Virus (HIV) 1 and 2 antibodies (Ab) as seronegative. Note: subjects previously infected by chronic hepatitis C and treated with direct acting antivirals (DAAs) with sustained virologic response (SVR) for at least 3 years will be allowed.
- Female subjects of childbearing potential must agree to use two effective methods of contraception from the date of Screening until 90 days after the last dose of EDP-305.
- All male participants who have not had a vasectomy must use effective contraception from Day -1 to 90 days after their last dose of study drug.
- Male subjects must agree to refrain from sperm donation from the date of Screening until 90 days after their last dose of study drug
- Screening body mass index (BMI) of ≥18 kg/m2
- Subject must be willing and able to adhere to the assessments, visit schedule, prohibitions and restrictions, as described in this protocol
Exclusion Criteria:
Laboratory Screening Results:
- AST >5 x ULN
- ALT >5 x ULN
- Patients with Gilbert's syndrome will not be allowed due to interpretability of bilirubin levels
- Total white blood cells (WBC) <3000 cells/mm3
- Absolute neutrophil count (ANC) <1500 cells/mm3
- Platelet count <140,000/mm3
- Prothrombin time (international normalized ratio, INR) >1.2
- Serum creatinine >2 mg/dL or creatinine clearance <60 mL/min (based on Cockroft-Gault Method)
- Suspected to have relevant nonalcoholic fatty liver disease (NAFLD) as based on the judgment of the Investigator at Screening
- Use of immunosuppressants known to have an effect on the liver of patients with PBC (eg, colchicine, methotrexate, azathioprine, or systemic steroids) in the three months preceding screening
- Current use of fibrates, including fenofibrates. Note: Subjects who discontinued fibrates for at least 3 months before Screening can participate
- Use of an experimental treatment for PBC within the past 6 months
- Co-existing liver or biliary diseases, such as primary sclerosing cholangitis, choledocholithiasis, acute or chronic hepatitis, autoimmune hepatitis, alcoholic liver disease, nonalcoholic steatohepatitis (NASH), acute infection of bile duct system or gall bladder, history of gastrointestinal bleeding (secondary to portal hypertension), cirrhosis, cholangiocarcinoma diagnosed or suspected liver cancers
- Cirrhosis with or without complications, including history or presence of: spontaneous bacterial peritonitis, hepatocellular carcinoma
- Hepatorenal syndrome (type I or II) or Screening serum creatinine > 2 mg/dL (178 μmol/L)
- Prior variceal hemorrhage, uncontrolled encephalopathy, Child-Pugh Class A, B and C, esophageal varices, or refractory ascites within the previous 6 months of Screening (defined as date informed consent signed)
- Medical conditions that may cause nonhepatic increases in ALP (e.g., Paget's disease)
- Use of a new statin regimen from Screening and throughout study duration. NOTE: Subjects on a stable dose of statins for at least 3 months prior to Screening are allowed. No dose modification during the study will be allowed.
- Use of immunosuppressants (eg, systemic corticosteroids) for more than 2 consecutive weeks in duration within 1 year prior to Screening.
Sites / Locations
- Digestive Health Specialists of the Southeast
- Arkansas Diagnostic Center
- Texas Clinical Research Institute
- Southern California Research Center
- Cedars-Sinai Medical Center
- California Liver Research Institue
- Pasadena Liver Center
- Inland Empire Liver Foundation
- California Pacific Medical Center
- South Denver Gastroenterology - Swedish Medical Center Office
- Yale School of Medicine
- Gastroenterology Consultants of Clearwater
- Nature Coast Clinical Research
- University of Miami Leonard M. Miller School of Medicine
- Consultative Gastroenterology
- Northwestern University
- University of Iowa Hospitals and Clinics
- Louisiana Research Center
- Mercy Medical Center-McAuley Plaza
- Johns Hopkins University
- Digestive Disease Associates
- Massachusetts General Hospital
- Beth Israel Deaconess Medical Center
- Henry Ford Hospital
- CHI Health
- Dartmouth-Hitchcock Medical Center
- Montefiore Medical Center - Bronx
- Northwell Health
- Concorde Medical Group
- Mount Sinai Beth Isreal
- Weill Cornell Medical College
- Icahn School of Medicine at Mount Sinai
- University of Pittsburgh Medical Center - Center for Liver Disease
- The Liver Institute at Methodist Dallas Medical Center
- Liver Consultants of Texas
- Baylor Saint Luke's Medical Center
- American Research Corporation at the Texas Liver Institute
- Liver Institute of Virginia-Bremo
- Swedish First Hill Campus
- University of Washington
- Nepean Hospital
- Monash Medical Centre
- Linear Clinical Research
- Klinikum Klagenfurt Am Wörthersee
- Medizinische Universität Innsbruck
- Klinikum Wels-Grieskirchen
- CHU de Liège, Cardiology Dept.
