Seladelpar in Subjects With Primary Biliary Cholangitis (PBC)

Study Overview
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Brief Summary
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An Open Label Long-Term Study to Evaluate the Safety and Tolerability of Seladelpar in Subjects with Primary Biliary Cholangitis (PBC)

Detailed Description
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Primary: To evaluate the long-term safety and tolerability of seladelpar Secondary: To evaluate the long-term efficacy of seladelpar To evaluate the effect of seladelpar on patient-reported outcomes (pruritus)

Official Title
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ASSURE: An Open Label Long-Term Study to Evaluate the Safety and Tolerability of Seladelpar in Subjects With Primary Biliary Cholangitis (PBC)

Conditions
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Primary Biliary Cirrhosis

Intervention / Treatment
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* Drug: Seladelpar 5 mg Capsule
* Drug: Seladelpar 10 mg Capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have given written informed consent (signed and dated) Participated in a PBC study with seladelpar Females of reproductive potential must use at least one barrier contraceptive and a second effective birth control method during the study and for at least 90 days after the last dose. Male subjects who are sexually active with female partners of reproductive potential must use barrier contraception and their female partners must use a second effective birth control method during the study and for at least 90 days after the last dose Exclusion Criteria: Exclusion criteria are only applicable for subjects with a seladelpar interruption greater than 4 weeks prior to Day 1 of this study and for subjects who participated in CB8025-21838 irrespective of seladelpar interruption. Treatment-related adverse event (AE) leading to seladelpar discontinuation in a previous PBC study with seladelpar (MBX-8025) 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) AST or ALT above 3 × the upper limit of normal (ULN) Total bilirubin above 2 × ULN MELD score ≥ 12. For subjects on anticoagulation medication, evaluation of the baseline INR, in concert with any current dose adjustments in anti-coagulant medications, will be taken into account when calculating this score. This will be done in consultation with the medical monitor. Evidence of advanced PBC as defined by the Rotterdam criteria: albumin below 1× the lower limit of normal (LLN) AND total bilirubin above 1 × ULN) eGFR ≤45 mL/min/1.73 m2 (calculated by MDRD formula) Auto-immune hepatitis Primary sclerosing cholangitis Known history of alpha-1-antitrypsin deficiency Known history of chronic viral hepatitis For females, pregnancy or breast-feeding Use of colchicine, methotrexate, azathioprine, or long-term use of systemic steroids (e.g. prednisone, prednisolone, budesonide) (>2 weeks) within 2 months prior to Screening Current use of fibrates or use of fibrates within 3 months prior to Screening Current use of obeticholic acid or use of obeticholic acid within 3 months prior to Screening Use of an experimental or unapproved treatment for PBC within 3 months prior to Screening History of malignancy diagnosed or treated, actively or within 2 years, or active evaluation for malignancy; localized treatment of squamous or non-invasive basal cell skin cancers and cervical carcinoma in-situ is allowed if appropriately treated prior to Screening Treatment with any other investigational therapy or medical device within 30 days or within 5 half-lives, whatever is longer, prior to Screening 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 Immunosuppressant therapies (e.g., cyclosporine, tacrolimus, anti-TNF or other immunosuppressive biologics) Other medications that effect liver or GI functions such as absorption of medications or the roux-en-y gastric bypass procedure may be prohibited and should be discussed with the medical monitor on a case-by-case basis Positive for: Hepatitis B, defined as the presence of hepatitis B surface antigen Hepatitis C, defined as the presence of hepatitis C virus ribonucleic acid (RNA) Human immunodeficiency virus (HIV) antibody Active COVID-19 infection during screening

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Seladelpar 5 mg Capsules<br> | Drug: Seladelpar 5 mg Capsule<br>* Subjects will be assigned to a treatment group if tolerability issues noted in the previous study.<br>* Other names: MBX-8025;|
| Experimental: Seladelpar 10 mg Capsule<br> | Drug: Seladelpar 10 mg Capsule<br>* Subjects will be assigned to a treatment group unless there are tolerability issues.<br>* Other names: MBX-8025;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment emergent adverse events (TEAEs) (National Cancer Institute {NCI} Common Terminology Criteria for Adverse Events {CTCAE} Version 5.0), biochemistry and hematology results |  | Through study completion, up to 60 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death | Occurrence of overall death | 60 Months | 
| Liver transplantation | Occurrence of overall liver transplantation | 60 Months | 
| Change in MELD | MELD score ≥ 15 for at least 2 consecutive visits | 60 Months | 
| Ascites | Occurrence of overall ascites requiring treatment | 60 Months | 
| Hospitalization for variceal bleeding | Hospitalization for new onset, or recurrence, of variceal bleeding | 60 Months | 
| Hospitalization for hepatic encephalopathy | Hospitalization for new onset, or recurrence, hepatic encephalopathy (as defined by a West Haven score ≥ 2) | 60 Months | 
| Hospitalization for spontaneous bacterial peritonitis | Hospitalization for new onset, or recurrence, spontaneous bacterial peritonitis (confirmed by culture from diagnostic paracentesis) | 60 Months | 
| Response on composite endpoint | Alkaline phosphate (ALP) | 60 Months | 
| Response on composite endpoint | Total bilirubin | 60 Months | 
| Normalization of ALP | Proportion of subjects with normalization of ALP | 60 Months | 
| Laboratory Value: Serum Alkaline Phosphatase (ALP) | Serum Alkaline Phosphatase (ALP) | Through study completion, up to 60 Months | 
| Laboratory Value: Aspartate Aminotransferase (AST) | Aspartate Aminotransferase (AST) | Through study completion, up to 60 Months | 
| Laboratory Value: Alanine Aminotransferase (ALT) | Alanine Aminotransferase (ALT) | Through study completion, up to 60 Months | 
| Laboratory Value: Gamma-glutamyl Transferase (GGT) | Gamma-glutamyl Transferase (GGT) | Through study completion, up to 60 Months | 
| Laboratory Value: Bilirubin - Total Bilirubin | Bilirubin - Total Bilirubin | Through study completion, up to 60 Months | 
| Laboratory Value: Bilirubin - Conjugated Bilirubin | Bilirubin - Conjugated Bilirubin | Through study completion, up to 60 Months | 
| Laboratory Value: Bilirubin - Unconjugated Bilirubin | Bilirubin - Unconjugated Bilirubin | Through study completion, up to 60 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PBC, Primary Biliary Cholangitis (PBC)