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| Name | Class |
|---|---|
| Pharmaceutical Research Associates | OTHER |
| Triangle Biostatistics, LLC | INDUSTRY |
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A randomized, double-blind study to assess the safety, tolerability, PK and efficacy of EDP-305 in subjects with primary biliary cholangitis
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| EDP-305 1 mg | Experimental | Subjects will take 2 tablets once a day orally for 12 weeks |
|
| EDP-305 2.5 mg | Experimental | Subjects will take 2 tablets once a day orally for 12 weeks |
|
| Placebo | Placebo Comparator | Subjects will take two tablets once a day orally for 12 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| EDP-305 1 mg | Drug | Two tablets daily for 12 weeks |
| |
| EDP-305 2.5 mg |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline and Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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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:
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:
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.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Digestive Health Specialists of the Southeast | Dothan | Alabama | 36305 | United States | ||
| Arkansas Diagnostic Center |
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132 participants were screened, 64 of which were screen failures. The remaining 68 were enrolled and received trial treatment.
The trial included 68 participants from 43 sites in Australia, Canada, Europe and the United States from December 2017 to January 2020.
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| ID | Title | Description |
|---|---|---|
| FG000 | EDP-305 1 mg | Participants took EDP-305 1 milligrams (mg) as an oral tablet once daily for 12 weeks. |
| FG001 | EDP-305 2.5 mg | Participants took EDP-305 2.5 mg as an oral tablet once daily for 12 weeks. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 2, 2018 | Mar 4, 2021 |
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| Drug |
Two tablets daily for 12 weeks |
|
| Placebo | Drug | Two tablets daily for 12 weeks |
|
| Up to approximately Week 12 |
| 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. | Up to approximately Week 12 |
| 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. | Up to approximately Week 12 |
| 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. | Baseline and Week 12 |
| 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) | 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. | Baseline and Week 12 |
| 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. | Baseline and Week 12 |
| 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. | Baseline and Week 12 |
| 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 | 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. | Baseline and Week 12 |
| Change From Baseline to Week 12 in Haptoglobin and Alpha2 Macroglobulin Levels | Baseline and Week 12 |
| 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 | 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. | Baseline and Week 12 |
| 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. | Baseline to Week 12 |
| 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. | Baseline and Week 12 |
| Maximum Plasma Concentration (Cmax) of EDP-305 and Its Metabolites | Metabolites of EDP-305 are EP-022571, EP-022572, and EP-022679. | Day 1 and Week 12: Pre-dose and 2, 6 and 8 hours post-dose |
| Time to Maximum Plasma Concentration (Tmax) of EDP-305 and Its Metabolites | Metabolites of EDP-305 are EP-022571, EP-022572, and EP-022679. | Day 1 and Week 12: Pre-dose and 2, 6 and 8 hours post-dose |
| 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. | Day 1 and Week 12: Pre-dose and 2, 6 and 8 hours post-dose |
| 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. | Baseline and Week 12 |
| 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. | Day 1 and Week 12: Pre-dose and 2, 6 and 8 hours post-dose |
| Little Rock |
| Arkansas |
| 72205 |
| United States |
| Texas Clinical Research Institute | Little Rock | Arkansas | 76012 | United States |
| Southern California Research Center | Coronado | California | 92118 | United States |
| Cedars-Sinai Medical Center | Los Angeles | California | 90048 | United States |
| California Liver Research Institue | Pasadena | California | 91105 | United States |
| Pasadena Liver Center | Pasadena | California | 91105 | United States |
| Inland Empire Liver Foundation | Rialto | California | 92377 | United States |
| California Pacific Medical Center | San Francisco | California | 94115 | United States |
| South Denver Gastroenterology - Swedish Medical Center Office | Englewood | Colorado | 80113 | United States |
| Yale School of Medicine | New Haven | Connecticut | 06520 | United States |
| Gastroenterology Consultants of Clearwater | Clearwater | Florida | 33756-3839 | United States |
| Nature Coast Clinical Research | Inverness | Florida | 34452 | United States |
| University of Miami Leonard M. Miller School of Medicine | Miami | Florida | 33136 | United States |
| Consultative Gastroenterology | Atlanta | Georgia | 30312 | United States |
| Northwestern University | Chicago | Illinois | 60611 | United States |
| University of Iowa Hospitals and Clinics | Iowa City | Iowa | 52242 | United States |
