Primary Biliary Cholangitis
Conditions
Keywords
PBC, Primary Biliary Cholangitis (PBC)
Brief summary
A randomized, double-blind study to assess the safety, tolerability, PK and efficacy of EDP-305 in subjects with primary biliary cholangitis
Interventions
DRUGEDP-305 1 mg
Two tablets daily for 12 weeks
DRUGEDP-305 2.5 mg
Two tablets daily for 12 weeks
DRUGPlacebo
Two tablets daily for 12 weeks
Sponsors
Pharmaceutical Research Associates
Triangle Biostatistics, LLC
Enanta Pharmaceuticals, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With At Least a 20% Reduction in Alkaline Phosphatase (ALP) or Normalization of ALP at Week 12 Compared to Baseline | Baseline and Week 12 | 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
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Treatment-Emergent Serious Adverse Event (SAE) During On-Treatment Period | Up to approximately Week 12 | 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 | Up to approximately Week 12 | 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 | Baseline and Week 12 | 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) | Baseline and Week 12 | — |
| 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) | Baseline and Week 12 | 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 | Baseline and Week 12 | 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 | Baseline and Week 12 | 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 | Baseline and Week 12 | — |
| Change From Baseline to Week 12 in Interleukin (IL) and Tumor Necrosis Factor (TNF) Levels | Baseline and Week 12 | 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. |
| Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE) During On-Treatment Period | Up to approximately Week 12 | 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 Triglycerides (TG), Total Cholesterol (TC), High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C) | Baseline and Week 12 | — |
| Change From Baseline to Week 12 in Domain and Total Scores on the 5D-Itch Scale | Baseline and Week 12 | 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 | Baseline to Week 12 | 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. |
| 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 | Day 1 and Week 12: Pre-dose and 2, 6 and 8 hours post-dose | Metabolites of EDP-305 are EP-022571, EP-022572, and EP-022679. |
| Change From Baseline to Week 12 in Domain Scores on the Primary Biliary Cholangitis-40 (PBC-40) Quality of Life (QoL) Assessment | Baseline and Week 12 | 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 | Day 1 and Week 12: Pre-dose and 2, 6 and 8 hours post-dose | Metabolites of EDP-305 are EP-022571, EP-022572, and EP-022679. |
| Time to Maximum Plasma Concentration (Tmax) of EDP-305 and Its Metabolites | Day 1 and Week 12: Pre-dose and 2, 6 and 8 hours post-dose | 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 | Baseline and Week 12 | 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) | Day 1 and Week 12: Pre-dose and 2, 6 and 8 hours post-dose | 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. |
| Change From Baseline to Week 12 in Haptoglobin and Alpha2 Macroglobulin Levels | Baseline and Week 12 | — |
Countries
Australia, Austria, Belgium, Canada, France, Germany, Netherlands, Spain, United Kingdom, United States
Participant flow
Recruitment details
The trial included 68 participants from 43 sites in Australia, Canada, Europe and the United States from December 2017 to January 2020.
Pre-assignment details
132 participants were screened, 64 of which were screen failures. The remaining 68 were enrolled and received trial treatment.
Participants by arm
| Arm | Count |
|---|---|
| EDP-305 1 mg Participants took EDP-305 1 mg as an oral tablet once daily for 12 weeks. | 31 |
| EDP-305 2.5 mg Participants took EDP-305 2.5 mg as an oral tablet once daily for 12 weeks. | 28 |
| Placebo Participants received an oral placebo matching EDP-305 once daily for 12 weeks. | 9 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 5 | 0 |
| Overall Study | Did not meet all inclusion criteria | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | EDP-305 1 mg | EDP-305 2.5 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 57.4 years STANDARD_DEVIATION 8.61 | 54.9 years STANDARD_DEVIATION 10.92 | 56.9 years STANDARD_DEVIATION 8.49 | 56.3 years STANDARD_DEVIATION 9.55 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 2 Participants | 0 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants | 25 Participants | 9 Participants | 61 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized All other races | 3 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 28 Participants | 27 Participants | 9 Participants | 64 Participants |
| Region of Enrollment Australia | 2 participants | 1 participants | 2 participants | 5 participants |
| Region of Enrollment Austria | 0 participants | 2 participants | 0 participants | 2 participants |
| Region of Enrollment Belgium | 0 participants | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Canada | 1 participants | 1 participants | 1 participants | 3 participants |
| Region of Enrollment France | 0 participants | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Germany | 2 participants | 1 participants | 1 participants | 4 participants |
| Region of Enrollment Netherlands | 1 participants | 1 participants | 0 participants | 2 participants |
| Region of Enrollment Spain | 3 participants | 2 participants | 2 participants | 7 participants |
| Region of Enrollment United Kingdom | 6 participants | 6 participants | 1 participants | 13 participants |
| Region of Enrollment United States | 16 participants | 12 participants | 2 participants | 30 participants |
| Sex: Female, Male Female | 31 Participants | 27 Participants | 9 Participants | 67 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 28 | 0 / 9 |
| other Total, other adverse events | 23 / 31 | 24 / 28 | 8 / 9 |
| serious Total, serious adverse events | 1 / 31 | 2 / 28 | 0 / 9 |
Outcome results
Primary
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.
