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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03394924




Registration number
NCT03394924
Ethics application status
Date submitted
23/12/2017
Date registered
9/01/2018

Titles & IDs
Public title
A Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of EDP-305 in Subjects With Primary Biliary Cholangitis
Scientific title
A Phase 2 Dose Ranging, Randomized, Double Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of EDP-305 in Subjects With Primary Biliary Cholangitis (PBC) With or Without an Inadequate Response to Ursodeoxycholic Acid (UDCA)
Secondary ID [1] 0 0
EDP 305-201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Primary Biliary Cholangitis 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Infection 0 0 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - EDP-305 1 mg
Treatment: Drugs - EDP-305 2.5 mg
Treatment: Drugs - Placebo

Experimental: EDP-305 1 mg - Subjects will take 2 tablets once a day orally for 12 weeks

Experimental: EDP-305 2.5 mg - Subjects will take 2 tablets once a day orally for 12 weeks

Placebo comparator: Placebo - Subjects will take two tablets once a day orally for 12 weeks


Treatment: Drugs: EDP-305 1 mg
Two tablets daily for 12 weeks

Treatment: Drugs: EDP-305 2.5 mg
Two tablets daily for 12 weeks

Treatment: Drugs: Placebo
Two tablets daily for 12 weeks

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With At Least a 20% Reduction in Alkaline Phosphatase (ALP) or Normalization of ALP at Week 12 Compared to Baseline
Timepoint [1] 0 0
Baseline and Week 12
Secondary outcome [1] 0 0
Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE) During On-Treatment Period
Timepoint [1] 0 0
Up to approximately Week 12
Secondary outcome [2] 0 0
Percentage of Participants With a Treatment-Emergent Serious Adverse Event (SAE) During On-Treatment Period
Timepoint [2] 0 0
Up to approximately Week 12
Secondary outcome [3] 0 0
Percentage of Participants Who Stopped Study Treatment Due to a Treatment-Emergent Adverse Event (TEAE) During On-Treatment Period
Timepoint [3] 0 0
Up to approximately Week 12
Secondary outcome [4] 0 0
Change From Baseline to Week 12 in Total, Conjugated and Unconjugated Bilirubin
Timepoint [4] 0 0
Baseline and Week 12
Secondary outcome [5] 0 0
Change From Baseline to Week 12 in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT)
Timepoint [5] 0 0
Baseline and Week 12
Secondary outcome [6] 0 0
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)
Timepoint [6] 0 0
Baseline and Week 12
Secondary outcome [7] 0 0
Change From Baseline to Week 12 in Noninvasive Liver Fibrosis Markers: AST to Platelet Ratio Index (APRI) Score
Timepoint [7] 0 0
Baseline and Week 12
Secondary outcome [8] 0 0
Change From Baseline to Week 12 in Noninvasive Liver Fibrosis Markers: Fibrosis-4 (FIB-4) Score
Timepoint [8] 0 0
Baseline and Week 12
Secondary outcome [9] 0 0
Change From Baseline to Week 12 in Fibrinogen and C Reactive Protein (CRP) Levels
Timepoint [9] 0 0
Baseline and Week 12
Secondary outcome [10] 0 0
Change From Baseline to Week 12 in Interleukin (IL) and Tumor Necrosis Factor (TNF) Levels
Timepoint [10] 0 0
Baseline and Week 12
Secondary outcome [11] 0 0
Change From Baseline to Week 12 in Haptoglobin and Alpha2 Macroglobulin Levels
Timepoint [11] 0 0
Baseline and Week 12
Secondary outcome [12] 0 0
Change From Baseline to Week 12 in Triglycerides (TG), Total Cholesterol (TC), High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C)
Timepoint [12] 0 0
Baseline and Week 12
Secondary outcome [13] 0 0
Change From Baseline to Week 12 in Domain and Total Scores on the 5D-Itch Scale
Timepoint [13] 0 0
Baseline and Week 12
Secondary outcome [14] 0 0
Change From Baseline to Week 12 in Visual Analog Score (VAS) for Itching
Timepoint [14] 0 0
Baseline to Week 12
Secondary outcome [15] 0 0
Change From Baseline to Week 12 in Domain Scores on the Primary Biliary Cholangitis-40 (PBC-40) Quality of Life (QoL) Assessment
Timepoint [15] 0 0
Baseline and Week 12
Secondary outcome [16] 0 0
Maximum Plasma Concentration (Cmax) of EDP-305 and Its Metabolites
Timepoint [16] 0 0
Day 1 and Week 12: Pre-dose and 2, 6 and 8 hours post-dose
Secondary outcome [17] 0 0
Time to Maximum Plasma Concentration (Tmax) of EDP-305 and Its Metabolites
Timepoint [17] 0 0
Day 1 and Week 12: Pre-dose and 2, 6 and 8 hours post-dose
Secondary outcome [18] 0 0
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
Timepoint [18] 0 0
Day 1 and Week 12: Pre-dose and 2, 6 and 8 hours post-dose
Secondary outcome [19] 0 0
Percentage Change From Baseline to Week 12 in Fibroblast Growth Factor 19 (FGF19), 7a-OH-4-cholesten-3-one (C4) and Bile Acid (BA) Concentrations
Timepoint [19] 0 0
Baseline and Week 12
Secondary outcome [20] 0 0
Percentage Change From Baseline to Week 12 in AUC0-8 and AUC2-8 of Fibroblast Growth Factor 19 (FGF19), 7a-OH-4-cholesten-3-one (C4) and Bile Acid (BA)
Timepoint [20] 0 0
Day 1 and Week 12: Pre-dose and 2, 6 and 8 hours post-dose

