A Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of EDP-305 in Subjects With Primary Biliary Cholangitis

NCT03394924 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: EDP 305-201
• Study Type: interventional
• Target: 68
• Locations: 9 countries
• Sites: 83

Brief Summary

A randomized, double-blind study to assess the safety, tolerability, PK and efficacy of EDP-305 in subjects with primary biliary cholangitis

Conditions

Primary Biliary Cholangitis

Keywords

PBC; Primary Biliary Cholangitis (PBC)

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (20)

• Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE) During On-Treatment Period

  Up to approximately Week 12

• Percentage of Participants With a Treatment-Emergent Serious Adverse Event (SAE) During On-Treatment Period

  Up to approximately Week 12

• Percentage of Participants Who Stopped Study Treatment Due to a Treatment-Emergent Adverse Event (TEAE) During On-Treatment Period

  Up to approximately Week 12

• Change From Baseline to Week 12 in Total, Conjugated and Unconjugated Bilirubin

  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

Study Arms (3)

EDP-305 1 mg

EXPERIMENTAL

Subjects will take 2 tablets once a day orally for 12 weeks

Drug: EDP-305 1 mg

EDP-305 2.5 mg

EXPERIMENTAL

Subjects will take 2 tablets once a day orally for 12 weeks

Drug: EDP-305 2.5 mg

Placebo

PLACEBO COMPARATOR

Subjects will take two tablets once a day orally for 12 weeks

Drug: Placebo

Interventions

EDP-305 1 mg DRUG

Two tablets daily for 12 weeks

EDP-305 1 mg

EDP-305 2.5 mg DRUG

Two tablets daily for 12 weeks

EDP-305 2.5 mg

Placebo DRUG

Two tablets daily for 12 weeks

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Enanta Pharmaceuticals, Inc: lead
• Pharmaceutical Research Associates: collaborator
• Triangle Biostatistics, LLC: collaborator

Study Sites (86)

Digestive Health Specialists of the Southeast

Dothan, Alabama, 36305, United States

Location

Arkansas Diagnostic Center

Little Rock, Arkansas, 72205, United States

Location

Texas Clinical Research Institute

Little Rock, Arkansas, 76012, United States

Location

Southern California Research Center

Coronado, California, 92118, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

California Liver Research Institue

Pasadena, California, 91105, United States

Location

Pasadena Liver Center

Pasadena, California, 91105, United States

Location

Inland Empire Liver Foundation

Rialto, California, 92377, United States

Location

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

South Denver Gastroenterology - Swedish Medical Center Office

Englewood, Colorado, 80113, United States

Location

Yale School of Medicine

New Haven, Connecticut, 06520, United States

Location

Gastroenterology Consultants of Clearwater

Clearwater, Florida, 33756-3839, United States

Location

Nature Coast Clinical Research

Inverness, Florida, 34452, United States

Location

University of Miami Leonard M. Miller School of Medicine

Miami, Florida, 33136, United States

Location

Consultative Gastroenterology

Atlanta, Georgia, 30312, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Louisiana Research Center

Shreveport, Louisiana, 71105, United States

Location

Mercy Medical Center-McAuley Plaza

Baltimore, Maryland, 21202, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Digestive Disease Associates

Catonsville, Maryland, 21228, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48377, United States

Location

CHI Health

Omaha, Nebraska, 68124, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Northwell Health

Manhasset, New York, 11030, United States

Location

Concorde Medical Group

New York, New York, 10016, United States

Location

Mount Sinai Beth Isreal

New York, New York, 10016, United States

Location

Weill Cornell Medical College

New York, New York, 10024, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Montefiore Medical Center - Bronx

The Bronx, New York, 10461-1925, United States

Location

University of Pittsburgh Medical Center - Center for Liver Disease

Pittsburgh, Pennsylvania, 15213, United States

Location

The Liver Institute at Methodist Dallas Medical Center

Dallas, Texas, 75203, United States

Location

Liver Consultants of Texas

Dallas, Texas, 76104, United States

Location

Baylor Saint Luke's Medical Center

Houston, Texas, 77030, United States

Location

American Research Corporation at the Texas Liver Institute

San Antonio, Texas, 78215, United States

Location

Liver Institute of Virginia-Bremo

Richmond, Virginia, 23602, United States

Location

Swedish First Hill Campus

Seattle, Washington, 98104, United States

Location

University of Washington

Seattle, Washington, 98195-6460, United States

Location

Nepean Hospital

Kingswood, New South Wales, 2747, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Linear Clinical Research

Perth, Western Australia, 6000, Australia

Location

Klinikum Klagenfurt Am Wörthersee

Klagenfurt, Carinthia, 9020, Austria

Location

Medizinische Universität Innsbruck

Innsbruck, Tyrol, 6020, Austria

Location

Klinikum Wels-Grieskirchen

Wels, Upper Austria, 4600, Austria

Location

CHU de Liège, Cardiology Dept.

