Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and Compensated Cirrhosis

Study Overview
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Brief Summary
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To Evaluate the Effect of Seladelpar on Clinical Outcomes in Patients with Primary Biliary Cholangitis (PBC) and Compensated Cirrhosis.

Detailed Description
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To Evaluate the Effect of Seladelpar on Clinical Outcomes in Patients with Primary Biliary Cholangitis (PBC) and Compensated Cirrhosis.

Official Title
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AFFIRM: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effect of Seladelpar on Clinical Outcomes in Patients With Primary Biliary Cholangitis (PBC) and Compensated Cirrhosis

Conditions
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Primary Biliary Cholangitis

Intervention / Treatment
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* Drug: Seladelpar 10 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must meet the following criteria to be eligible for study participation: Must be 18 to 75 years old (inclusive) Must have a confirmed prior diagnosis of PBC Evidence of cirrhosis CP Score A or B Females of reproductive potential must use at least 1 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 Subjects must be able to comply with the instructions for study drug administration and be able to complete the study schedule of assessments (SOA) Exclusion Criteria: Subjects must not meet any of the following criteria to be eligible for study participation: Prior exposure to seladelpar A medical condition other than PBC that, in the Investigator's opinion, would preclude full participation in the study History of liver transplantation or actively listed for cadaveric or planned living donor transplant. Decompensated cirrhosis Evidence of portal vein thrombosis based on imaging at time of Screening by Doppler ultrasound or prior evidence by CT or MRI Hospitalization for liver-related complication within 12 weeks of Screening Laboratory parameters at Screening: ALP ≥10×ULN ALT or AST ≥5×ULN TB ≥5×ULN Platelet count ≤75×10^3/µL Albumin ≤2.8 g/dL Estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m^2 MELD score >12. For subjects on anticoagulation medication, baseline INR determination for MELD score calculation should take anticoagulant use into account, in consultation with the Medical Monitor. Serum alpha-fetoprotein (AFP) >20 ng/mL INR >1.7 CP-C cirrhosis History or presence of other concomitant liver diseases

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Seladelpar 10 mg<br> | Drug: Seladelpar 10 mg<br>* Seladelpar 10 mg one capsule daily for up to 36 months.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* One capsule daily for up to 36 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event Free Survival (EFS) | EFS as measured by the time from start of treatment to the first occurrence of any of the following clinical events: Death by any cause; Liver transplantation; MELD score ≥15; Ascites requiring treatment; Hospitalization for esophagus or stomach varices | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Time from start of treatment to death from any cause. | 36 months | 
| Liver transplant-free survival | Time from start of treatment to the first occurrence of liver-related death or liver liver transplantation. | 36 months | 
| Time to hospitalization | Time from start of treatment for esophagus or stomach varices | 36 months | 
| Time to Event Free Survival (EFS) | MELD score ≥15 Ascites requiring treatment progression to Child-Pugh-C (advanced hepatic dysfunction) | 36 months | 

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