Time frame: Baseline and Week 12
Population: Full Efficacy Population: All subjects who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EDP-305 1 mg | Percentage of Participants With At Least a 20% Reduction in Alkaline Phosphatase (ALP) or Normalization of ALP at Week 12 Compared to Baseline | 45.2 percentage of participants |
| EDP-305 2.5 mg | Percentage of Participants With At Least a 20% Reduction in Alkaline Phosphatase (ALP) or Normalization of ALP at Week 12 Compared to Baseline | 46.4 percentage of participants |
| Placebo | Percentage of Participants With At Least a 20% Reduction in Alkaline Phosphatase (ALP) or Normalization of ALP at Week 12 Compared to Baseline | 11.1 percentage of participants |
p-value: 0.10695% CI: [0.6, 52]Cochran-Mantel-Haenszel
p-value: 0.06395% CI: [0.75, 65.22]Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Day 1 and Week 12: Pre-dose and 2, 6 and 8 hours post-dose
Population: Blood samples for Pharmacokinetic (PK) analysis were collected from a subset of study sites and included participants who received active study drug and had any measurable plasma concentration of study drug at any timepoint. Results are presented for participants that have data available for analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| EDP-305 1 mg | 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 | EDP-305 Day 1 | 85.50 h*ng/mL | Geometric Coefficient of Variation 51.57 |
| EDP-305 1 mg | 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 | EDP-305 Week 12 | 67.60 h*ng/mL | Geometric Coefficient of Variation 75.47 |
| EDP-305 1 mg | 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 | EP-022571 Day 1 | 2.30 h*ng/mL | Geometric Coefficient of Variation 37.32 |
| EDP-305 1 mg | 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 | EP-022571 Week 12 | 0.90 h*ng/mL | Geometric Coefficient of Variation 78.75 |
| EDP-305 1 mg | 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 | EP-022572 Day 1 | 2.50 h*ng/mL | Geometric Coefficient of Variation 32.37 |
| EDP-305 1 mg | 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 | EP-022572 Week 12 | 1.20 h*ng/mL | Geometric Coefficient of Variation 53.12 |
| EDP-305 1 mg | 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 | EP-022679 Day 1 | 3.70 h*ng/mL | Geometric Coefficient of Variation 109.3 |
| EDP-305 1 mg | 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 | EP-022679 Week 12 | 3.00 h*ng/mL | Geometric Coefficient of Variation 203.04 |
| EDP-305 2.5 mg | 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 | EP-022679 Week 12 | 57.00 h*ng/mL | Geometric Coefficient of Variation 343.47 |
| EDP-305 2.5 mg | 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 | EDP-305 Day 1 | 95.30 h*ng/mL | Geometric Coefficient of Variation 141.72 |
| EDP-305 2.5 mg | 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 | EP-022572 Day 1 | 2.90 h*ng/mL | Geometric Coefficient of Variation 96.7 |
| EDP-305 2.5 mg | 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 | EDP-305 Week 12 | 316.20 h*ng/mL | Geometric Coefficient of Variation 42.34 |
| EDP-305 2.5 mg | 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 | EP-022679 Day 1 | 5.00 h*ng/mL | Geometric Coefficient of Variation 305.62 |
| EDP-305 2.5 mg | 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 | EP-022571 Day 1 | 2.00 h*ng/mL | Geometric Coefficient of Variation 132.47 |
| EDP-305 2.5 mg | 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 | EP-022572 Week 12 | 10.10 h*ng/mL | Geometric Coefficient of Variation 148.55 |
| EDP-305 2.5 mg | 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 | EP-022571 Week 12 | 7.30 h*ng/mL | Geometric Coefficient of Variation 154.62 |
Secondary
Change From Baseline to Week 12 in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT)
Time frame: Baseline and Week 12
Population: Results are presented for participants from the Full Efficacy Population that have data available for analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| EDP-305 1 mg | Change From Baseline to Week 12 in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) | AST | -12.08 U/L |
| EDP-305 1 mg | Change From Baseline to Week 12 in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) | ALT | -17.35 U/L |
| EDP-305 1 mg | Change From Baseline to Week 12 in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) | GGT | -95.91 U/L |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) | AST | -11.51 U/L |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) | ALT | -13.14 U/L |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) | GGT | -124.55 U/L |
| Placebo | Change From Baseline to Week 12 in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) | ALT | 8.20 U/L |
| Placebo | Change From Baseline to Week 12 in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) | GGT | -9.42 U/L |
| Placebo | Change From Baseline to Week 12 in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) | AST | 9.33 U/L |
Comparison: Analysis for ALT.p-value: 0.00195% CI: [-40.07, -11.04]ANCOVA
Comparison: Analysis for ALT.p-value: 0.00995% CI: [-37.1, -5.6]ANCOVA
Comparison: Analysis for AST.p-value: 095% CI: [-32.48, -10.35]ANCOVA
Comparison: Analysis for AST.p-value: 0.00195% CI: [-32.8, -8.87]ANCOVA
Comparison: Analysis for GGT.p-value: 095% CI: [-123.78, -49.21]ANCOVA
Comparison: Analysis for GGT.p-value: 095% CI: [-155.04, -75.22]ANCOVA
Secondary
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.
