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

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Primary Biliary Cholangitis

Intervention / Treatment
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* Drug: Bezafibrate 100 mg
* Drug: Bezafibrate 200 mg
* Drug: Obeticholic Acid 5 mg
* Drug: Obeticholic Acid placebo
* Drug: Bezafibrate Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Double Blind (DB) Phase Treatment A: BZF 100 milligrams (mg) Immediate Release (IR) tablet<br>Each Participant will take one OCA placebo tablet, one BZF 100 mg IR tablet and one BZF placebo tablet daily. | Drug: Bezafibrate 100 mg<br>* One tablet of bezafibrate 100 mg IR once daily<br>Drug: Obeticholic Acid placebo<br>* One tablet of obeticholic acid placebo tablet once daily<br>Drug: Bezafibrate Placebo<br>* One tablet of bezafibrate placebo tablet once daily<br>|
| Active Comparator: Double Blind (DB) Phase Treatment B: BZF 400 mg IR tablet<br>Each Participant will take one OCA placebo tablet and two BZF 200 mg IR tablets (to achieve 400 mg dose) daily. | Drug: Bezafibrate 200 mg<br>* Two tablets of bezafibrate 200 mg IR once daily for BZF 400 mg IR<br>Drug: Obeticholic Acid placebo<br>* One tablet of obeticholic acid placebo tablet once daily<br>|
| Experimental: Double Blind (DB) Phase Treatment C: OCA 5 mg + BZF 100 mg IR<br>Each participant will take one OCA 5 mg tablet, one BZF 100 mg IR tablet and one BZF placebo tablet, daily. | Drug: Bezafibrate 100 mg<br>* One tablet of bezafibrate 100 mg IR once daily<br>Drug: Obeticholic Acid 5 mg<br>* One tablet of obeticholic acid 5 mg tablet once daily.<br>Drug: Bezafibrate Placebo<br>* One tablet of bezafibrate placebo tablet once daily<br>|
| Experimental: Double Blind (DB) Phase Treatment D: OCA 5 mg + BZF 400 mg IR<br>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<br>* Two tablets of bezafibrate 200 mg IR once daily for BZF 400 mg IR<br>Drug: Obeticholic Acid 5 mg<br>* One tablet of obeticholic acid 5 mg tablet once daily.<br>|
| Experimental: Long Term Safety Extension (LTSE) Phase Treatment D of the DB phase: OCA 5 mg + BZF 400 mg IR<br>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<br>* Two tablets of bezafibrate 200 mg IR once daily for BZF 400 mg IR<br>Drug: Obeticholic Acid 5 mg<br>* One tablet of obeticholic acid 5 mg tablet once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Alkaline Phosphatase (ALP) from Baseline to Week 12 |  | Baseline, and at Weeks 2, 4, 6, 8, 10 and 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in response rates of ≥10 percent, ≥20 percent, ≥30 percent and ≥40 percent reduction and normalization rates of biochemical disease marker ALP |  | Baseline and at Weeks 2, 4, 6, 8, 10 and 12 | 
| Number of participants with normalization rates of alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), alanine aminotransferase (AST), total and conjugated bilirubin and lipid panel |  | Baseline and at Weeks 2, 4, 6, 8, 10 and 12 | 
| Change from Baseline in biochemical disease marker GGT |  | Baseline and at Weeks 2, 4, 6, 8, 10 and 12 | 
| Change from Baseline in biochemical disease marker ALT |  | Baseline and at Weeks 2, 4, 6, 8, 10 and 12 | 
| Change from Baseline in biochemical disease marker AST |  | Baseline and at Weeks 2, 4, 6, 8, 10 and 12 | 
| Change from Baseline in biochemical disease markers, total & conjugated bilirubin |  | Baseline and at Weeks 2, 4, 6, 8, 10 and 12 | 
| Change from Baseline in lipid panel |  | Baseline and at Weeks 2, 4, 6, 8, 10 and 12 | 
| Change from Baseline of the plasma value of 7 alpha (α) hydroxy 4 cholesten-3 one (C4) |  | Baseline and at Weeks 2, 4, 6, 8, 10, and 12 | 
| Change from Baseline of the plasma value of bile acids, in unit of nanograms per milliliter (ng/ml) |  | Baseline and at Weeks 2, 4, 6, 8, 10, and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatic Impairment, Primary Biliary Cholangitis, Primary Biliary Cirrhosis, Cirrhosis, Liver