- Ziekenhuis Oost-Limburg
- Universitair Ziekenhuis Gent
- London Health Sciences Centre University Hospital
- Toronto General Hospital
- Toronto Liver Center
- Nouvel Hôpital Civil
- Hôpital Haut-Lévêque
- Hôpital Saint-Antoine
- Hôpital Paul Brousse
- Hôpital Saint-Eloi
- Centre Hospitalier Régional Universitaire de Lille
- Centre Hospitalier Universitaire Amines-Picardie Hôpital Sud
- Hôpital de la Croix Rousse
- Universitätsklinikum Würzburg
- Universitätsklinikum Frankfurt
- Universitätsklinikum Bonn
- Universitaetsklinikum Essen
- Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
- Universitätsklinikum Leipzig
- Charité Universitätsmedizin Berlin
- Vrije Universiteit Medisch Centrum
- Leiden Universitair Medisch Centrum
- Universitair Medisch Centrum Utrecht
- Hospital Universitario Donostia
- Hospital Universitario Virgen de la Arrixaca
- Hospital Universitari Vall d'Hebrón
- Hospital Universitario Ramón Y Cajal
- Hospital Universitario Marqués de Valdecilla
- Hospital Universitario Virgen del Rocio
- Hospital Universitari i Politecnic La Fe de Valencia
- Universidad de Valladolid - Hospital Universitario Rio Hortega
- University Hospitals Birmingham NHS Foundation Trust
- Cambridge University Hospitals NHS Foundation Trust
- The Leeds Teaching Hospitals NHS Trust
- King's College Hospital NHS Foundation Trust
- Norfolk and Norwich University Hospitals NHS Foundation Trust
- Queen's Medical Centre - Nottingham
- Portsmouth Hospitals NHS Trust
- NHS Lothian
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
EDP-305 1 mg
EDP-305 2.5 mg
Placebo
Arm Description
Subjects will take 2 tablets once a day orally for 12 weeks
Subjects will take 2 tablets once a day orally for 12 weeks
Subjects will take two tablets once a day orally for 12 weeks
Outcomes
Primary Outcome Measures
Percentage of Participants With At Least a 20% Reduction in Alkaline Phosphatase (ALP) or Normalization of ALP at Week 12 Compared to Baseline
Percent change was calculated as [(ALP at Week 12 - ALP at Baseline)/ALP at Baseline] *100. The participant was considered to have successfully achieved a 20% reduction in ALP if the result was ≤-20. The participant was considered to have successfully achieved ALP normalization if ALP was abnormal at Baseline and normal at Week 12.
Secondary Outcome Measures
Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE) During On-Treatment Period
An adverse event (AE) was defined as any event, side effect, or untoward medical occurrence in a subject enrolled in a clinical trial whether or not it is considered to have a causal relationship to the study drug. A TEAE was an AE that first occurred or began previous to and worsened on or after the first dose date and before the last dose date +7 days.
Percentage of Participants With a Treatment-Emergent Serious Adverse Event (SAE) During On-Treatment Period
A SAE is any untoward medical occurrence at any dose that results in death, is a life-threatening event, requires inpatient hospitalization or prolonged hospitalization of an existing hospitalization, results in permanent or prolonged disability or incapacity, is a congenital anomaly or birth defect in the offspring of a study subjects, or is a medically important event.
Percentage of Participants Who Stopped Study Treatment Due to a Treatment-Emergent Adverse Event (TEAE) During On-Treatment Period
An adverse event (AE) was defined as any event, side effect, or untoward medical occurrence in a subject enrolled in a clinical trial whether or not it is considered to have a causal relationship to the study drug. A TEAE was an AE that first occurred or began previous to and worsened on or after the first dose date and before the last dose date +7 days.
Change From Baseline to Week 12 in Total, Conjugated and Unconjugated Bilirubin
The data presented below was measured using least square mean change from baseline.
Change From Baseline to Week 12 in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT)
Change From Baseline to Week 12 in Noninvasive Liver Fibrosis Markers: Enhanced Liver Fibrosis (ELF) Panel and N-terminal Type III Collagen Propeptide (PRO C3)
The ELF panel included hyaluronic acid (HA), procollagen III amino terminal peptide (PIIINP), and tissue inhibitor of metalloproteinase 1 (TIMP 1). This endpoint also presents PRO C3 results.
Change From Baseline to Week 12 in Noninvasive Liver Fibrosis Markers: AST to Platelet Ratio Index (APRI) Score
APRI was calculated as ([AST level/AST upper limit of normal]/[Platelet count 1^09/L])×100. AST is aspartate aminotransferase. The aspartate transaminase to platelet ratio index (APRI) is used to assess liver fibrosis in participants with chronic liver disease. Scores range from 0 to ≥ 2.0, with scores < 0.5 predictive of no liver fibrosis; scores >1.5 significant fibrosis; and scores > 2.0 indicative of cirrhosis. A negative change from baseline indicates a decrease in fibrosis.
