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: Terminated
• 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 (Actual): 75
• Phase: Phase 2

Contacts and Locations

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 Králové, Czechia, 500 12
    • Hepato-Gastroenterologie HK, s.r.o.
  • Ostrava, Czechia, 722 00
    • Artroscan s.r.o., Gastroenterologicka ambulance
  • Pilsen, 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
  • Hanover, 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
• 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
  • Warsaw, Poland, 02-781
    • Narodowy Instytut Onkologii, Klinika Gastroenterologii Onkologicznej
• South Korea
  • Busan, South Korea, 602-739
    • Pusan National University Hospital
  • Daegu, South Korea, 41944
    • Kyungpook National University Hospital
• 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	Measure Description	Time Frame
Change in Alkaline Phosphatase (ALP) From Baseline in the Double-Blind Treatment Period	Serum samples were collected at scheduled visits during the double-blind treatment period. Changes in ALP over time will be analyzed using a mixed model for repeated measures (MMRM) to assess treatment group effects across study visits. Baseline was defined as the mean of all available evaluations prior to the first administration of investigational product in the DB period. Change from Baseline was calculated as post Baseline value minus Baseline value.	Baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Response Rates of ≥10%, ≥20%, ≥30% and ≥40% Reduction From Baseline in ALP in the Double-Blind Treatment Period	Responders were defined as participants achieving a ≥10%, ≥20%, ≥30%, or ≥40% reduction from baseline in serum ALP at Week 12 with non-responder imputation applied. Baseline ALP was defined as the mean of all available evaluations prior to the first administration of investigational product in the DB period. The percentage of responders were summarized by treatment group for each response threshold and compared using a Cochran Mantel Haenszel test stratified by the randomization stratification factor.	Week 12
Normalization Rates of ALP at Week 12 in the Double-Blind Treatment Period	Percentage of participants achieving a response in serum ALP at Week 12 was assessed using non-responder imputation. Analyses of ALP response rates and normalization rates were performed using a Cochran-Mantel-Haenszel test stratified by the randomization stratification factor.	Week 12
Normalization Rates of Biochemical Disease Markers in the Double-Blind Treatment Period	Percentage of participants achieving a response in biochemical disease markers including Alanine Aminotransferase (ALT), Gamma-Glutamyl Transpeptidase (GGT), Aspartate Aminotransferase (AST), Total and conjugated Bilirubin and lipid panel (cholesterol, high density lipoprotein [HDL] and low-density lipoprotein [LDL]) at Week 12 has been presented. Analyses of response rates and normalization rates were performed using a Cochran-Mantel-Haenszel test stratified by the randomization stratification factor.	Week 12
Change From Baseline in GGT, ALT and AST Levels in the Double-Blind Treatment Period	Blood samples were collected at indicated timepoint and change from Baseline in GGT, ALT and AST were analyzed using the MMRM model and results were summarized in standard International System of Units (SI) by treatment group using descriptive statistics at baseline and at each on-study evaluation. Baseline was defined as the mean of all available evaluations prior to the first administration of investigational product in the DB period. Change from baseline was calculated as post baseline value minus baseline value.	Baseline and at Week 12
Change From Baseline in Total and Conjugated Bilirubin in the Double-Blind Treatment Period	Blood samples were collected at indicated timepoints and the changes in total and conjugated bilirubin were evaluated using MMRM to assess the effects of treatment groups over time. Baseline was defined as the mean of all available evaluations prior to the first administration of investigational product in the DB period. Change from baseline was calculated as post baseline value minus baseline value.	Baseline and at Week 12
Change From Baseline in Lipid Panel in the Double-Blind Treatment Period	Blood samples were collected at indicated timepoints and the changes in lipid panel including cholesterol, HDL and LDL were evaluated using MMRM to assess the effects of treatment groups over time. Baseline was defined as the mean of all available evaluations prior to the first administration of investigational product in the DB period. Change from Baseline was calculated as post Baseline value minus Baseline value.	Baseline and at Week 12
Change From Baseline in 7 Alpha (α) Hydroxy 4 Cholesten-3 One (C4) in the Double-Blind Treatment Period	Blood samples were collected at indicated timepoints for the assessment of C4. Baseline was defined as the mean of all available evaluations prior to the first administration of investigational product. Change from Baseline was calculated as change equals post baseline value minus baseline value.	Baseline and at Week 12
Change From Baseline in Bile Acid in the Double-Blind Treatment Period	Blood samples were collected for the assessment of bile acids. Baseline was defined as the mean of all available evaluations prior to the first administration of investigational product. Change from Baseline was calculated as change equals post Baseline value minus Baseline value.	Baseline and at Week 12

Collaborators and Investigators

• Sponsor: Intercept Pharmaceuticals
• Investigators: Study Director: Lynda Szczech, 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 (Actual): October 14, 2025
• Study Completion (Actual): October 14, 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): July 16, 2026
• Last Update Submitted That Met QC Criteria: June 17, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Cirrhosis; Hepatic Impairment; Liver; Primary Biliary Cholangitis; PBC; Primary Biliary Cirrhosis
• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Biliary Tract Diseases; Liver Diseases; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Liver Cirrhosis; Pathological Conditions, Signs and Symptoms; Fibrosis; Liver Cirrhosis, Biliary; Organic Chemicals; Ethers; Hydrocarbons; Hydrocarbons, Cyclic; Acids, Acyclic; Carboxylic Acids; Hydrocarbons, Aromatic; Amides; Phenols; Benzene Derivatives; Butyrates; Acids, Carbocyclic; Benzoates; Phenyl Ethers; Benzamides; Fibric Acids; Isobutyrates; Chlorobenzoates; Bezafibrate; obeticholic acid
• 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