| Louisiana Research Center | Shreveport | Louisiana | 71105 | United States |
| Mercy Medical Center-McAuley Plaza | Baltimore | Maryland | 21202 | United States |
| Johns Hopkins University | Baltimore | Maryland | 21287 | United States |
| Digestive Disease Associates | Catonsville | Maryland | 21228 | United States |
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| Beth Israel Deaconess Medical Center | Boston | Massachusetts | 02215 | United States |
| Henry Ford Hospital | Detroit | Michigan | 48377 | United States |
| CHI Health | Omaha | Nebraska | 68124 | United States |
| Dartmouth-Hitchcock Medical Center | Lebanon | New Hampshire | 03756 | United States |
| Northwell Health | Manhasset | New York | 11030 | United States |
| Concorde Medical Group | New York | New York | 10016 | United States |
| Mount Sinai Beth Isreal | New York | New York | 10016 | United States |
| Weill Cornell Medical College | New York | New York | 10024 | United States |
| Icahn School of Medicine at Mount Sinai | New York | New York | 10029 | United States |
| Montefiore Medical Center - Bronx | The Bronx | New York | 10461-1925 | United States |
| University of Pittsburgh Medical Center - Center for Liver Disease | Pittsburgh | Pennsylvania | 15213 | United States |
| The Liver Institute at Methodist Dallas Medical Center | Dallas | Texas | 75203 | United States |
| Liver Consultants of Texas | Dallas | Texas | 76104 | United States |
| Baylor Saint Luke's Medical Center | Houston | Texas | 77030 | United States |
| American Research Corporation at the Texas Liver Institute | San Antonio | Texas | 78215 | United States |
| Liver Institute of Virginia-Bremo | Richmond | Virginia | 23602 | United States |
| Swedish First Hill Campus | Seattle | Washington | 98104 | United States |
| University of Washington | Seattle | Washington | 98195-6460 | United States |
| Nepean Hospital | Kingswood | New South Wales | 2747 | Australia |
| Monash Medical Centre | Clayton | Victoria | 3168 | Australia |
| Linear Clinical Research | Perth | Western Australia | 6000 | Australia |
| Klinikum Klagenfurt Am Wörthersee | Klagenfurt | Carinthia | 9020 | Austria |
| Medizinische Universität Innsbruck | Innsbruck | Tyrol | 6020 | Austria |
| Klinikum Wels-Grieskirchen | Wels | Upper Austria | 4600 | Austria |
| CHU de Liège, Cardiology Dept. | Liège | Liege | 4000 | Belgium |
| Ziekenhuis Oost-Limburg | Genk | Limburg | 3600 | Belgium |
| Universitair Ziekenhuis Gent | Ghent | Oost-vlaanderen | 9000 | Belgium |
| London Health Sciences Centre University Hospital | London | Ontario | N6A 5A5 | Canada |
| Toronto General Hospital | Toronto | Ontario | M5G 2C4 | Canada |
| Toronto Liver Center | Toronto | Ontario | M6H 3M1 | Canada |
| Nouvel Hôpital Civil | Strasbourg | Alsace | 67091 | France |
| Hôpital Haut-Lévêque | Pessac | Aquitaine | 33600 | France |
| Hôpital de la Croix Rousse | Lyon | Auvergne-Rhône-Alpes | 69317 | France |
| Centre Hospitalier Régional Universitaire de Lille | Lille | Hauts-de-France | 59037 | France |
| Hôpital Saint-Eloi | Montpellier | Languedoc-roussillon | 34295 | France |
| Centre Hospitalier Universitaire Amines-Picardie Hôpital Sud | Amiens | Picardie | 80054 | France |
| Hôpital Saint-Antoine | Paris | Île-de-France Region | 75012 | France |
| Hôpital Paul Brousse | Villejuif | Île-de-France Region | 94800 | France |
| Universitätsklinikum Würzburg | Würzburg | Bavaria | 97080 | Germany |
| Universitätsklinikum Frankfurt | Frankfurt am Main | Hesse | 60590 | Germany |
| Universitätsklinikum Bonn | Bonn | North Rhine-Westphalia | 53127 | Germany |
| Universitaetsklinikum Essen | Essen | North Rhine-Westphalia | 45122 | Germany |
| Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz | Mainz | Rhineland-Palatinate | 55131 | Germany |
| Universitätsklinikum Leipzig | Leipzig | Saxony | 04103 | Germany |
| Charité Universitätsmedizin Berlin | Berlin | 13353 | Germany |
| Vrije Universiteit Medisch Centrum | Amsterdam | North Holland | 1081 HV | Netherlands |
| Leiden Universitair Medisch Centrum | Leiden | South Holland | 2333 ZA | Netherlands |
| Universitair Medisch Centrum Utrecht | Utrecht | 3584 CX | Netherlands |
| Hospital Universitario Donostia | Donostia / San Sebastian | Guipuzcoa | 20014 | Spain |
| Hospital Universitario Virgen de la Arrixaca | El Palmar | Murcia | 30120 | Spain |
| Hospital Universitari Vall d'Hebrón | Barcelona | 08029 | Spain |
| Hospital Universitario Ramón Y Cajal | Madrid | 28034 | Spain |
| Hospital Universitario Marqués de Valdecilla | Santander | 39008 | Spain |
| Hospital Universitario Virgen del Rocio | Seville | 41013 | Spain |
| Hospital Universitari i Politecnic La Fe de Valencia | Valencia | 46026 | Spain |
| Universidad de Valladolid - Hospital Universitario Rio Hortega | Valladolid | 47010 | Spain |
| University Hospitals Birmingham NHS Foundation Trust | Birmingham | England | B15 2TT | United Kingdom |
| Cambridge University Hospitals NHS Foundation Trust | Cambridge | England | CB2 0QQ | United Kingdom |
| The Leeds Teaching Hospitals NHS Trust | Leeds | England | LS9 7TF | United Kingdom |
| King's College Hospital NHS Foundation Trust | London | England | SE5 9RS | United Kingdom |
| Norfolk and Norwich University Hospitals NHS Foundation Trust | Norwich | England | NR4 7UY | United Kingdom |