Time frame: Baseline and Week 12
Population: Results are presented for participants from the Full Efficacy Population that have data available for analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| EDP-305 1 mg | Change From Baseline to Week 12 in Domain and Total Scores on the 5D-Itch Scale | Duration | 0.01 Scores on a scale |
| EDP-305 1 mg | Change From Baseline to Week 12 in Domain and Total Scores on the 5D-Itch Scale | Degree | 0.00 Scores on a scale |
| EDP-305 1 mg | Change From Baseline to Week 12 in Domain and Total Scores on the 5D-Itch Scale | Direction | -0.63 Scores on a scale |
| EDP-305 1 mg | Change From Baseline to Week 12 in Domain and Total Scores on the 5D-Itch Scale | Disability | -0.24 Scores on a scale |
| EDP-305 1 mg | Change From Baseline to Week 12 in Domain and Total Scores on the 5D-Itch Scale | Distribution | 0.07 Scores on a scale |
| EDP-305 1 mg | Change From Baseline to Week 12 in Domain and Total Scores on the 5D-Itch Scale | Total | -0.95 Scores on a scale |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Domain and Total Scores on the 5D-Itch Scale | Total | 3.19 Scores on a scale |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Domain and Total Scores on the 5D-Itch Scale | Duration | 0.41 Scores on a scale |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Domain and Total Scores on the 5D-Itch Scale | Disability | 0.85 Scores on a scale |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Domain and Total Scores on the 5D-Itch Scale | Distribution | 0.81 Scores on a scale |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Domain and Total Scores on the 5D-Itch Scale | Degree | 0.65 Scores on a scale |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Domain and Total Scores on the 5D-Itch Scale | Direction | 0.36 Scores on a scale |
| Placebo | Change From Baseline to Week 12 in Domain and Total Scores on the 5D-Itch Scale | Degree | -0.53 Scores on a scale |
| Placebo | Change From Baseline to Week 12 in Domain and Total Scores on the 5D-Itch Scale | Direction | -0.65 Scores on a scale |
| Placebo | Change From Baseline to Week 12 in Domain and Total Scores on the 5D-Itch Scale | Total | -3.16 Scores on a scale |
| Placebo | Change From Baseline to Week 12 in Domain and Total Scores on the 5D-Itch Scale | Disability | -0.61 Scores on a scale |
| Placebo | Change From Baseline to Week 12 in Domain and Total Scores on the 5D-Itch Scale | Duration | -0.24 Scores on a scale |
| Placebo | Change From Baseline to Week 12 in Domain and Total Scores on the 5D-Itch Scale | Distribution | -0.42 Scores on a scale |
Comparison: Analysis for disability.p-value: 095% CI: [0.67, 2.26]ANCOVA
Comparison: Analysis for distribution.p-value: 0.21495% CI: [-0.29, 1.25]ANCOVA
Comparison: Analysis for distribution.p-value: 0.00395% CI: [0.44, 2.02]ANCOVA
Comparison: Analysis for duration.p-value: 0.37895% CI: [-0.32, 0.82]ANCOVA
Comparison: Analysis for duration.p-value: 0.0395% CI: [0.07, 1.23]ANCOVA
Comparison: Analysis for degree.p-value: 0.03695% CI: [0.04, 1.03]ANCOVA
Comparison: Analysis for degree.p-value: 095% CI: [0.67, 1.69]ANCOVA
Comparison: Analysis for direction.p-value: 0.97195% CI: [-0.92, 0.96]ANCOVA
Comparison: Analysis for direction.p-value: 0.04295% CI: [0.04, 1.99]ANCOVA
Comparison: Analysis for disability.p-value: 0.33695% CI: [-0.4, 1.14]ANCOVA
Comparison: Analysis for total.p-value: 0.10395% CI: [-0.47, 4.9]ANCOVA
Comparison: Analysis for total.p-value: 095% CI: [3.57, 9.13]ANCOVA
Secondary
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.
Time frame: Baseline and Week 12
Population: Results are presented for participants from the Full Efficacy Population that have data available for analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| EDP-305 1 mg | Change From Baseline to Week 12 in Domain Scores on the Primary Biliary Cholangitis-40 (PBC-40) Quality of Life (QoL) Assessment | Symptoms | -0.21 Scores on a scale |
| EDP-305 1 mg | Change From Baseline to Week 12 in Domain Scores on the Primary Biliary Cholangitis-40 (PBC-40) Quality of Life (QoL) Assessment | Itch | 0.18 Scores on a scale |
| EDP-305 1 mg | Change From Baseline to Week 12 in Domain Scores on the Primary Biliary Cholangitis-40 (PBC-40) Quality of Life (QoL) Assessment | Fatigue | -0.36 Scores on a scale |
| EDP-305 1 mg | Change From Baseline to Week 12 in Domain Scores on the Primary Biliary Cholangitis-40 (PBC-40) Quality of Life (QoL) Assessment | Cognition | -0.21 Scores on a scale |
| EDP-305 1 mg | Change From Baseline to Week 12 in Domain Scores on the Primary Biliary Cholangitis-40 (PBC-40) Quality of Life (QoL) Assessment | Social | -0.38 Scores on a scale |
| EDP-305 1 mg | Change From Baseline to Week 12 in Domain Scores on the Primary Biliary Cholangitis-40 (PBC-40) Quality of Life (QoL) Assessment | Emotional | -0.77 Scores on a scale |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Domain Scores on the Primary Biliary Cholangitis-40 (PBC-40) Quality of Life (QoL) Assessment | Emotional | 0.23 Scores on a scale |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Domain Scores on the Primary Biliary Cholangitis-40 (PBC-40) Quality of Life (QoL) Assessment | Symptoms | -1.46 Scores on a scale |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Domain Scores on the Primary Biliary Cholangitis-40 (PBC-40) Quality of Life (QoL) Assessment | Cognition | 0.82 Scores on a scale |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Domain Scores on the Primary Biliary Cholangitis-40 (PBC-40) Quality of Life (QoL) Assessment | Social | 0.96 Scores on a scale |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Domain Scores on the Primary Biliary Cholangitis-40 (PBC-40) Quality of Life (QoL) Assessment | Itch | 1.74 Scores on a scale |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Domain Scores on the Primary Biliary Cholangitis-40 (PBC-40) Quality of Life (QoL) Assessment | Fatigue | -0.22 Scores on a scale |
| Placebo | Change From Baseline to Week 12 in Domain Scores on the Primary Biliary Cholangitis-40 (PBC-40) Quality of Life (QoL) Assessment | Itch | -1.73 Scores on a scale |
| Placebo | Change From Baseline to Week 12 in Domain Scores on the Primary Biliary Cholangitis-40 (PBC-40) Quality of Life (QoL) Assessment | Fatigue | 0.10 Scores on a scale |
