Study of OCA in Combination With BZF Evaluating Efficacy, Safety, and Tolerability in Participants With PBC

A Phase 2, Double-Blind, Randomized, Parallel Group Study Evaluating the Efficacy, Safety, and Tolerability of Obeticholic Acid Administered in Combination With Bezafibrate in Subjects With Primary Biliary Cholangitis Who Had an Inadequate Response or Who Were Unable to Tolerate Ursodeoxycholic Acid

Study to evaluate the efficacy, safety, and tolerability of investigational drug obeticholic acid (OCA) in combination with the investigational drug bezafibrate (BZF) in participants with Primary Biliary Cholangitis (PBC).

Study Overview

• Status: Active, not recruiting
• Conditions: Primary Biliary Cholangitis
• Intervention / Treatment: Drug: Bezafibrate 200 MG; Drug: OCA Placebo; Drug: Bezafibrate 400 mg Placebo; Drug: Bezafibrate 200 mg Placebo; Drug: Bezafibrate 400 MG; Drug: Obeticholic acid; Drug: OCA; Drug: Bezafibrate

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Erminia Cafasso; Email: erminia.cafasso@interceptpharma.com
• Study Contact Backup: Name: Natasha Warner; Phone Number: +44 (0)7811 381956; Email: Natasha.Warner@InterceptPharma.com

Study Locations

• Australia
  • Adelaide, Australia, 5000
    • Royal Adelaide Hospital
  • Perth
    • Bedford Park, Perth, Australia, 5042
      • Flinders Medical Centre
• Belgium
  • Leuven, Belgium, 3000
    • UZ Gasthuisberg
• Croatia
  • Zagreb, Croatia, 10000
    • Clinical Hospital Dubrava
  • Zagreb, Croatia, 10000
    • Zagreb University Hospital Center
• Czechia
  • Hradec Kralove, Czechia, 500 12
    • Hepato-Gastroenterologie HK, s.r.o.
  • Ostrava, Czechia, 722 00
    • Artroscan s.r.o., Gastroenterologicka ambulance
  • Plzen, Czechia, 301 00
    • Research Site s.r.o.
• Estonia
  • Tartu, Estonia, 51014
    • Tartu University Hospital
• France
  • Créteil, France, 940000
    • Hopital Henri Mondor
  • Grenoble, France, 38043
    • Centre Hospitalier Universitaire Grenoble
  • Lille, France, 59000
    • CHRU de Lille
  • Paris, France, 75651
    • Groupe Hospitalier Pitié Salpêtrière - Assistance publique - Hôpitaux de Paris
  • Paris, France, Paris 12
    • CHU Paris Est - Hopital Saint Antoine
• Germany
  • Hamburg, Germany, 20246
    • Universitatsklinikum Hamburg-Eppendorf UKE
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
• Greece
  • Larissa, Greece, 41110
    • Department of Medicine and Research Laboratory of Internal Medicine, University Hospital of Larissa
• Hungary
  • Budapest, Hungary, 1111
    • Budai Hepatologiai Centrum (BHC)
  • Debrecen, Hungary, 4032
    • DEOEC II. sz. Belgyógyászati Klinika
• Israel
  • Jerusalem, Israel, 91120
    • Hadassah Ein-Karem Medical Center - Liver unit
  • Tel Aviv, Israel, 6423906
    • Tel Aviv Surasky Medical Center
• Korea, Republic of
  • Busan, Korea, Republic of, 602-739
    • Pusan National University Hospital
  • Daegu, Korea, Republic of, 41944
    • Kyungpook National University Hospital
• Lithuania
  • Kaunas, Lithuania, 50161
    • Hospital of Lithuanian University of Health Sciences, Kauno Klinikos
  • Vilnius, Lithuania, 08661
    • Vlinius University
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academisch Medisch Centrum
• Norway
  • Loerenskog, Norway, 1478
    • Universitetet i Oslo - Akershus Universitetssykehus (AHUS)
• Poland
  • Warszawa, Poland, 02-781
    • Narodowy Instytut Onkologii, Klinika Gastroenterologii Onkologicznej
• Spain
  • Barcelona, Spain, 08036
    • Fundacio Clinic Per La Recerca Biomedica
  • Valencia, Spain, 46010
    • Consorcio Hospital General Universitario
• United Kingdom
  • Hull, United Kingdom, HU3 2JZ
    • Hull University Teaching Hospitals NHS Trust
  • Newcastle Upon Tyne, United Kingdom, NE2 4HH
    • Institute of Cellular Medicine, Newcastle University
  • Oxford, United Kingdom, OX3 9DU
    • John Radcliffe Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• A definite or probable diagnosis of PBC
• Qualifying ALP and/or bilirubin liver biochemistry values
• Taking Ursodeoxycholic Acid (UDCA) for at least 12 months or no UDCA for 3 months before Day 1

Exclusion Criteria:

