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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03394924
Ethics application status
Date submitted
23/12/2017
Date registered
9/01/2018
Date last updated
23/07/2019

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 Dose 1
Treatment: Drugs - EDP-305 Dose 2
Treatment: Drugs - Placebo

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

Experimental: EDP-305 Dose 2 - 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 Dose 1
Two tablets daily for 12 weeks

Treatment: Drugs: EDP-305 Dose 2
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
Proportion of subjects with at least 20% reduction in ALP from pre-treatment value or normalization of ALP at Week 12
Timepoint [1] 0 0
Measurement at Week 12
Secondary outcome [1] 0 0
Safety as measured by • Frequency of adverse events (AEs), serious AEs, and AEs leading to discontinuation through Week 12
Timepoint [1] 0 0
Up to 12 weeks
Secondary outcome [2] 0 0
Change from baseline in Bilirubin
Timepoint [2] 0 0
Measurement at Week 12
Secondary outcome [3] 0 0
Change from Baseline in Alanine aminotransferase (ALT)
Timepoint [3] 0 0
Measurement at Week 12
Secondary outcome [4] 0 0
Change from Baseline in Aspartate aminotransferase (AST)
Timepoint [4] 0 0
Measurement at Week 12
Secondary outcome [5] 0 0
Change from Baseline in Gamma-Glutamyl transferase (GGT)
Timepoint [5] 0 0
Measurement at Week 12
Secondary outcome [6] 0 0
Change from Baseline of Enhanced Liver Fibrosis [ELF] panel
Timepoint [6] 0 0
Measurement at Week 12
Secondary outcome [7] 0 0
Change from Baseline of PRO C3
Timepoint [7] 0 0
Measurement at Week 12
Secondary outcome [8] 0 0
Change from Baseline of AST to Platelet Ratio Index [APRI]
Timepoint [8] 0 0
Measurement at Week 12
Secondary outcome [9] 0 0
Change from Baseline of fibrosis-4 [FIB-4])
Timepoint [9] 0 0
Measurement at Week 12
Secondary outcome [10] 0 0
Change from Baseline in Triglycerides (TG)
Timepoint [10] 0 0
Measurement at Week 12
Secondary outcome [11] 0 0
Change from Baseline in Total Cholesterol (TC)
Timepoint [11] 0 0
Measurement at Week 12
Secondary outcome [12] 0 0
Change from Baseline in High Density Lipoprotein Cholesterol (HDL-C)
Timepoint [12] 0 0
Measurement at Week 12
Secondary outcome [13] 0 0
Change from Baseline in Low Density Lipoprotein Cholesterol (LDL-C)
Timepoint [13] 0 0
Measurement at Week 12
Secondary outcome [14] 0 0
Change from Baseline in 5D-itch scale
Timepoint [14] 0 0
Measurement at Week 12
Secondary outcome [15] 0 0
Change from Baseline in Visual Analog Score (VAS)
Timepoint [15] 0 0
Measurement at Week 12
Secondary outcome [16] 0 0
Change from Baseline in PBC-40 Quality of Life (QoL)
Timepoint [16] 0 0
Measurement at Week 12
Secondary outcome [17] 0 0
Cmax of EDP-305
Timepoint [17] 0 0
Up to Week 12
Secondary outcome [18] 0 0
Tmax of EDP-305
Timepoint [18] 0 0
Up to Week 12
Secondary outcome [19] 0 0
AUC of EDP-305
Timepoint [19] 0 0
Up to Week 12
Secondary outcome [20] 0 0
Change from baseline of FGF19
Timepoint [20] 0 0
Up to Week 12
Secondary outcome [21] 0 0
Change from baseline of C4
Timepoint [21] 0 0
Up to Week 12
Secondary outcome [22] 0 0
Change from baseline of Total Bile Acids
Timepoint [22] 0 0
Up to Week 12

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
Gender
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
Recruiting
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
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
A randomized, double-blind study to assess the safety, tolerability, PK and efficacy of
EDP-305 in subjects with primary biliary cholangitis
Trial website
https://clinicaltrials.gov/show/NCT03394924
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
Nathalie Adda
Address 0 0
Country 0 0
Phone 0 0
617 607 0705
Fax 0 0
Email 0 0
nadda@enanta.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03394924