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

A Phase 2a, Double-Blind, Randomized, Active Controlled, Parallel Group Study Evaluating the Efficacy, Safety, and Tolerability of Bezafibrate Administered in Combination With Obeticholic Acid in Subjects With Primary Biliary Cholangitis

Study to determine the effect of the investigational drug bezafibrate (BZF) alone and in combination with the investigational drug obeticholic acid (OCA) in participants with Primary Biliary Cholangitis (PBC).

Study Overview

• Status: Completed
• Conditions: Primary Biliary Cholangitis
• Intervention / Treatment: Drug: Obeticholic Acid placebo; Drug: Bezafibrate Placebo; Drug: Bezafibrate 100 mg; Drug: Bezafibrate 200 mg; Drug: Obeticholic Acid 5 mg

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

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Hospital Italiano de Buenos Aires
  • Pilar, Argentina
    • Hospital Universitario Austral
  • Rosario, Argentina
    • Hospital Provincial del Centenario
  • Buenos Aires
    • La Plata, Buenos Aires, Argentina
      • Hospital Italiano La Plata
    • Ramos Mejía, Buenos Aires, Argentina
      • DIM Clinical Privada
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 287
      • The Northern Alberta Clinical Trials and Research Centre
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2K5
      • Pacific Gastroenterology Associates
  • Quebec
    • Montreal, Quebec, Canada
      • University of Montreal
• Italy
  • Bologna, Italy
    • Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • California
    • Coronado, California, United States, 92118
      • Southern California Gastrointestinal (GI) and Liver Centers (SCLC) - Coronado
    • Mission Hills, California, United States, 91345
      • Facey Medical Group
  • Florida
    • Miami, Florida, United States, 33136
      • Schiff Center for Liver Diseases / University of Miami
    • Tampa, Florida, United States, 33606
      • Tampa General Medical Group
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Atlanta Hospital
  • Illinois
    • Maywood, Illinois, United States, 60459
      • Loyola University Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center Harvard Liver Research Center
  • New York
    • New York, New York, United States, 10016-6402
      • NYU Langone Medical Center
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • Wake Endoscopy Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Gastro One
    • Johnson City, Tennessee, United States, 37604
      • Gastrointestinal Associates of Northeast Tennessee
  • Texas
    • Dallas, Texas, United States, 75203
      • Methodist Clinical Research Institute (CRI)
    • Houston, Texas, United States, 77030-2717
      • Houston Methodist Cancer Center
    • San Antonio, Texas, United States, 78215
      • American Research Corporation at the Texas Liver Institute