| Placebo | Change From Baseline to Week 12 in Domain Scores on the Primary Biliary Cholangitis-40 (PBC-40) Quality of Life (QoL) Assessment | Emotional | -0.15 Scores on a scale |
| Placebo | Change From Baseline to Week 12 in Domain Scores on the Primary Biliary Cholangitis-40 (PBC-40) Quality of Life (QoL) Assessment | Cognition | -0.48 Scores on a scale |
| Placebo | Change From Baseline to Week 12 in Domain Scores on the Primary Biliary Cholangitis-40 (PBC-40) Quality of Life (QoL) Assessment | Symptoms | -0.06 Scores on a scale |
| Placebo | Change From Baseline to Week 12 in Domain Scores on the Primary Biliary Cholangitis-40 (PBC-40) Quality of Life (QoL) Assessment | Social | 1.73 Scores on a scale |
Comparison: Analysis for symptoms.p-value: 0.90895% CI: [-2.72, 2.43]ANCOVA
Comparison: Analysis for symptoms.p-value: 0.29895% CI: [-4.09, 1.27]ANCOVA
Comparison: Analysis for itch.p-value: 0.04295% CI: [0.07, 3.76]ANCOVA
Comparison: Analysis for itch.p-value: 0.00195% CI: [1.55, 5.38]ANCOVA
Comparison: Analysis for fatigue.p-value: 0.83995% CI: [-4.96, 4.04]ANCOVA
Comparison: Analysis for fatigue.p-value: 0.89195% CI: [-5, 4.36]ANCOVA
Comparison: Analysis for cognition.p-value: 0.83495% CI: [-2.25, 2.77]ANCOVA
Comparison: Analysis for cognition.p-value: 0.32795% CI: [-1.33, 3.92]ANCOVA
Comparison: Analysis for social.p-value: 0.26295% CI: [-5.86, 1.62]ANCOVA
Comparison: Analysis for social.p-value: 0.6995% CI: [-4.68, 3.12]ANCOVA
Comparison: Analysis for emotional.p-value: 0.43395% CI: [-2.19, 0.95]ANCOVA
Comparison: Analysis for emotional.p-value: 0.65395% CI: [-1.28, 2.03]ANCOVA
Secondary
Change From Baseline to Week 12 in Fibrinogen and C Reactive Protein (CRP) Levels
Time frame: Baseline and Week 12
Population: Results are presented for participants from the Full Efficacy Population that have data available for analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| EDP-305 1 mg | Change From Baseline to Week 12 in Fibrinogen and C Reactive Protein (CRP) Levels | Fibrinogen | 16.28 mg/dL |
| EDP-305 1 mg | Change From Baseline to Week 12 in Fibrinogen and C Reactive Protein (CRP) Levels | CRP | -0.57 mg/dL |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Fibrinogen and C Reactive Protein (CRP) Levels | Fibrinogen | 41.25 mg/dL |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Fibrinogen and C Reactive Protein (CRP) Levels | CRP | -2.69 mg/dL |
| Placebo | Change From Baseline to Week 12 in Fibrinogen and C Reactive Protein (CRP) Levels | Fibrinogen | 9.47 mg/dL |
| Placebo | Change From Baseline to Week 12 in Fibrinogen and C Reactive Protein (CRP) Levels | CRP | 0.41 mg/dL |
Comparison: Analysis for fibrinogen.p-value: 0.75795% CI: [-37.17, 50.78]ANCOVA
Comparison: Analysis for fibrinogen.p-value: 0.17495% CI: [-14.42, 77.97]ANCOVA
Comparison: Analysis for CRP.p-value: 0.37895% CI: [-3.18, 1.23]ANCOVA
Comparison: Analysis for CRP.p-value: 0.00895% CI: [-5.38, -0.83]ANCOVA
Secondary
Change From Baseline to Week 12 in Haptoglobin and Alpha2 Macroglobulin Levels
Time frame: Baseline and Week 12
Population: Results are presented for participants from the Full Efficacy Population that have data available for analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| EDP-305 1 mg | Change From Baseline to Week 12 in Haptoglobin and Alpha2 Macroglobulin Levels | Haptoglobin | -0.14 g/L |
| EDP-305 1 mg | Change From Baseline to Week 12 in Haptoglobin and Alpha2 Macroglobulin Levels | Alpha2 Macroglobulin | -0.02 g/L |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Haptoglobin and Alpha2 Macroglobulin Levels | Haptoglobin | -0.18 g/L |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Haptoglobin and Alpha2 Macroglobulin Levels | Alpha2 Macroglobulin | -0.00 g/L |
| Placebo | Change From Baseline to Week 12 in Haptoglobin and Alpha2 Macroglobulin Levels | Haptoglobin | -0.15 g/L |
| Placebo | Change From Baseline to Week 12 in Haptoglobin and Alpha2 Macroglobulin Levels | Alpha2 Macroglobulin | 0.02 g/L |
Comparison: Analysis for haptoglobin.p-value: 0.94495% CI: [-0.25, 0.27]ANCOVA
Comparison: Analysis for haptoglobin.p-value: 0.8395% CI: [-0.3, 0.24]ANCOVA
Comparison: Analysis for alpha2 macroglobulin.p-value: 0.54695% CI: [-0.19, 0.1]ANCOVA
Comparison: Analysis for alpha2 macroglobulin.p-value: 0.78595% CI: [-0.18, 0.13]ANCOVA
Secondary
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.
Time frame: Baseline and Week 12
Population: Results are presented for participants from the Full Efficacy Population that have data available for analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| EDP-305 1 mg | Change From Baseline to Week 12 in Interleukin (IL) and Tumor Necrosis Factor (TNF) Levels | IL6 | 0.73 ng/L |
| EDP-305 1 mg | Change From Baseline to Week 12 in Interleukin (IL) and Tumor Necrosis Factor (TNF) Levels | IL1β | NA ng/L |
| EDP-305 1 mg | Change From Baseline to Week 12 in Interleukin (IL) and Tumor Necrosis Factor (TNF) Levels | TNF α | -0.15 ng/L |
| EDP-305 1 mg | Change From Baseline to Week 12 in Interleukin (IL) and Tumor Necrosis Factor (TNF) Levels | TNF β | NA ng/L |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Interleukin (IL) and Tumor Necrosis Factor (TNF) Levels | TNF β | NA ng/L |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Interleukin (IL) and Tumor Necrosis Factor (TNF) Levels | IL6 | -2.10 ng/L |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Interleukin (IL) and Tumor Necrosis Factor (TNF) Levels | TNF α | -0.01 ng/L |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Interleukin (IL) and Tumor Necrosis Factor (TNF) Levels | IL1β | NA ng/L |
| Placebo | Change From Baseline to Week 12 in Interleukin (IL) and Tumor Necrosis Factor (TNF) Levels | TNF β | NA ng/L |
| Placebo | Change From Baseline to Week 12 in Interleukin (IL) and Tumor Necrosis Factor (TNF) Levels | IL1β | NA ng/L |
| Placebo | Change From Baseline to Week 12 in Interleukin (IL) and Tumor Necrosis Factor (TNF) Levels | TNF α | 0.39 ng/L |
| Placebo | Change From Baseline to Week 12 in Interleukin (IL) and Tumor Necrosis Factor (TNF) Levels | IL6 | 0.39 ng/L |
Comparison: Analysis for IL6.p-value: 0.84195% CI: [-3.07, 3.76]ANCOVA
Comparison: Analysis for IL6.p-value: 0.16395% CI: [-6.01, 1.04]ANCOVA
Comparison: Analysis for TNF α.p-value: 0.0395% CI: [-1.02, -0.05]ANCOVA
Comparison: Analysis for TNF α.p-value: 0.1195% CI: [-0.9, 0.09]ANCOVA
Secondary
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.