Change From Baseline to Week 12 in Noninvasive Liver Fibrosis Markers: Fibrosis-4 (FIB-4) Score
Fibrosis-4 is the ratio of age in years and aminotransferase to platelet count. It is a non-invasive hepatic fibrosis index score that is calculated using formula: FIB-4 = (Age [years] x AST [U/L]) / (platelets [10^9/L] x (square root of ALT [U/L])). A FIB-4 index of < 1.45 indicates no or moderate fibrosis and an index of > 3.25 indicates extensive fibrosis/cirrhosis. A positive change from Baseline indicates increased fibrosis.
Change From Baseline to Week 12 in Fibrinogen and C Reactive Protein (CRP) Levels
Change From Baseline to Week 12 in Interleukin (IL) and Tumor Necrosis Factor (TNF) Levels
For IL, both IL6 and IL1β variants were analysed. For TNF, both TNF α and TNF β (also known as lymphotoxin alpha) variants were analyzed.
Change From Baseline to Week 12 in Haptoglobin and Alpha2 Macroglobulin Levels
Change From Baseline to Week 12 in Triglycerides (TG), Total Cholesterol (TC), High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C)
Change From Baseline to Week 12 in Domain and Total Scores on the 5D-Itch Scale
The 5D-Itch scale is a multidimensional questionnaire completed by participants to quantify the magnitude of pruritus, assessed considering the past 2 weeks. Scale range is 1 to 5 covering five dimensions: duration (1=Less than 6 hrs/day to 5=All day), degree (1=Not present to 5=Unbearable), direction (1=Completely resolved to 5=Getting worse), disability (for Sleep rated as 1=Never affects sleep to 5=Delays falling asleep and frequently wakes me up at night; for Leisure/Social, Housework/Errands and Work/School rated as 1=Never affects activity to 5=Always affects activity), and distribution (assess if itching is present in 16 body locations, scored as 1=present at 0-2 locations to 5=present at 14-16 locations). Total scores (including highest disability score obtained from any of the daily activities) ranged between 5 and 25 where higher scores indicated more severe itching. Negative change scores indicate improvement from the baseline score.
Change From Baseline to Week 12 in Visual Analog Score (VAS) for Itching
An itch VAS (0-100mm) was used to record the intensity of the event. Participants drew a line on a scale corresponding to the maximum intensity of itch. Lines drawn towards the right of the line indicated greater itching and higher scores indicated more severe itching. Negative change from baseline indicates decrease in itching.
Change From Baseline to Week 12 in Domain Scores on the Primary Biliary Cholangitis-40 (PBC-40) Quality of Life (QoL) Assessment
The PBC-40 is a survey measuring health related quality of life in participants with PBC. The 40 questions from the PBC-40 questionnaire are scored from 1-5, with 5 representing the highest impact and 1 the lowest impact of PBC on the quality of life. Six domains were computed from the 40 questions: symptoms (score range 7-35), itch (0-15), fatigue (11-55), cognition (6-30), social (8-50) and emotional (1-15). Higher scores indicate worse quality of life and negative change scores indicate improvement from the baseline score.
Maximum Plasma Concentration (Cmax) of EDP-305 and Its Metabolites
Metabolites of EDP-305 are EP-022571, EP-022572, and EP-022679.
Time to Maximum Plasma Concentration (Tmax) of EDP-305 and Its Metabolites
Metabolites of EDP-305 are EP-022571, EP-022572, and EP-022679.
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of EDP-305 and Its Metabolites
Metabolites of EDP-305 are EP-022571, EP-022572, and EP-022679.
Percentage Change From Baseline to Week 12 in Fibroblast Growth Factor 19 (FGF19), 7α-OH-4-cholesten-3-one (C4) and Bile Acid (BA) Concentrations
FGF19 was measured in plasma. BA was measured in serum. C4 was measured in serum.
Percentage Change From Baseline to Week 12 in AUC0-8 and AUC2-8 of Fibroblast Growth Factor 19 (FGF19), 7α-OH-4-cholesten-3-one (C4) and Bile Acid (BA)
AUC0-8 is area under the biomarker concentration-time curve from time zero to 8 hours. AUC2-8 is area under the biomarker concentration-time curve from 2 hours to 8 hours. FGF19 was measured in plasma. BA was measured in serum. C4 was measured in serum.
