Study to Evaluate the Effects of Two Doses of MBX-8025 in Subjects With Primary Biliary Cirrhosis (PBC)

Study Overview
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Brief Summary
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A 12-week, double-blind, randomized, placebo-controlled, Phase 2 study, to evaluate the effects of two doses of seladelpar/MBX-8025 in subjects with Primary Biliary Cirrhosis (PBC) and an inadequate response to ursodeoxycholic acid (UDCA)

Detailed Description
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Primary: To evaluate the effect of MBX-8025 on Alkaline Phosphatase (AP) levels Secondary: To evaluate the safety and tolerability of MBX-8025 in subjects with Primary Biliary Cirrhosis (PBC) To evaluate the effects of MBX-8025 on Primary Biliary Cirrhosis (PBC) response criteria To evaluate the effects of MBX-8025 on other markers of liver function, lipids, pruritus and Quality of Life (QoL) Exploratory: To evaluate the effect of MBX-8025 on liver imaging and other biochemical markers that may be relevant to the pathophysiology of PBC or the mechanism of action of the drug

Official Title
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A 12-week, Double-blind, Randomized, Placebo-controlled, Phase 2 Study, to Evaluate the Effects of Two Doses of MBX-8025 in Subjects With Primary Biliary Cirrhosis (PBC) and an Inadequate Response to Ursodeoxycholic Acid (UDCA)

Conditions
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Primary Biliary Cirrhosis (PBC)

Intervention / Treatment
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* Drug: Placebo Comparator
* Drug: Experimental: Seladelpar / MBX-8025 50 mg
* Drug: Experimental: Seladelpar / MBX-8025 200 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have given written informed consent (signed and dated) and any authorizations required by local law 18 to 75 years old (inclusive) Male or female with a diagnosis of PBC, by at least two of the following criteria: History of AP above ULN for at least six months Positive Anti-Mitochondrial Antibodies (AMA) titers (>1/40 on immunofluorescence or M2 positive by enzyme linked immunosorbent assay (ELISA) or positive PBC-specific antinuclear antibodies Documented liver biopsy result consistent with PBC On a stable and recommended dose of UDCA for the past twelve months AP ≥ 1.67 × ULN For females of reproductive potential, use of at least one barrier contraceptive and a second effective birth control method during the study and for at least two weeks after the last dose. For male subjects, use of appropriate contraception (e.g., condoms), so their female partners of reproductive potential do not become pregnant during the study and for at least two weeks after the last dose Exclusion Criteria: A medical condition, other than PBC, that in the investigator's opinion would preclude full participation in the study or confound its results (e.g., cancer on active treatment) AST or ALT > 3 × ULN Total bilirubin > 2 × ULN Auto-immune hepatitis Primary sclerosing cholangitis Known history of alpha-1-Antitrypsin deficiency Known history of chronic viral hepatitis Creatine kinase above ULN Serum creatinine above ULN For females, pregnancy or breast-feeding Use of colchicine, methotrexate, azathioprine, or systemic steroids in the two months preceding screening Current use of fibrates, including fenofibrates, or simvastatin Use of an experimental treatment for PBC Use of experimental or unapproved immunosuppressant Any other condition(s) that would compromise the safety of the subject or compromise the quality of the clinical study, as judged by the Investigator

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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 |
| --- | --- |
| Placebo Comparator: Placebo Dose<br>Placebo Capsule Two Capsules Daily | Drug: Placebo Comparator<br>* Placebo Capsule (2 taken once daily)<br>* Other names: Placebo;|
| Experimental: Seladelpar / MBX-8025 50 mg Dose<br>MBX-8025 50 mg capsule One Capsule Daily | Drug: Experimental: Seladelpar / MBX-8025 50 mg<br>* MBX-8025 50 mg capsule (1 taken once daily)<br>* Other names: MBX-8025 50 mg dose;|
| Experimental: Seladelpar / MBX-8025 200 mg Dose<br>MBX-8025 100 mg capsules (2 taken once daily) | Drug: Experimental: Seladelpar / MBX-8025 200 mg<br>* MBX-8025 100 mg capsules (2 taken once daily)<br>* Other names: MBX-8025 100 mg capsules;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Alkaline Phosphatase (AP) |  | 12-Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite Endpoint of AP and Bilirubin | AP < 1.67 × upper limit of normal (ULN) and Total Bilirubin within normal limit and > 15% decrease in AP | 12-Weeks | 
| Laboratory Values | Aspartate aminotransferase (AST) | 12-Weeks | 
| Laboratory Values | Alanine aminotransferase (ALT) | 12-Weeks | 
| Laboratory Values | Gamma-glutamyl transferase (GGT) | 12-Weeks | 
| Laboratory Values | 5'nucleotidase | 12-Weeks | 
| Laboratory Values | Bilirubin (Total, Conjugated, Unconjugated) | 12-Weeks | 
| Laboratory Values | Bone-specific AP | 12-Weeks | 
| Laboratory Values | Triglycerides (TG) | 12-Weeks | 
| Laboratory Values | Total Cholesterol (TC) | 12-Weeks | 
| Laboratory Values | High Density Lipoprotein Cholesterol (HDL-C) | 12-Weeks | 
| Laboratory Values | Low Density Lipoprotein Cholesterol (LDL-C) | 12-Weeks | 
| Published PBC response criteria | Paris I | 12-Weeks | 
| Published PBC response criteria | Paris II | 12-Weeks | 
| Published PBC response criteria | Toronto I | 12-Weeks | 
| Published PBC response criteria | Toronto II | 12-Weeks | 
| Published PBC response criteria | United Kingdom (UK) UK-PBC risk score | 12-Weeks | 
| 5D-itch scale |  | 12-Weeks | 
| Visual Analog Score (VAS) |  | 12-Weeks | 
| PBC-40 Quality of Life (QoL) |  | 12-Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PBC