Time frame: Baseline and Week 12
Population: Results are presented for participants from the Full Efficacy Population that have data available for analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| EDP-305 1 mg | Change From Baseline to Week 12 in Noninvasive Liver Fibrosis Markers: AST to Platelet Ratio Index (APRI) Score | -0.16 Index |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Noninvasive Liver Fibrosis Markers: AST to Platelet Ratio Index (APRI) Score | -0.12 Index |
| Placebo | Change From Baseline to Week 12 in Noninvasive Liver Fibrosis Markers: AST to Platelet Ratio Index (APRI) Score | 0.22 Index |
p-value: 095% CI: [-0.56, -0.18]ANCOVA
p-value: 0.00295% CI: [-0.54, -0.13]ANCOVA
Secondary
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.
Time frame: Baseline and Week 12
Population: Results are presented for participants from the Full Efficacy Population that have data available for analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| EDP-305 1 mg | 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) | HA | 1.17 μg/L |
| EDP-305 1 mg | 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) | PIIINP | -0.08 μg/L |
| EDP-305 1 mg | 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) | TIMP 1 | -16.29 μg/L |
| EDP-305 1 mg | 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) | PRO C3 | -0.67 μg/L |
| EDP-305 2.5 mg | 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) | PRO C3 | 2.33 μg/L |
| EDP-305 2.5 mg | 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) | HA | -1.16 μg/L |
| EDP-305 2.5 mg | 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) | TIMP 1 | -20.90 μg/L |
| EDP-305 2.5 mg | 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) | PIIINP | -0.77 μg/L |
| Placebo | 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) | PRO C3 | 9.06 μg/L |
| Placebo | 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) | PIIINP | 3.01 μg/L |
| Placebo | 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) | TIMP 1 | 25.66 μg/L |
| Placebo | 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) | HA | 27.83 μg/L |
Comparison: Analysis for HA.p-value: 0.14895% CI: [-63.1, 9.79]ANCOVA
Comparison: Analysis for HA.p-value: 0.14295% CI: [-68.02, 10.05]ANCOVA
Comparison: Analysis for PIIINP.p-value: 0.0295% CI: [-5.68, -0.51]ANCOVA
Comparison: Analysis for PIIINP.p-value: 0.00995% CI: [-6.6, -0.97]ANCOVA
Comparison: Analysis for TIMP 1.p-value: 0.01595% CI: [-75.47, -8.44]ANCOVA
Comparison: Analysis for TIMP 1.p-value: 0.01195% CI: [-81.91, -11.21]ANCOVA
Comparison: Analysis for PRO C3.p-value: 0.01895% CI: [-17.7, -1.75]ANCOVA
Comparison: Analysis for PRO C3.p-value: 0.12595% CI: [-15.41, 1.95]ANCOVA
Secondary
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.
Time frame: Baseline and Week 12
Population: Results are presented for participants from the Full Efficacy Population that have data available for analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| EDP-305 1 mg | Change From Baseline to Week 12 in Noninvasive Liver Fibrosis Markers: Fibrosis-4 (FIB-4) Score | -0.14 Index |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Noninvasive Liver Fibrosis Markers: Fibrosis-4 (FIB-4) Score | -0.05 Index |
| Placebo | Change From Baseline to Week 12 in Noninvasive Liver Fibrosis Markers: Fibrosis-4 (FIB-4) Score | 0.21 Index |
p-value: 0.02695% CI: [-0.65, -0.04]ANCOVA
p-value: 0.10495% CI: [-0.57, 0.05]ANCOVA
Secondary
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.
