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 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).

Official Title
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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

Conditions
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Primary Biliary Cholangitis

Intervention / Treatment
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* Drug: Obeticholic acid
* Drug: Bezafibrate 200 MG
* Drug: OCA Placebo
* Drug: Bezafibrate 200 mg Placebo
* Drug: Bezafibrate 400 MG
* Drug: Bezafibrate 400 mg Placebo
* Drug: OCA
* Drug: Bezafibrate


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 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.

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: Treatment A: BZF 200 milligrams (mg) Immediate release (IR)<br>Participants will receive Bezafibrate (BZF) 200 mg IR + OCA Placebo + BZF 400 mg Placebo | Drug: Bezafibrate 200 MG<br>* 200 mg IR tablet of Bezafibrate once daily for the remainder of the study<br>Drug: OCA Placebo<br>* One tablet daily for the remainder of the study<br>Drug: Bezafibrate 400 mg Placebo<br>* One tablet daily for the remainder of the study<br>|
| Active Comparator: Treatment B: BZF 400 mg SR<br>Participants will receive BZF 400 mg SR + OCA Placebo + BZF 200 mg Placebo | Drug: OCA Placebo<br>* One tablet daily for the remainder of the study<br>Drug: Bezafibrate 200 mg Placebo<br>* One tablet daily for the remainder of the study<br>Drug: Bezafibrate 400 MG<br>* 400 mg SR tablet of Bezafibrate once daily for the remainder of the study<br>|
| Experimental: Treatment C: OCA 5 mg to 10 mg + BZF 200 mg IR<br>Participants will receive OCA 5 mg to 10 mg + BZF 200 mg IR + BZF 400 mg Placebo | Drug: Obeticholic acid<br>* 5 mg tablet of OCA once daily titrating up to a maximum of 10 mg OCA once daily<br>Drug: Bezafibrate 200 MG<br>* 200 mg IR tablet of Bezafibrate once daily for the remainder of the study<br>Drug: Bezafibrate 400 mg Placebo<br>* One tablet daily for the remainder of the study<br>|
| Experimental: Treatment D: OCA 5 mg to 10 mg + BZF 400 mg SR<br>Participants will receive OCA 5 mg to 10 mg + BZF 400 mg SR + BZF 200 mg Placebo | Drug: Obeticholic acid<br>* 5 mg tablet of OCA once daily titrating up to a maximum of 10 mg OCA once daily<br>Drug: Bezafibrate 200 mg Placebo<br>* One tablet daily for the remainder of the study<br>Drug: Bezafibrate 400 MG<br>* 400 mg SR tablet of Bezafibrate once daily for the remainder of the study<br>|
| Experimental: Long-term safety extension (LTSE) phase: OCA + BZF<br>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<br>* OCA one tablet will be administered.<br>Drug: Bezafibrate<br>* Bezafibrate one tablet will be administered.<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 in the DB Treatment Period |  | Baseline, Day 1, and Weeks 4, 8, and 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

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