Eligibility
Key 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
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Nepean Hospital - Kingswood
Recruitment hospital [2] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [3] 0 0
Linear Clinical Research - Perth
Recruitment postcode(s) [1] 0 0
2747 - Kingswood
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Iowa
Country [10] 0 0
United States of America
State/province [10] 0 0
Louisiana
Country [11] 0 0
United States of America
State/province [11] 0 0
Maryland
Country [12] 0 0
United States of America
State/province [12] 0 0
Massachusetts
Country [13] 0 0
United States of America
State/province [13] 0 0
Michigan
Country [14] 0 0
United States of America
State/province [14] 0 0
Nebraska
Country [15] 0 0
United States of America
State/province [15] 0 0
New Hampshire
Country [16] 0 0
United States of America
State/province [16] 0 0
New York
Country [17] 0 0
United States of America
State/province [17] 0 0
Pennsylvania
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
United States of America
State/province [19] 0 0
Virginia
Country [20] 0 0
United States of America
State/province [20] 0 0
Washington
Country [21] 0 0
Austria
State/province [21] 0 0
Carinthia
Country [22] 0 0
Austria
State/province [22] 0 0
Tyrol
Country [23] 0 0
Austria
State/province [23] 0 0
Upper Austria
Country [24] 0 0
Belgium
State/province [24] 0 0
Liege
Country [25] 0 0
Belgium
State/province [25] 0 0
Limburg
Country [26] 0 0
Belgium
State/province [26] 0 0
Oost-vlaanderen
Country [27] 0 0
Canada
State/province [27] 0 0
Ontario
Country [28] 0 0
France
State/province [28] 0 0
Alsace
Country [29] 0 0
France
State/province [29] 0 0
Aquitaine
Country [30] 0 0
France
State/province [30] 0 0
Ile-de-france
Country [31] 0 0
France
State/province [31] 0 0
Languedoc-roussillon
Country [32] 0 0
France
State/province [32] 0 0
NORD Pas-de-calais
Country [33] 0 0
France
State/province [33] 0 0
Picardie
Country [34] 0 0
France
State/province [34] 0 0
Rhone-alpes
Country [35] 0 0
Germany
State/province [35] 0 0
Bayern
Country [36] 0 0
Germany
State/province [36] 0 0
Hessen
Country [37] 0 0
Germany
State/province [37] 0 0
Nordrhein-westfalen
Country [38] 0 0
Germany
State/province [38] 0 0
Rheinland-pfalz
Country [39] 0 0
Germany
State/province [39] 0 0
Sachsen
Country [40] 0 0
Germany
State/province [40] 0 0
Berlin
Country [41] 0 0
Netherlands
State/province [41] 0 0
Noord-holland
Country [42] 0 0
Netherlands
State/province [42] 0 0
Zuid-holland
Country [43] 0 0
Netherlands
State/province [43] 0 0
Utrecht
Country [44] 0 0
Spain
State/province [44] 0 0
Guipuzcoa
Country [45] 0 0
Spain
State/province [45] 0 0
Murcia
Country [46] 0 0
Spain
State/province [46] 0 0
Barcelona
Country [47] 0 0
Spain
State/province [47] 0 0
Madrid
Country [48] 0 0
Spain
State/province [48] 0 0
Santander
Country [49] 0 0
Spain
State/province [49] 0 0
Sevilla
Country [50] 0 0
Spain
State/province [50] 0 0
Valencia
Country [51] 0 0
Spain
State/province [51] 0 0
Valladolid
Country [52] 0 0
United Kingdom
State/province [52] 0 0
England
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Scotland

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Enanta Pharmaceuticals, Inc
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Pharmaceutical Research Associates
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Triangle Biostatistics
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.