Time frame: Baseline and Week 12
Population: Results are presented for participants from the Full Efficacy Population that have data available for analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| EDP-305 1 mg | Change From Baseline to Week 12 in Total, Conjugated and Unconjugated Bilirubin | Conjugated | -0.55 μmol/L |
| EDP-305 1 mg | Change From Baseline to Week 12 in Total, Conjugated and Unconjugated Bilirubin | Total | -0.04 μmol/L |
| EDP-305 1 mg | Change From Baseline to Week 12 in Total, Conjugated and Unconjugated Bilirubin | Unconjugated | 0.71 μmol/L |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Total, Conjugated and Unconjugated Bilirubin | Conjugated | -0.51 μmol/L |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Total, Conjugated and Unconjugated Bilirubin | Total | -0.31 μmol/L |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Total, Conjugated and Unconjugated Bilirubin | Unconjugated | 0.22 μmol/L |
| Placebo | Change From Baseline to Week 12 in Total, Conjugated and Unconjugated Bilirubin | Total | -0.50 μmol/L |
| Placebo | Change From Baseline to Week 12 in Total, Conjugated and Unconjugated Bilirubin | Unconjugated | -0.50 μmol/L |
| Placebo | Change From Baseline to Week 12 in Total, Conjugated and Unconjugated Bilirubin | Conjugated | 0.13 μmol/L |
Comparison: Analysis for total bilirubin.p-value: 0.61695% CI: [-1.39, 2.32]ANCOVA
Comparison: Analysis for total bilirubin.p-value: 0.84495% CI: [-1.78, 2.16]ANCOVA
Comparison: Analysis for conjugated bilirubin.p-value: 0.1895% CI: [-1.67, 0.32]ANCOVA
Comparison: Analysis for conjugated bilirubin.p-value: 0.23995% CI: [-1.71, 0.44]ANCOVA
Comparison: Analysis for unconjugated bilirubin.p-value: 0.11695% CI: [-0.31, 2.73]ANCOVA
Comparison: Analysis for unconjugated bilirubin.p-value: 0.3695% CI: [-0.84, 2.28]ANCOVA
Secondary
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
Population: Results are presented for participants from the Full Efficacy Population that have data available for analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| EDP-305 1 mg | Change From Baseline to Week 12 in Triglycerides (TG), Total Cholesterol (TC), High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C) | TG | -0.13 mmol/L |
| EDP-305 1 mg | Change From Baseline to Week 12 in Triglycerides (TG), Total Cholesterol (TC), High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C) | TC | -0.47 mmol/L |
| EDP-305 1 mg | Change From Baseline to Week 12 in Triglycerides (TG), Total Cholesterol (TC), High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C) | HDL-C | -0.16 mmol/L |
| EDP-305 1 mg | Change From Baseline to Week 12 in Triglycerides (TG), Total Cholesterol (TC), High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C) | LDL-C | -0.21 mmol/L |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Triglycerides (TG), Total Cholesterol (TC), High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C) | LDL-C | -0.01 mmol/L |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Triglycerides (TG), Total Cholesterol (TC), High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C) | TG | 0.01 mmol/L |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Triglycerides (TG), Total Cholesterol (TC), High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C) | HDL-C | -0.46 mmol/L |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Triglycerides (TG), Total Cholesterol (TC), High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C) | TC | -0.46 mmol/L |
| Placebo | Change From Baseline to Week 12 in Triglycerides (TG), Total Cholesterol (TC), High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C) | LDL-C | 0.29 mmol/L |
| Placebo | Change From Baseline to Week 12 in Triglycerides (TG), Total Cholesterol (TC), High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C) | TC | 0.17 mmol/L |
| Placebo | Change From Baseline to Week 12 in Triglycerides (TG), Total Cholesterol (TC), High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C) | HDL-C | -0.24 mmol/L |
| Placebo | Change From Baseline to Week 12 in Triglycerides (TG), Total Cholesterol (TC), High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C) | TG | 0.05 mmol/L |
Comparison: Analysis for TG.p-value: 0.17695% CI: [-0.43, 0.08]ANCOVA
Comparison: Analysis for TG.p-value: 0.78395% CI: [-0.3, 0.23]ANCOVA
Comparison: Analysis for TC.p-value: 0.06195% CI: [-1.31, 0.03]ANCOVA
Comparison: Analysis for TC.p-value: 0.0895% CI: [-1.34, 0.08]ANCOVA
Comparison: Analysis for HDL-C.p-value: 0.58495% CI: [-0.21, 0.37]ANCOVA
Comparison: Analysis for HDL-C.p-value: 0.14895% CI: [-0.51, 0.08]ANCOVA
Comparison: Analysis for LDL-C.p-value: 0.07495% CI: [-1.04, 0.05]ANCOVA
Comparison: Analysis for LDL-C.p-value: 0.30495% CI: [-0.87, 0.28]ANCOVA
Secondary
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.
Time frame: Baseline to Week 12
Population: Results are presented for participants from the Full Efficacy Population that have data available for analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| EDP-305 1 mg | Change From Baseline to Week 12 in Visual Analog Score (VAS) for Itching | 0.55 Scores on a scale |
| EDP-305 2.5 mg | Change From Baseline to Week 12 in Visual Analog Score (VAS) for Itching | 13.64 Scores on a scale |
| Placebo | Change From Baseline to Week 12 in Visual Analog Score (VAS) for Itching | -11.93 Scores on a scale |
p-value: 0.1695% CI: [-5.09, 30.06]ANCOVA
p-value: 0.00695% CI: [7.67, 43.48]ANCOVA
Secondary
Maximum Plasma Concentration (Cmax) of EDP-305 and Its Metabolites
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
Population: Blood samples for Pharmacokinetic (PK) analysis were collected from a subset of study sites and included participants who received active study drug and had any measurable plasma concentration of study drug at any timepoint. Results are presented for participants that have data available for analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| EDP-305 1 mg | Maximum Plasma Concentration (Cmax) of EDP-305 and Its Metabolites | EDP-305 Day 1 | 15.4 ng/mL | Geometric Coefficient of Variation 44.3 |
| EDP-305 1 mg | Maximum Plasma Concentration (Cmax) of EDP-305 and Its Metabolites | EDP-305 Week 12 | 10.8 ng/mL | Geometric Coefficient of Variation 67.77 |