Full Information
NCT ID
NCT03394924
First Posted
December 23, 2017
Last Updated
April 27, 2021
Sponsor
Enanta Pharmaceuticals, Inc
Collaborators
Pharmaceutical Research Associates, Triangle Biostatistics
1. Study Identification
Unique Protocol Identification Number
NCT03394924
Brief Title
A Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of EDP-305 in Subjects With Primary Biliary Cholangitis
Official Title
A Phase 2 Dose Ranging, Randomized, Double Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of EDP-305 in Subjects With Primary Biliary Cholangitis (PBC) With or Without an Inadequate Response to Ursodeoxycholic Acid (UDCA)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2020
Overall Recruitment Status
Completed
Study Start Date
December 27, 2017 (Actual)
Primary Completion Date
December 19, 2019 (Actual)
Study Completion Date
January 16, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Enanta Pharmaceuticals, Inc
Collaborators
Pharmaceutical Research Associates, Triangle Biostatistics
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
A randomized, double-blind study to assess the safety, tolerability, PK and efficacy of EDP-305 in subjects with primary biliary cholangitis
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Biliary Cholangitis
Keywords
PBC, Primary Biliary Cholangitis (PBC)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
68 (Actual)
8. Arms, Groups, and Interventions
Arm Title
EDP-305 1 mg
Arm Type
Experimental
Arm Description
Subjects will take 2 tablets once a day orally for 12 weeks
Arm Title
EDP-305 2.5 mg
Arm Type
Experimental
Arm Description
Subjects will take 2 tablets once a day orally for 12 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects will take two tablets once a day orally for 12 weeks
Intervention Type
Drug
Intervention Name(s)
EDP-305 1 mg
Intervention Description
Two tablets daily for 12 weeks
Intervention Type
Drug
Intervention Name(s)
EDP-305 2.5 mg
Intervention Description
Two tablets daily for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Two tablets daily for 12 weeks
Primary Outcome Measure Information:
Title
Percentage of Participants With At Least a 20% Reduction in Alkaline Phosphatase (ALP) or Normalization of ALP at Week 12 Compared to Baseline
Description
Percent change was calculated as [(ALP at Week 12 - ALP at Baseline)/ALP at Baseline] *100. The participant was considered to have successfully achieved a 20% reduction in ALP if the result was ≤-20. The participant was considered to have successfully achieved ALP normalization if ALP was abnormal at Baseline and normal at Week 12.
Time Frame
Baseline and Week 12
Secondary Outcome Measure Information:
Title
Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE) During On-Treatment Period
Description
An adverse event (AE) was defined as any event, side effect, or untoward medical occurrence in a subject enrolled in a clinical trial whether or not it is considered to have a causal relationship to the study drug. A TEAE was an AE that first occurred or began previous to and worsened on or after the first dose date and before the last dose date +7 days.
Time Frame
Up to approximately Week 12
Title
Percentage of Participants With a Treatment-Emergent Serious Adverse Event (SAE) During On-Treatment Period
Description
A SAE is any untoward medical occurrence at any dose that results in death, is a life-threatening event, requires inpatient hospitalization or prolonged hospitalization of an existing hospitalization, results in permanent or prolonged disability or incapacity, is a congenital anomaly or birth defect in the offspring of a study subjects, or is a medically important event.
Time Frame
Up to approximately Week 12
Title
Percentage of Participants Who Stopped Study Treatment Due to a Treatment-Emergent Adverse Event (TEAE) During On-Treatment Period
Description
An adverse event (AE) was defined as any event, side effect, or untoward medical occurrence in a subject enrolled in a clinical trial whether or not it is considered to have a causal relationship to the study drug. A TEAE was an AE that first occurred or began previous to and worsened on or after the first dose date and before the last dose date +7 days.
Time Frame
Up to approximately Week 12
Title
Change From Baseline to Week 12 in Total, Conjugated and Unconjugated Bilirubin
Description
The data presented below was measured using least square mean change from baseline.
Time Frame
Baseline and Week 12
Title
Change From Baseline to Week 12 in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT)
Time Frame
Baseline and Week 12
Title
Change From Baseline to Week 12 in Noninvasive Liver Fibrosis Markers: Enhanced Liver Fibrosis (ELF) Panel and N-terminal Type III Collagen Propeptide (PRO C3)
Description
The ELF panel included hyaluronic acid (HA), procollagen III amino terminal peptide (PIIINP), and tissue inhibitor of metalloproteinase 1 (TIMP 1). This endpoint also presents PRO C3 results.
Time Frame
Baseline and Week 12
Title
Change From Baseline to Week 12 in Noninvasive Liver Fibrosis Markers: AST to Platelet Ratio Index (APRI) Score
Description
APRI was calculated as ([AST level/AST upper limit of normal]/[Platelet count 1^09/L])×100. AST is aspartate aminotransferase. The aspartate transaminase to platelet ratio index (APRI) is used to assess liver fibrosis in participants with chronic liver disease. Scores range from 0 to ≥ 2.0, with scores < 0.5 predictive of no liver fibrosis; scores >1.5 significant fibrosis; and scores > 2.0 indicative of cirrhosis. A negative change from baseline indicates a decrease in fibrosis.