| Queen's Medical Centre - Nottingham | Nottingham | England | NG7 2UH | United Kingdom |
| Portsmouth Hospitals NHS Trust | Portsmouth | England | PO6 3LY | United Kingdom |
| NHS Lothian | Edinburgh | Scotland | EH16 4SA | United Kingdom |
| FG002 | Placebo | Participants received an oral placebo matching EDP-305 once daily for 12 weeks. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | EDP-305 1 mg | Participants took EDP-305 1 mg as an oral tablet once daily for 12 weeks. |
| BG001 | EDP-305 2.5 mg | Participants took EDP-305 2.5 mg as an oral tablet once daily for 12 weeks. |
| BG002 | Placebo | Participants received an oral placebo matching EDP-305 once daily for 12 weeks. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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. | Full Efficacy Population: All subjects who received at least one dose of study drug. | Posted | Number | percentage of participants | Baseline and Week 12 |
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| 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. | Full Efficacy Population: All subjects who received at least one dose of study drug. | Posted | Number | Percentage of participants | Up to approximately Week 12 |
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| 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. | Full Efficacy Population: All subjects who received at least one dose of study drug. | Posted | Number | Percentage of participants | Up to approximately Week 12 |
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| 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. | Full Efficacy Population: All subjects who received at least one dose of study drug. | Posted | Number | Percentage of participants | Up to approximately Week 12 |
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| 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. | Results are presented for participants from the Full Efficacy Population that have data available for analysis. | Posted | Least Squares Mean | 95% Confidence Interval | μmol/L | Baseline and Week 12 |
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| Secondary | Change From Baseline to Week 12 in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) | Results are presented for participants from the Full Efficacy Population that have data available for analysis. | Posted | Least Squares Mean | 95% Confidence Interval | U/L | Baseline and Week 12 |
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| 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. | Results are presented for participants from the Full Efficacy Population that have data available for analysis. | Posted | Least Squares Mean | 95% Confidence Interval | μg/L | Baseline and Week 12 |
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| 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. | Results are presented for participants from the Full Efficacy Population that have data available for analysis. | Posted | Least Squares Mean | 95% Confidence Interval | Index | Baseline and Week 12 |
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| 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. | Results are presented for participants from the Full Efficacy Population that have data available for analysis. | Posted | Least Squares Mean | 95% Confidence Interval | Index | Baseline and Week 12 |
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| Secondary | Change From Baseline to Week 12 in Fibrinogen and C Reactive Protein (CRP) Levels | Results are presented for participants from the Full Efficacy Population that have data available for analysis. | Posted | Least Squares Mean | 95% Confidence Interval | mg/dL | Baseline and Week 12 |
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| 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. | Results are presented for participants from the Full Efficacy Population that have data available for analysis. | Posted | Least Squares Mean | 95% Confidence Interval | ng/L | Baseline and Week 12 |
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| Secondary | Change From Baseline to Week 12 in Haptoglobin and Alpha2 Macroglobulin Levels | Results are presented for participants from the Full Efficacy Population that have data available for analysis. | Posted | Least Squares Mean | 95% Confidence Interval | g/L | Baseline and Week 12 |
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| 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) | Results are presented for participants from the Full Efficacy Population that have data available for analysis. | Posted | Least Squares Mean | 95% Confidence Interval | mmol/L | Baseline and Week 12 |
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| 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. | Results are presented for participants from the Full Efficacy Population that have data available for analysis. | Posted | Least Squares Mean | 95% Confidence Interval | Scores on a scale | Baseline and Week 12 |
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| 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. | Results are presented for participants from the Full Efficacy Population that have data available for analysis. | Posted | Least Squares Mean | 95% Confidence Interval | Scores on a scale | Baseline to Week 12 |
