CB8025-32048: RESPONSE: A Placebo-controlled, Randomized, Phase 3 Study to Evaluate the Efficacy and Safety of Seladelpar in Patients With Primary Biliary Cholangitis (PBC) and an Inadequate Response to or an Intolerance to Ursodeoxycholic Acid (UDCA)
The purpose of this study is to determine if an investigational drug, seladelpar, is safe and effective in treating patients with PBC compared to placebo. This will be done by looking at how the drug affects PBC, specifically looking at changes in laboratory parameters, such as alkaline phosphatase (ALP), bilirubin, gamma-glutamyl transferase (GGT), and other laboratory tests that are used to monitor the severity of PBC and its prognosis. This is an international, multicenter evaluation of seladelpar in a randomized, double-blind, placebo-controlled, parallel-group study in patients with PBC. Approximately 180 subjects will be randomized in 2:1 ratio (seladelpar:placebo) across approximately 150 sites worldwide.
• 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 definitive diagnosis of PBC
• UDCA for the past 12 months (stable dose for >3 months prior to screening) OR intolerant to UDCA (last dose of UDCA >3 months prior to screening)
• Laboratory parameters measured by the Central Laboratory at screening:
• ALP ≥1.67× ULN
• Aspartate aminotransferase (AST) ≤3× ULN
• ALT ≤3× ULN
• Total bilirubin ≤2× ULN
• Estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2 (calculated by the Modification of Diet in Renal Disease study equation)
• International normalized ratio (INR) below 1.1× ULN For subjects on anticoagulation therapy, INR must be maintained in the range required for prophylaxis for their specific disease.
• Platelet count ≥100×103/µL NOTE: PT, INR, and platelets can be performed locally at the Screening Visit, if deemed necessary by the investigator after consultation with the medical monitor, in cases where centrally read samples are deemed invalid.
• 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
• Previous exposure to seladelpar (MBX-8025).
• A medical condition other than PBC that, in the investigator's opinion, would preclude full participation in the study (e.g., cancer) or confound its results (e.g., Paget's disease, any active infection).
• Advanced PBC as defined by the Rotterdam criteria (albumin below the lower limit of normal AND total bilirubin above 1.0× ULN)
• Presence of clinically important hepatic decompensation, including the following:
• History of liver transplantation, current placement on liver transplantation list, or current Model for End-Stage Liver Disease (MELD) score ≥12. For subjects on anticoagulation medication, evaluation of the baseline INR, in concert with their current dose adjustments of their anticoagulant medication, will be taken into account when calculating the MELD score. This will be done in consultation with the medical monitor.
• Complications of portal hypertension, including known esophageal varices, history of variceal bleeds or related interventions (ege.g., transjugular intrahepatic portosystemic shunt placement), ascites, and hepatic encephalopathy.
• Cirrhosis with complications, including history or presence of spontaneous bacterial peritonitis, hepatocellular carcinoma, or hepatorenal syndrome.
• Other chronic liver diseases:
• Current features of AIH as determined by the investigator based on immunoserology, liver biochemistry, or historic confirmed liver histology.
• PSC determined by the presence of diagnostic cholangiographic findings.
• History or clinical evidence of alcoholic liver disease.
• History or clinical evidence of alpha-1-antitrypsin deficiency.
• History of biopsy confirmed NASH.
• History or evidence of Gilbert's syndrome with elevated total bilirubin.
• History or evidence of hemochromatosis.
• Hepatitis B, defined as the presence of hepatitis B surface antigen.
• Hepatitis C, defined as the presence of hepatitis C virus ribonucleic acid.
• History, evidence, or high suspicion of hepatobiliary malignancy based on imaging, screening laboratory values, and/or clinical symptoms.
• Known history of human immunodeficiency virus (HIV) or positive antibody test at screening
• Clinically important alcohol consumption, defined as more than 2 drink units per day (equivalent to 20 g) in women and 3 drink units per day (equivalent to 30 g) in men, or inability to quantify alcohol intake reliably.
• History of malignancy diagnosed or treated, actively or within 2 years, or ongoing evaluation for malignancy; localized treatment of squamous or noninvasive basal cell skin cancers and cervical carcinoma in situ is allowed if appropriately treated prior to screening.
• Treatment with obeticholic acid (OCA) or fibrates (e.g., bezafibrate, fenofibrate, elafibranor, lanifibranor, pemafibrate, saroglitizar) 6 weeks prior to screening
• Treatment with colchicine, methotrexate, azathioprine, or long-term systemic corticosteroids (>2 weeks) during 2 months prior to screening
• Treatment with anti-pruritic drugs (e.g., cholestyramine, naltrexone, rifampicin, sertraline, or any experimental approach) must be on a stable dose within 1 month prior to screening
• Treatment with any other investigational therapy or device within 30 days or within 5 half-lives, whichever is longer, prior to screening
• For females, pregnancy or breastfeeding
• 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
• 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.
• Active COVID-19 infection during Screening.
Drug: Seladelpar 10 mg, Drug: Placebo, Drug: Seladelpar 5 mg
Primary Biliary Cholangitis
Primary Biliary Cholangitis (PBC), PBC