Time Frame
Baseline and Week 12
Title
Change From Baseline to Week 12 in Noninvasive Liver Fibrosis Markers: Fibrosis-4 (FIB-4) Score
Description
Fibrosis-4 is the ratio of age in years and aminotransferase to platelet count. It is a non-invasive hepatic fibrosis index score that is calculated using formula: FIB-4 = (Age [years] x AST [U/L]) / (platelets [10^9/L] x (square root of ALT [U/L])). A FIB-4 index of < 1.45 indicates no or moderate fibrosis and an index of > 3.25 indicates extensive fibrosis/cirrhosis. A positive change from Baseline indicates increased fibrosis.
Time Frame
Baseline and Week 12
Title
Change From Baseline to Week 12 in Fibrinogen and C Reactive Protein (CRP) Levels
Time Frame
Baseline and Week 12
Title
Change From Baseline to Week 12 in Interleukin (IL) and Tumor Necrosis Factor (TNF) Levels
Description
For IL, both IL6 and IL1β variants were analysed. For TNF, both TNF α and TNF β (also known as lymphotoxin alpha) variants were analyzed.
Time Frame
Baseline and Week 12
Title
Change From Baseline to Week 12 in Haptoglobin and Alpha2 Macroglobulin Levels
Time Frame
Baseline and Week 12
Title
Change From Baseline to Week 12 in Triglycerides (TG), Total Cholesterol (TC), High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C)
Time Frame
Baseline and Week 12
Title
Change From Baseline to Week 12 in Domain and Total Scores on the 5D-Itch Scale
Description
The 5D-Itch scale is a multidimensional questionnaire completed by participants to quantify the magnitude of pruritus, assessed considering the past 2 weeks. Scale range is 1 to 5 covering five dimensions: duration (1=Less than 6 hrs/day to 5=All day), degree (1=Not present to 5=Unbearable), direction (1=Completely resolved to 5=Getting worse), disability (for Sleep rated as 1=Never affects sleep to 5=Delays falling asleep and frequently wakes me up at night; for Leisure/Social, Housework/Errands and Work/School rated as 1=Never affects activity to 5=Always affects activity), and distribution (assess if itching is present in 16 body locations, scored as 1=present at 0-2 locations to 5=present at 14-16 locations). Total scores (including highest disability score obtained from any of the daily activities) ranged between 5 and 25 where higher scores indicated more severe itching. Negative change scores indicate improvement from the baseline score.
Time Frame
Baseline and Week 12
Title
Change From Baseline to Week 12 in Visual Analog Score (VAS) for Itching
Description
An itch VAS (0-100mm) was used to record the intensity of the event. Participants drew a line on a scale corresponding to the maximum intensity of itch. Lines drawn towards the right of the line indicated greater itching and higher scores indicated more severe itching. Negative change from baseline indicates decrease in itching.
Time Frame
Baseline to Week 12
Title
Change From Baseline to Week 12 in Domain Scores on the Primary Biliary Cholangitis-40 (PBC-40) Quality of Life (QoL) Assessment
Description
The PBC-40 is a survey measuring health related quality of life in participants with PBC. The 40 questions from the PBC-40 questionnaire are scored from 1-5, with 5 representing the highest impact and 1 the lowest impact of PBC on the quality of life. Six domains were computed from the 40 questions: symptoms (score range 7-35), itch (0-15), fatigue (11-55), cognition (6-30), social (8-50) and emotional (1-15). Higher scores indicate worse quality of life and negative change scores indicate improvement from the baseline score.
Time Frame
Baseline and Week 12
Title
Maximum Plasma Concentration (Cmax) of EDP-305 and Its Metabolites
Description
Metabolites of EDP-305 are EP-022571, EP-022572, and EP-022679.
Time Frame
Day 1 and Week 12: Pre-dose and 2, 6 and 8 hours post-dose
Title
Time to Maximum Plasma Concentration (Tmax) of EDP-305 and Its Metabolites
Description
Metabolites of EDP-305 are EP-022571, EP-022572, and EP-022679.
Time Frame
Day 1 and Week 12: Pre-dose and 2, 6 and 8 hours post-dose
Title
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of EDP-305 and Its Metabolites
Description
Metabolites of EDP-305 are EP-022571, EP-022572, and EP-022679.