| EDP-305 1 mg | Maximum Plasma Concentration (Cmax) of EDP-305 and Its Metabolites | EP-022571 Day 1 | 0.5 ng/mL | Geometric Coefficient of Variation 44.58 |
| EDP-305 1 mg | Maximum Plasma Concentration (Cmax) of EDP-305 and Its Metabolites | EP-022571 Week 12 | 0.2 ng/mL | Geometric Coefficient of Variation 59.57 |
| EDP-305 1 mg | Maximum Plasma Concentration (Cmax) of EDP-305 and Its Metabolites | EP-022572 Day 1 | 0.5 ng/mL | Geometric Coefficient of Variation 41.69 |
| EDP-305 1 mg | Maximum Plasma Concentration (Cmax) of EDP-305 and Its Metabolites | EP-022572 Week 12 | 0.2 ng/mL | Geometric Coefficient of Variation 41.74 |
| EDP-305 1 mg | Maximum Plasma Concentration (Cmax) of EDP-305 and Its Metabolites | EP-022679 Day 1 | 0.8 ng/mL | Geometric Coefficient of Variation 113.24 |
| EDP-305 1 mg | Maximum Plasma Concentration (Cmax) of EDP-305 and Its Metabolites | EP-022679 Week 12 | 0.6 ng/mL | Geometric Coefficient of Variation 147.81 |
| EDP-305 2.5 mg | Maximum Plasma Concentration (Cmax) of EDP-305 and Its Metabolites | EP-022679 Week 12 | 10.9 ng/mL | Geometric Coefficient of Variation 352.53 |
| EDP-305 2.5 mg | Maximum Plasma Concentration (Cmax) of EDP-305 and Its Metabolites | EDP-305 Day 1 | 27.9 ng/mL | Geometric Coefficient of Variation 54.19 |
| EDP-305 2.5 mg | Maximum Plasma Concentration (Cmax) of EDP-305 and Its Metabolites | EP-022572 Day 1 | 0.8 ng/mL | Geometric Coefficient of Variation 38.27 |
| EDP-305 2.5 mg | Maximum Plasma Concentration (Cmax) of EDP-305 and Its Metabolites | EDP-305 Week 12 | 50.4 ng/mL | Geometric Coefficient of Variation 53.2 |
| EDP-305 2.5 mg | Maximum Plasma Concentration (Cmax) of EDP-305 and Its Metabolites | EP-022679 Day 1 | 1.7 ng/mL | Geometric Coefficient of Variation 115.17 |
| EDP-305 2.5 mg | Maximum Plasma Concentration (Cmax) of EDP-305 and Its Metabolites | EP-022571 Day 1 | 0.6 ng/mL | Geometric Coefficient of Variation 61.81 |
| EDP-305 2.5 mg | Maximum Plasma Concentration (Cmax) of EDP-305 and Its Metabolites | EP-022572 Week 12 | 1.6 ng/mL | Geometric Coefficient of Variation 138.55 |
| EDP-305 2.5 mg | Maximum Plasma Concentration (Cmax) of EDP-305 and Its Metabolites | EP-022571 Week 12 | 1.3 ng/mL | Geometric Coefficient of Variation 160.28 |
Secondary
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.
Time frame: Day 1 and Week 12: Pre-dose and 2, 6 and 8 hours post-dose
Population: Results are presented for participants from the Full Efficacy Population that have data available for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EDP-305 1 mg | 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) | BA AUC0-8 | -20.7 Percentage change from baseline | Standard Deviation 74.8 |
| EDP-305 1 mg | 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) | BA AUC2-8 | -33.6 Percentage change from baseline | Standard Deviation 76.26 |
| EDP-305 1 mg | 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) | C4 AUC2-8 | -9.2 Percentage change from baseline | Standard Deviation 66.3 |
| EDP-305 1 mg | 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) | C4 AUC0-8 | 3.7 Percentage change from baseline | Standard Deviation 51.74 |
| EDP-305 1 mg | 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) | FGF19 AUC0-8 | 24.9 Percentage change from baseline | Standard Deviation 68.9 |
| EDP-305 1 mg | 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) | FGF19 AUC 2-8 | 7.8 Percentage change from baseline | Standard Deviation 86.25 |
| EDP-305 2.5 mg | 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) | FGF19 AUC0-8 | 25.0 Percentage change from baseline | Standard Deviation 71.72 |
| EDP-305 2.5 mg | 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) | BA AUC0-8 | -51.5 Percentage change from baseline | Standard Deviation 41.06 |
| EDP-305 2.5 mg | 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) | FGF19 AUC 2-8 | 18.9 Percentage change from baseline | Standard Deviation 66.35 |
| EDP-305 2.5 mg | 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) | C4 AUC2-8 | -100.0 Percentage change from baseline | — |
| EDP-305 2.5 mg | 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) | BA AUC2-8 | -42.8 Percentage change from baseline | Standard Deviation 56.77 |
| EDP-305 2.5 mg | 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) | C4 AUC0-8 | 100.0 Percentage change from baseline | — |
| Placebo | 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) | BA AUC2-8 | -24.4 Percentage change from baseline | — |
| Placebo | 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) | FGF19 AUC0-8 | -25.9 Percentage change from baseline | — |
| Placebo | 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) | FGF19 AUC 2-8 | -25.3 Percentage change from baseline | — |
| Placebo | 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) | C4 AUC0-8 | 138.2 Percentage change from baseline | — |
| Placebo | 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) | C4 AUC2-8 | 122.5 Percentage change from baseline | — |
| Placebo | 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) | BA AUC0-8 | -26.1 Percentage change from baseline | — |
Comparison: Analysis for FGF19 AUC0-8.p-value: 0.61195% CI: [-205.97, 295.06]ANCOVA
Comparison: Analysis for FGF19 AUC0-8.p-value: 0.81995% CI: [-411.28, 351.31]ANCOVA
Comparison: Analysis for FGF19 AUC2-8.p-value: 0.81895% CI: [-251.92, 300.74]ANCOVA
Comparison: Analysis for FGF19 AUC2-8.p-value: 0.94895% CI: [-435.33, 414.27]ANCOVA
Comparison: Analysis for C4 AUC0-8.p-value: 0.41295% CI: [-475.92, 292.51]ANCOVA
Comparison: Analysis for C4 AUC0-8.p-value: 0.09495% CI: [-605.33, 104.98]ANCOVA
Comparison: Analysis for C4 AUC2-8.p-value: 0.26695% CI: [-279.15, 111.75]ANCOVA
Comparison: Analysis for C4 AUC2-8.p-value: 0.04795% CI: [-470.22, -6.15]ANCOVA
Comparison: Analysis for BA AUC0-8.p-value: 0.69495% CI: [-180.2, 237.02]ANCOVA
Comparison: Analysis for BA AUC0-8.p-value: 0.61595% CI: [-264.32, 185.32]ANCOVA
Comparison: Analysis for BA AUC2-8.p-value: 0.97495% CI: [-229.6, 235.46]ANCOVA
Comparison: Analysis for BA AUC2-8.p-value: 0.79395% CI: [-283.24, 231.15]ANCOVA
Secondary
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.