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
• Presence of clinical complications of PBC
• History or presence of 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 participation in a previous study involving OCA, or other farnesoid X receptor (FXR) agonists, or peroxisome proliferator activated receptor (PPAR)-agonists within 3 months before Screening
• Unable to tolerate BZF or other fibrates, treatment with commercially available fibrates, or participation in a previous study involving fibrate 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: Double Blind (DB) Phase Treatment A: BZF 100 milligrams (mg) Immediate Release (IR) tablet; Each Participant will take one OCA placebo tablet, one BZF 100 mg IR tablet and one BZF placebo tablet daily.	Drug: Obeticholic Acid placebo; One tablet of obeticholic acid placebo tablet once daily; Drug: Bezafibrate Placebo; One tablet of bezafibrate placebo tablet once daily; Drug: Bezafibrate 100 mg; One tablet of bezafibrate 100 mg IR once daily
Active Comparator: Double Blind (DB) Phase Treatment B: BZF 400 mg IR tablet; Each Participant will take one OCA placebo tablet and two BZF 200 mg IR tablets (to achieve 400 mg dose) daily.	Drug: Obeticholic Acid placebo; One tablet of obeticholic acid placebo tablet once daily; Drug: Bezafibrate 200 mg; Two tablets of bezafibrate 200 mg IR once daily for BZF 400 mg IR
Experimental: Double Blind (DB) Phase Treatment C: OCA 5 mg + BZF 100 mg IR; Each participant will take one OCA 5 mg tablet, one BZF 100 mg IR tablet and one BZF placebo tablet, daily.	Drug: Bezafibrate Placebo; One tablet of bezafibrate placebo tablet once daily; Drug: Bezafibrate 100 mg; One tablet of bezafibrate 100 mg IR once daily; Drug: Obeticholic Acid 5 mg; One tablet of obeticholic acid 5 mg tablet once daily.
Experimental: Double Blind (DB) Phase Treatment D: OCA 5 mg + BZF 400 mg IR; Each participant will take one OCA 5 mg tablet and two BZF 200 mg IR tablets (to achieve 400 mg dose) daily.	Drug: Bezafibrate 200 mg; Two tablets of bezafibrate 200 mg IR once daily for BZF 400 mg IR; Drug: Obeticholic Acid 5 mg; One tablet of obeticholic acid 5 mg tablet once daily.
Experimental: Long Term Safety Extension (LTSE) Phase Treatment D of the DB phase: OCA 5 mg + BZF 400 mg IR; Each participant will take one OCA 5 mg tablet and two BZF 200 mg IR tablets (to achieve 400 mg dose) daily.	Drug: Bezafibrate 200 mg; Two tablets of bezafibrate 200 mg IR once daily for BZF 400 mg IR; Drug: Obeticholic Acid 5 mg; One tablet of obeticholic acid 5 mg tablet once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Alkaline Phosphatase (ALP)	Serum samples were collected at scheduled visits during the double-blind treatment period. Changes in ALP were evaluated using a mixed-effects repeated-measures model (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. 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	Responders were defined as participants achieving a ≥10%, ≥20%, ≥30%, or ≥40% reduction from baseline in serum ALP at week 12 during the DB treatment period with non-responder imputation applied. Baseline ALP was defined as the last evaluations prior to the first administration of investigational product. 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.	At Week 12
Normalization Rates of ALP at Week 12	Percentage of participants achieving a response in serum ALP at week 12 during the DB treatment period was assessed using non-responder imputation. Analyses of ALP normalization rates were performed using a Cochran-Mantel-Haenszel test stratified by the randomization stratification factor.	At Week 12
Normalization Rates of Biochemical Disease Markers	Percentage of participants achieving a response in biochemical disease markers including ALP, alanine amino transferase (ALT), aspartate amino transferase (AST), gamma-glutamyl transferase (GGT), total and conjugated bilirubin and lipid panel (cholesterol, high density lipoprotein [HDL] and low density lipoprotein [LDL]) at Week 12 during the DB treatment period has been presented. Analyses of response rates and normalization rates were performed using a Cochran-Mantel-Haenszel test stratified by the randomization stratification factor.	At Week 12
Change From Baseline in in GGT, ALT and AST Levels	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. 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	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. Change from baseline was calculated as post Baseline value minus Baseline value.	Baseline and At Week 12
Change From Baseline in Lipid Panel	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. Change from baseline was calculated as post Baseline value minus Baseline value.	Baseline and At Week 12
Change From Baseline of the Plasma Value of 7 Alpha (α) Hydroxy 4 Cholesten-3 One (C4)	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 post Baseline value minus Baseline value.	Baseline and At Week 12
Number of Participants With Clinically Significant Changes From Baseline in Bile Acids	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.	At Week 12

Collaborators and Investigators

• Sponsor: Intercept Pharmaceuticals
• Investigators: Study Director: Lynda Szczech, M.D., Intercept Pharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2022
• Primary Completion (Actual): September 1, 2025
• Study Completion (Actual): September 1, 2025

Study Registration Dates

• First Submitted: January 28, 2022
• First Submitted That Met QC Criteria: February 11, 2022
• First Posted (Actual): February 15, 2022

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; 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: 747-214

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No