Liège, Liege, 4000, Belgium

Location

Ziekenhuis Oost-Limburg

Genk, Limburg, 3600, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, Oost-vlaanderen, 9000, Belgium

Location

London Health Sciences Centre University Hospital

London, Ontario, N6A 5A5, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

Toronto Liver Center

Toronto, Ontario, M6H 3M1, Canada

Location

Nouvel Hôpital Civil

Strasbourg, Alsace, 67091, France

Location

Hôpital Haut-Lévêque

Pessac, Aquitaine, 33600, France

Location

Hôpital de la Croix Rousse

Lyon, Auvergne-Rhône-Alpes, 69317, France

Location

Centre Hospitalier Régional Universitaire de Lille

Lille, Hauts-de-France, 59037, France

Location

Hôpital Saint-Eloi

Montpellier, Languedoc-roussillon, 34295, France

Location

Centre Hospitalier Universitaire Amines-Picardie Hôpital Sud

Amiens, Picardie, 80054, France

Location

Hôpital Saint-Antoine

Paris, Île-de-France Region, 75012, France

Location

Hôpital Paul Brousse

Villejuif, Île-de-France Region, 94800, France

Location

Universitätsklinikum Würzburg

Würzburg, Bavaria, 97080, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt am Main, Hesse, 60590, Germany

Location

Universitätsklinikum Bonn

Bonn, North Rhine-Westphalia, 53127, Germany

Location

Universitaetsklinikum Essen

Essen, North Rhine-Westphalia, 45122, Germany

Location

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz

Mainz, Rhineland-Palatinate, 55131, Germany

Location

Universitätsklinikum Leipzig

Leipzig, Saxony, 04103, Germany

Location

Charité Universitätsmedizin Berlin

Berlin, 13353, Germany

Location

Vrije Universiteit Medisch Centrum

Amsterdam, North Holland, 1081 HV, Netherlands

Location

Leiden Universitair Medisch Centrum

Leiden, South Holland, 2333 ZA, Netherlands

Location

Universitair Medisch Centrum Utrecht

Utrecht, 3584 CX, Netherlands

Location

Hospital Universitario Donostia

Donostia / San Sebastian, Guipuzcoa, 20014, Spain

Location

Hospital Universitario Virgen de la Arrixaca

El Palmar, Murcia, 30120, Spain

Location

Hospital Universitari Vall d'Hebrón

Barcelona, 08029, Spain

Location

Hospital Universitario Ramón Y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, 39008, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, 46026, Spain

Location

Universidad de Valladolid - Hospital Universitario Rio Hortega

Valladolid, 47010, Spain

Location

University Hospitals Birmingham NHS Foundation Trust

Birmingham, England, B15 2TT, United Kingdom

Location

Cambridge University Hospitals NHS Foundation Trust

Cambridge, England, CB2 0QQ, United Kingdom

Location

The Leeds Teaching Hospitals NHS Trust

Leeds, England, LS9 7TF, United Kingdom

Location

King's College Hospital NHS Foundation Trust

London, England, SE5 9RS, United Kingdom

Location

Norfolk and Norwich University Hospitals NHS Foundation Trust

Norwich, England, NR4 7UY, United Kingdom

Location

Queen's Medical Centre - Nottingham

Nottingham, England, NG7 2UH, United Kingdom

Location

Portsmouth Hospitals NHS Trust

Portsmouth, England, PO6 3LY, United Kingdom

Location

NHS Lothian

Edinburgh, Scotland, EH16 4SA, United Kingdom

Location

MeSH Terms

Conditions

Liver Cirrhosis, Biliary

Interventions

EDP-305

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Nathalie Adda
• Organization: Enanta Pharmaceuticals, Inc.

nadda@enanta.com

+1 6176070705

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2017
• First Posted: January 9, 2018
• Study Start: December 27, 2017
• Primary Completion: December 19, 2019
• Study Completion: January 16, 2020
• Last Updated: May 18, 2021
• Results First Posted: May 18, 2021

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

AU (3); CA (3); ES (8); NL (3); GB (8); BE (3); DE (7); FR (8); US (40)