Time frame: Baseline and Week 12
Population: Results are presented for participants from the Full Efficacy Population that have data available for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EDP-305 1 mg | 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 | C4 | -18.066 Percentage change from baseline | Standard Deviation 114.9959 |
| EDP-305 1 mg | 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 | 28.10 Percentage change from baseline | Standard Deviation 94.526 |
| EDP-305 1 mg | 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 | BA | -21.79 Percentage change from baseline | Standard Deviation 74.581 |
| EDP-305 2.5 mg | 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 | C4 | -61.960 Percentage change from baseline | Standard Deviation 42.8603 |
| EDP-305 2.5 mg | 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 | 46.90 Percentage change from baseline | Standard Deviation 76.667 |
| EDP-305 2.5 mg | 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 | BA | -15.79 Percentage change from baseline | Standard Deviation 112.934 |
| Placebo | 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 | 39.83 Percentage change from baseline | Standard Deviation 100.579 |
| Placebo | 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 | BA | 3.17 Percentage change from baseline | Standard Deviation 48.656 |
| Placebo | 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 | C4 | 39.839 Percentage change from baseline | Standard Deviation 163.6265 |
Comparison: Analysis for FGF19.p-value: 0.97195% CI: [-71.51, 74.18]ANCOVA
Comparison: Analysis for FGF19.p-value: 0.88295% CI: [-68.86, 79.95]ANCOVA
Comparison: Analysis for C4.p-value: 0.24295% CI: [-139.27, 35.96]ANCOVA
Comparison: Analysis for C4.p-value: 0.04295% CI: [-184.85, -3.75]ANCOVA
Comparison: Analysis for BA.p-value: 0.5295% CI: [-101.03, 51.89]ANCOVA
Comparison: Analysis for BA.p-value: 0.67295% CI: [-103.07, 67.16]ANCOVA
Secondary
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.
Time frame: Up to approximately Week 12
Population: Full Efficacy Population: All subjects who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EDP-305 1 mg | Percentage of Participants Who Stopped Study Treatment Due to a Treatment-Emergent Adverse Event (TEAE) During On-Treatment Period | 3.2 Percentage of participants |
| EDP-305 2.5 mg | Percentage of Participants Who Stopped Study Treatment Due to a Treatment-Emergent Adverse Event (TEAE) During On-Treatment Period | 17.9 Percentage of participants |
| Placebo | Percentage of Participants Who Stopped Study Treatment Due to a Treatment-Emergent Adverse Event (TEAE) During On-Treatment Period | 0 Percentage of participants |
Secondary
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.
Time frame: Up to approximately Week 12
Population: Full Efficacy Population: All subjects who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EDP-305 1 mg | Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE) During On-Treatment Period | 71.0 Percentage of participants |
| EDP-305 2.5 mg | Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE) During On-Treatment Period | 89.3 Percentage of participants |
| Placebo | Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE) During On-Treatment Period | 88.9 Percentage of participants |
Secondary
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.
Time frame: Up to approximately Week 12
Population: Full Efficacy Population: All subjects who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EDP-305 1 mg | Percentage of Participants With a Treatment-Emergent Serious Adverse Event (SAE) During On-Treatment Period | 3.2 Percentage of participants |
| EDP-305 2.5 mg | Percentage of Participants With a Treatment-Emergent Serious Adverse Event (SAE) During On-Treatment Period | 7.1 Percentage of participants |
| Placebo | Percentage of Participants With a Treatment-Emergent Serious Adverse Event (SAE) During On-Treatment Period | 0 Percentage of participants |
Secondary
Time to Maximum Plasma Concentration (Tmax) of EDP-305 and Its Metabolites
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
Population: Blood samples for Pharmacokinetic (PK) analysis were collected from a subset of study sites and included participants who received active study drug and had any measurable plasma concentration of study drug at any timepoint. Results are presented for participants that have data available for analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| EDP-305 1 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-305 and Its Metabolites | EDP-305 Day 1 | 6.00 hours |
| EDP-305 1 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-305 and Its Metabolites | EDP-305 Week 12 | 7.01 hours |
| EDP-305 1 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-305 and Its Metabolites | EP-022571 Day 1 | 2.00 hours |
| EDP-305 1 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-305 and Its Metabolites | EP-022571 Week 12 | 6.00 hours |
| EDP-305 1 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-305 and Its Metabolites | EP-022572 Day 1 | 2.00 hours |
| EDP-305 1 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-305 and Its Metabolites | EP-022572 Week 12 | 6.00 hours |
| EDP-305 1 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-305 and Its Metabolites | EP-022679 Day 1 | 6.00 hours |
| EDP-305 1 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-305 and Its Metabolites | EP-022679 Week 12 | 6.00 hours |
| EDP-305 2.5 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-305 and Its Metabolites | EP-022679 Week 12 | 6.00 hours |
| EDP-305 2.5 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-305 and Its Metabolites | EDP-305 Day 1 | 6.02 hours |
| EDP-305 2.5 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-305 and Its Metabolites | EP-022572 Day 1 | 6.00 hours |
| EDP-305 2.5 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-305 and Its Metabolites | EDP-305 Week 12 | 6.01 hours |
| EDP-305 2.5 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-305 and Its Metabolites | EP-022679 Day 1 | 6.10 hours |
| EDP-305 2.5 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-305 and Its Metabolites | EP-022571 Day 1 | 6.00 hours |
| EDP-305 2.5 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-305 and Its Metabolites | EP-022572 Week 12 | 4.00 hours |
| EDP-305 2.5 mg | Time to Maximum Plasma Concentration (Tmax) of EDP-305 and Its Metabolites | EP-022571 Week 12 | 4.00 hours |