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| 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. | Results are presented for participants from the Full Efficacy Population that have data available for analysis. | Posted | Least Squares Mean | 95% Confidence Interval | Scores on a scale | Baseline and Week 12 |
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| Secondary | Maximum Plasma Concentration (Cmax) of EDP-305 and Its Metabolites | Metabolites of EDP-305 are EP-022571, EP-022572, and EP-022679. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Day 1 and Week 12: Pre-dose and 2, 6 and 8 hours post-dose |
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| 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. | 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. | Posted | Median | Full Range | hours | Day 1 and Week 12: Pre-dose and 2, 6 and 8 hours post-dose |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Day 1 and Week 12: Pre-dose and 2, 6 and 8 hours post-dose |
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| 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. | Results are presented for participants from the Full Efficacy Population that have data available for analysis. | Posted | Mean | Standard Deviation | Percentage change from baseline | Baseline and Week 12 |
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| 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. | Results are presented for participants from the Full Efficacy Population that have data available for analysis. | Posted | Mean | Standard Deviation | Percentage change from baseline | Day 1 and Week 12: Pre-dose and 2, 6 and 8 hours post-dose |
|
Up to 16 Weeks
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | EDP-305 1 mg | Participants took EDP-305 1 mg as an oral tablet once daily for 12 weeks. | 0 | 31 | 1 | 31 | 23 | 31 |
| EG001 | EDP-305 2.5 mg | Participants took EDP-305 2.5 mg as an oral tablet once daily for 12 weeks. | 0 | 28 | 2 | 28 | 24 | 28 |
| EG002 | Placebo | Participants received an oral placebo matching EDP-305 once daily for 12 weeks. | 0 | 9 | 0 | 9 | 8 | 9 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Pruritis | Gastrointestinal disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Urticaria | Gastrointestinal disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Escherichia urinary tract infection | Infections and infestations | MedDRA (20.1) | Systematic Assessment |
| |
| Bacterial infection | Infections and infestations | MedDRA (20.1) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fall | Injury, poisoning and procedural complications | MedDRA (20.1) | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA (20.1) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Amnesia | Nervous system disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Hyperaesthesia | Nervous system disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Swelling | General disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Menorrhagia | Reproductive system and breast disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Pruritus generalised | Skin and subcutaneous tissue disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Bursitis | Musculoskeletal and connective tissue disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (20.1) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (20.1) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (20.1) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (20.1) | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA (20.1) | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (20.1) | Systematic Assessment |
| |
| Cytomegalovirus infection | Infections and infestations | MedDRA (20.1) | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Nathalie Adda | Enanta Pharmaceuticals, Inc. | +1 6176070705 | nadda@enanta.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 9, 2020 | Mar 4, 2021 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D008105 | Liver Cirrhosis, Biliary |
| ID | Term |
|---|---|
| D002780 | Cholestasis, Intrahepatic |
| D002779 | Cholestasis |
| D001649 | Bile Duct Diseases |
| D001660 | Biliary Tract Diseases |
| D004066 | Digestive System Diseases |
| D008107 | Liver Diseases |
| D008103 | Liver Cirrhosis |
| D005355 | Fibrosis |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C000709367 | EDP-305 |
Not provided
Not provided
Not provided
| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| All other races |
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| Canada |
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| Australia |
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| Spain |
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| United Kingdom |
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| Austria |
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| Belgium |
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| France |
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| Germany |
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| Netherlands |
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| Odds Ratio (OR) |
| 7 |
| 2-Sided |
| 95 |
| 0.75 |
| 65.22 |
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| OG002 | Placebo | Participants received an oral placebo matching EDP-305 once daily for 12 weeks. |
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