Time Frame
Day 1 and Week 12: Pre-dose and 2, 6 and 8 hours post-dose
Title
Percentage Change From Baseline to Week 12 in Fibroblast Growth Factor 19 (FGF19), 7α-OH-4-cholesten-3-one (C4) and Bile Acid (BA) Concentrations
Description
FGF19 was measured in plasma. BA was measured in serum. C4 was measured in serum.
Time Frame
Baseline and Week 12
Title
Percentage Change From Baseline to Week 12 in AUC0-8 and AUC2-8 of Fibroblast Growth Factor 19 (FGF19), 7α-OH-4-cholesten-3-one (C4) and Bile Acid (BA)
Description
AUC0-8 is area under the biomarker concentration-time curve from time zero to 8 hours. AUC2-8 is area under the biomarker concentration-time curve from 2 hours to 8 hours. FGF19 was measured in plasma. BA was measured in serum. C4 was measured in serum.
Time Frame
Day 1 and Week 12: Pre-dose and 2, 6 and 8 hours post-dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
An informed consent document signed and dated by the subject.
Male and female subjects of any ethnic origin between the ages of 18 and 75 years, inclusive
Male or female with a diagnosis of PBC by at least two of the following criteria:
History of ALP above ULN for at least six months
Positive Anti-Mitochondrial Antibodies (AMA) titers (>1/40 on immunofluorescence or M2 positive by enzyme linked immunosorbent assay (ELISA) or positive PBC-specific antinuclear antibodies)
For subjects with no documented liver biopsy performed within 2 years, subjects must undergo a transient elastography (Fibroscan) showing liver stiffness < 14.0 kPA
Must be on a stable dose of UDCA12-20 mg/kg/day for at least 6 months prior to Screening or intolerant of UDCA in the opinion of the Investigator (no UDCA for at least 12 weeks prior to Screening)
Alkaline Phosphatase (ALP) ≥ 1.67 × ULN and/or total bilirubin >ULN but < 2×ULN (<2.4 mg/dL)
Subjects must have Screening laboratory values for Hepatitis B surface antigen (HBsAg), anti-HCV antibodies and HCV RNA negative and Human Immunodeficiency Virus (HIV) 1 and 2 antibodies (Ab) as seronegative. Note: subjects previously infected by chronic hepatitis C and treated with direct acting antivirals (DAAs) with sustained virologic response (SVR) for at least 3 years will be allowed.
Female subjects of childbearing potential must agree to use two effective methods of contraception from the date of Screening until 90 days after the last dose of EDP-305.
All male participants who have not had a vasectomy must use effective contraception from Day -1 to 90 days after their last dose of study drug.
Male subjects must agree to refrain from sperm donation from the date of Screening until 90 days after their last dose of study drug
Screening body mass index (BMI) of ≥18 kg/m2
Subject must be willing and able to adhere to the assessments, visit schedule, prohibitions and restrictions, as described in this protocol
Exclusion Criteria:
Laboratory Screening Results:
AST >5 x ULN
ALT >5 x ULN
Patients with Gilbert's syndrome will not be allowed due to interpretability of bilirubin levels
Total white blood cells (WBC) <3000 cells/mm3
Absolute neutrophil count (ANC) <1500 cells/mm3
Platelet count <140,000/mm3
Prothrombin time (international normalized ratio, INR) >1.2
Serum creatinine >2 mg/dL or creatinine clearance <60 mL/min (based on Cockroft-Gault Method)
Suspected to have relevant nonalcoholic fatty liver disease (NAFLD) as based on the judgment of the Investigator at Screening
Use of immunosuppressants known to have an effect on the liver of patients with PBC (eg, colchicine, methotrexate, azathioprine, or systemic steroids) in the three months preceding screening
Current use of fibrates, including fenofibrates. Note: Subjects who discontinued fibrates for at least 3 months before Screening can participate
Use of an experimental treatment for PBC within the past 6 months
Co-existing liver or biliary diseases, such as primary sclerosing cholangitis, choledocholithiasis, acute or chronic hepatitis, autoimmune hepatitis, alcoholic liver disease, nonalcoholic steatohepatitis (NASH), acute infection of bile duct system or gall bladder, history of gastrointestinal bleeding (secondary to portal hypertension), cirrhosis, cholangiocarcinoma diagnosed or suspected liver cancers
Cirrhosis with or without complications, including history or presence of: spontaneous bacterial peritonitis, hepatocellular carcinoma
Hepatorenal syndrome (type I or II) or Screening serum creatinine > 2 mg/dL (178 μmol/L)
Prior variceal hemorrhage, uncontrolled encephalopathy, Child-Pugh Class A, B and C, esophageal varices, or refractory ascites within the previous 6 months of Screening (defined as date informed consent signed)
Medical conditions that may cause nonhepatic increases in ALP (e.g., Paget's disease)
Use of a new statin regimen from Screening and throughout study duration. NOTE: Subjects on a stable dose of statins for at least 3 months prior to Screening are allowed. No dose modification during the study will be allowed.