• History or presence of other concomitant liver diseases
• Clinical complications of PBC
• History or presence of hepatic decompensating events
• Current or history of gallbladder disease
• If female, known pregnancy, or has a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating
• Treatment with commercially available OCA or other farnesoid X receptor (FXR) agonists, or participation in a previous study involving OCA within 3 months before Screening.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment A: BZF 200 milligrams (mg) Immediate release (IR); Participants will receive Bezafibrate (BZF) 200 mg IR + OCA Placebo + BZF 400 mg Placebo	Drug: Bezafibrate 200 MG; 200 mg IR tablet of Bezafibrate once daily for the remainder of the study; Drug: OCA Placebo; One tablet daily for the remainder of the study; Drug: Bezafibrate 400 mg Placebo; One tablet daily for the remainder of the study
Active Comparator: Treatment B: BZF 400 mg SR; Participants will receive BZF 400 mg SR + OCA Placebo + BZF 200 mg Placebo	Drug: OCA Placebo; One tablet daily for the remainder of the study; Drug: Bezafibrate 200 mg Placebo; One tablet daily for the remainder of the study; Drug: Bezafibrate 400 MG; 400 mg SR tablet of Bezafibrate once daily for the remainder of the study
Experimental: Treatment C: OCA 5 mg to 10 mg + BZF 200 mg IR; Participants will receive OCA 5 mg to 10 mg + BZF 200 mg IR + BZF 400 mg Placebo	Drug: Bezafibrate 200 MG; 200 mg IR tablet of Bezafibrate once daily for the remainder of the study; Drug: Bezafibrate 400 mg Placebo; One tablet daily for the remainder of the study; Drug: Obeticholic acid; 5 mg tablet of OCA once daily titrating up to a maximum of 10 mg OCA once daily
Experimental: Treatment D: OCA 5 mg to 10 mg + BZF 400 mg SR; Participants will receive OCA 5 mg to 10 mg + BZF 400 mg SR + BZF 200 mg Placebo	Drug: Bezafibrate 200 mg Placebo; One tablet daily for the remainder of the study; Drug: Bezafibrate 400 MG; 400 mg SR tablet of Bezafibrate once daily for the remainder of the study; Drug: Obeticholic acid; 5 mg tablet of OCA once daily titrating up to a maximum of 10 mg OCA once daily
Experimental: Long-term safety extension (LTSE) phase: OCA + BZF; Participants will continue the original treatment assignment allocated during the DB Period. The OCA and BZF dose may be optimized based on safety and efficacy during the DB period.	Drug: OCA; OCA one tablet will be administered.; Drug: Bezafibrate; Bezafibrate one tablet will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Alkaline Phosphatase (ALP) from baseline to Week 12 in the DB Treatment Period	Baseline, Day 1, and Weeks 4, 8, and 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Response rates of ≥10%, ≥20%, ≥30% and ≥40% reduction, and normalization of biochemical disease marker Alkaline Phosphatase (ALP)	Baseline, Day 1, and Weeks 2, 4, 6, 8, and 12
Number of participants with normalization rates of biochemical disease marker Alanine Aminotransferase (ALT), Gamma-Glutamyl Transpeptidase (GGT), Aspartate Aminotransferase (AST), total and conjugated bilirubin and lipid panel	Baseline, Day 1, and Weeks 2, 4, 6, 8, and 12
Change in GGT from baseline to Week 12	Baseline, Day 1, and Weeks 4, 8, and 12
Change in ALT from baseline to Week 12	Baseline, Day 1, and Weeks 4, 8, and 12
Change in AST from baseline to Week 12	Baseline, Day 1, and Weeks 4, 8, and 12
Change in total and conjugated bilirubin from baseline to Week 12	Baseline, Day 1, and Weeks 4, 8, and 12
Change in lipid panel from baseline to Week 12	Baseline, Day 1, and Weeks 4, 8, and 12
Change in 7 alpha (α) hydroxy 4 cholesten-3 one (C4) from baseline to Week 12	Baseline, Day 1, and Weeks 4, 8, and 12
Change in bile acid from baseline to Week 12	Baseline, Day 1, and Weeks 4,8, and 12

Collaborators and Investigators

• Sponsor: Intercept Pharmaceuticals
• Investigators: Study Director: Antonio Civitarese, M.D., Intercept Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ; American Association for Study of Liver Diseases. Primary biliary cirrhosis. Hepatology. 2009 Jul;50(1):291-308. doi: 10.1002/hep.22906. No abstract available.
• European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol. 2009 Aug;51(2):237-67. doi: 10.1016/j.jhep.2009.04.009. Epub 2009 Jun 6. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2019
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: July 14, 2020
• First Submitted That Met QC Criteria: October 14, 2020
• First Posted (Actual): October 20, 2020

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Cirrhosis; Hepatic Impairment; Liver; Primary Biliary Cholangitis; PBC; Primary Biliary Cirrhosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Biliary Tract Diseases; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Liver Cirrhosis; Cholangitis; Liver Cirrhosis, Biliary; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Bezafibrate
• Other Study ID Numbers: 747-213

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No