Use of immunosuppressants (eg, systemic corticosteroids) for more than 2 consecutive weeks in duration within 1 year prior to Screening.
Facility Information:
Facility Name
Digestive Health Specialists of the Southeast
City
Dothan
State/Province
Alabama
ZIP/Postal Code
36305
Country
United States
Facility Name
Arkansas Diagnostic Center
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
Texas Clinical Research Institute
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
76012
Country
United States
Facility Name
Southern California Research Center
City
Coronado
State/Province
California
ZIP/Postal Code
92118
Country
United States
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
California Liver Research Institue
City
Pasadena
State/Province
California
ZIP/Postal Code
91105
Country
United States
Facility Name
Pasadena Liver Center
City
Pasadena
State/Province
California
ZIP/Postal Code
91105
Country
United States
Facility Name
Inland Empire Liver Foundation
City
Rialto
State/Province
California
ZIP/Postal Code
92377
Country
United States
Facility Name
California Pacific Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
South Denver Gastroenterology - Swedish Medical Center Office
City
Englewood
State/Province
Colorado
ZIP/Postal Code
80113
Country
United States
Facility Name
Yale School of Medicine
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Gastroenterology Consultants of Clearwater
City
Clearwater
State/Province
Florida
ZIP/Postal Code
33756-3839
Country
United States
Facility Name
Nature Coast Clinical Research
City
Inverness
State/Province
Florida
ZIP/Postal Code
34452
Country
United States
Facility Name
University of Miami Leonard M. Miller School of Medicine
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Consultative Gastroenterology
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30312
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University of Iowa Hospitals and Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Louisiana Research Center
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71105
Country
United States
Facility Name
Mercy Medical Center-McAuley Plaza
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21202
Country
United States
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Digestive Disease Associates
City
Catonsville
State/Province
Maryland
ZIP/Postal Code
21228
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48377
Country
United States
Facility Name
CHI Health
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68124
Country
United States
Facility Name
Dartmouth-Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
Montefiore Medical Center - Bronx
City
Bronx
State/Province
New York
ZIP/Postal Code
10461-1925
Country
United States
Facility Name
Northwell Health
City
Manhasset
State/Province
New York
ZIP/Postal Code
11030
Country
United States
Facility Name
Concorde Medical Group
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Mount Sinai Beth Isreal
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Weill Cornell Medical College
City
New York
State/Province
New York
ZIP/Postal Code
10024
Country
United States
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
University of Pittsburgh Medical Center - Center for Liver Disease
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
The Liver Institute at Methodist Dallas Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75203
Country
United States
Facility Name
Liver Consultants of Texas
City
Dallas
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Baylor Saint Luke's Medical Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
American Research Corporation at the Texas Liver Institute
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
Facility Name
Liver Institute of Virginia-Bremo
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23602
Country
United States
Facility Name
Swedish First Hill Campus
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195-6460
Country
United States
Facility Name
Nepean Hospital
City
Kingswood
State/Province
New South Wales
ZIP/Postal Code
2747
Country
Australia
Facility Name
Monash Medical Centre
City
Clayton
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
Facility Name
Linear Clinical Research
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6000
Country
Australia
Facility Name
Klinikum Klagenfurt Am Wörthersee
City
Klagenfurt am Wörthersee
State/Province
Carinthia
ZIP/Postal Code
9020
Country
Austria
Facility Name
Medizinische Universität Innsbruck
City
Innsbruck
State/Province
Tyrol
ZIP/Postal Code
6020
Country
Austria
Facility Name
Klinikum Wels-Grieskirchen
City
Wels
State/Province
Upper Austria
ZIP/Postal Code
4600
Country
Austria
Facility Name
CHU de Liège, Cardiology Dept.
City
Liège
State/Province
Liege
ZIP/Postal Code
4000
Country
Belgium
Facility Name
Ziekenhuis Oost-Limburg
City
Genk
State/Province
Limburg
ZIP/Postal Code
3600
Country
Belgium
Facility Name
Universitair Ziekenhuis Gent
City
Gent
State/Province
Oost-vlaanderen
ZIP/Postal Code
9000
Country
Belgium
Facility Name
London Health Sciences Centre University Hospital
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5A5
Country
Canada
Facility Name
Toronto General Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada
Facility Name
Toronto Liver Center
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M6H 3M1
Country
Canada
Facility Name
Nouvel Hôpital Civil
City
Strasbourg cedex
State/Province
Alsace
ZIP/Postal Code
67091
Country
France
Facility Name
Hôpital Haut-Lévêque
City
Pessac
State/Province
Aquitaine
ZIP/Postal Code
33600
Country
France
Facility Name
Hôpital Saint-Antoine
City
Paris Cedex 12
State/Province
Ile-de-france
ZIP/Postal Code
75012
Country
France
Facility Name
Hôpital Paul Brousse
City
Villejuif Cedex
State/Province
Ile-de-france
ZIP/Postal Code
94800
Country
France
Facility Name
Hôpital Saint-Eloi
City
Montpellier cedex 5
State/Province
Languedoc-roussillon
ZIP/Postal Code
34295
Country
France
Facility Name
Centre Hospitalier Régional Universitaire de Lille
City
Lille
State/Province
NORD Pas-de-calais
ZIP/Postal Code
59037
Country
France
Facility Name
Centre Hospitalier Universitaire Amines-Picardie Hôpital Sud
City
Amiens Cedex 1
State/Province
Picardie
ZIP/Postal Code
80054
Country
France
Facility Name
Hôpital de la Croix Rousse
City
Lyon Cedex 04
State/Province
Rhone-alpes
ZIP/Postal Code
69317
Country
France
Facility Name
Universitätsklinikum Würzburg
City
Würzburg
State/Province
Bayern
ZIP/Postal Code
97080
Country
Germany
Facility Name
Universitätsklinikum Frankfurt
City
Frankfurt am Main
State/Province
Hessen
ZIP/Postal Code
60590
Country
Germany
Facility Name
Universitätsklinikum Bonn
City
Bonn
State/Province
Nordrhein-westfalen
ZIP/Postal Code
53127
Country
Germany
Facility Name
Universitaetsklinikum Essen
City
Essen
State/Province
Nordrhein-westfalen
ZIP/Postal Code
45122
Country
Germany
Facility Name
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
City
Mainz
State/Province
Rheinland-pfalz
ZIP/Postal Code
55131
Country
Germany
Facility Name
Universitätsklinikum Leipzig
City
Leipzig
State/Province
Sachsen
ZIP/Postal Code
04103
Country
Germany
Facility Name
Charité Universitätsmedizin Berlin
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Vrije Universiteit Medisch Centrum
City
Amsterdam
State/Province
Noord-holland
ZIP/Postal Code
1081 HV
Country
Netherlands
Facility Name
Leiden Universitair Medisch Centrum
City
Leiden
State/Province
Zuid-holland
ZIP/Postal Code
2333 ZA
Country
Netherlands
Facility Name
Universitair Medisch Centrum Utrecht
City
Utrecht
ZIP/Postal Code
3584 CX
Country
Netherlands
Facility Name
Hospital Universitario Donostia
City
San Sebastian
State/Province
Guipuzcoa
ZIP/Postal Code
20014
Country
Spain
Facility Name
Hospital Universitario Virgen de la Arrixaca
City
El Palmar
State/Province
Murcia
ZIP/Postal Code
30120
Country
Spain
Facility Name
Hospital Universitari Vall d'Hebrón
City
Barcelona
ZIP/Postal Code
08029
Country
Spain
Facility Name
Hospital Universitario Ramón Y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Hospital Universitario Marqués de Valdecilla
City
Santander
ZIP/Postal Code
39008
Country
Spain
Facility Name
Hospital Universitario Virgen del Rocio
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
Hospital Universitari i Politecnic La Fe de Valencia
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Facility Name
Universidad de Valladolid - Hospital Universitario Rio Hortega
City
Valladolid
ZIP/Postal Code
47010
Country
Spain
Facility Name
University Hospitals Birmingham NHS Foundation Trust
City
Birmingham
State/Province
England
ZIP/Postal Code
B15 2TT
Country
United Kingdom
Facility Name
Cambridge University Hospitals NHS Foundation Trust
City
Cambridge
State/Province
England
ZIP/Postal Code
CB2 0QQ
Country
United Kingdom
Facility Name
The Leeds Teaching Hospitals NHS Trust
City
Leeds
State/Province
England
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Facility Name
King's College Hospital NHS Foundation Trust
City
London
State/Province
England
ZIP/Postal Code
SE5 9RS
Country
United Kingdom
Facility Name
Norfolk and Norwich University Hospitals NHS Foundation Trust
City
Norwich
State/Province
England
ZIP/Postal Code
NR4 7UY
Country
United Kingdom
Facility Name
Queen's Medical Centre - Nottingham
City
Nottingham
State/Province
England
ZIP/Postal Code
NG7 2UH
Country
United Kingdom
Facility Name
Portsmouth Hospitals NHS Trust
City
Portsmouth
State/Province
England
ZIP/Postal Code
PO6 3LY
Country
United Kingdom
Facility Name
NHS Lothian
City
Edinburgh
State/Province
Scotland
ZIP/Postal Code
EH16 4SA
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of EDP-305 in Subjects With Primary Biliary Cholangitis
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