RESPONSE: Response to Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and an Inadequate Control to or an Intolerance to Ursodeoxycholic Acid (UDCA)

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)

To evaluate the treatment effect of seladelpar on composite biochemical improvement in cholestasis markers based on ALP and total bilirubin and to evaluate the safety of seladelpar over 12 months of treatment compared to placebo

Study Overview

• Status: Completed
• Conditions: Primary Biliary Cholangitis
• Intervention / Treatment: Drug: Seladelpar 10 mg; Drug: Placebo; Drug: Seladelpar 5 mg

• Study Type: Interventional
• Enrollment (Actual): 193
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1056ABJ
    • CINME (Centro de Investigaciones Metabolicas)
  • Caba, Argentina, C1199ABB
    • Hospital Italiano de Buenos Aires
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1426ABP
      • Centro Médico Dra. De Salvo
    • Ciudad Autonoma de Buenos Aire, Buenos Aires, Argentina, C1023AAB
      • Stat Research S.A.
    • La Plata, Buenos Aires, Argentina, B1900AX
      • Hospital Italiano de la Plata
    • Ramos Mejía, Buenos Aires, Argentina, B1704ETD
      • DIM CliniaPrivada
• Australia
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Concord Repatriation General Hospital
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane & Women's Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Alfred Hospital
    • Parkville, Victoria, Australia, 3050
      • The Royal Melbourne Hospital
• Austria
  • Wels, Austria, 4600
    • Klinikum Wels-Grieskirchen GmbH, Abteilung Fur Innere Medizin I - Gastroenterologie
• Belgium
  • Antwerpen
    • Edegem, Antwerpen, Belgium, 2650
      • UZ Antwerpen
  • Liège
    • Liege, Liège, Belgium, 4000
      • CHU de Liège
  • Oost-Vlaanderen
    • Gent, Oost-Vlaanderen, Belgium, 9000
      • AZ Maria Middelares
    • Gent, Oost-Vlaanderen, Belgium, 9000
      • Universitair Ziekenhuis Gent
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • Universitaire Ziekenhuizen Leuven
• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre
    • Toronto, Ontario, Canada, M5G 2C4
      • University Health Network
    • Vaughan, Ontario, Canada, L4L 4Y7
      • Toronto Digestive Disease Associates Inc
• Chile
  • Valparaíso, Chile, 2540364
    • Centro de Investigaciones Clinicas Vina Del Mar
  • Coquimbo
    • La Serena, Coquimbo, Chile, 1700000
      • Centro Clinico Mediterraneo
  • Los Ríos
    • Valdivia, Los Ríos, Chile, 5110683
      • Clinical Research Chile SpA
• Czechia
  • Ostrava, Czechia, 708 52
    • Fakultni nemocnice Ostrava- Interni a Kardiologicka Klinika, Oddeleni gastroenterologie, hepatologie a pankreatologie
• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg Universitetshospital, Ambulatoriet for Medicinske Mave-Tarm Sygdomme
  • Hvidovre, Denmark, 2650
    • Hvidovre Hospital
• France
  • Grenoble, France, 38043
    • CHU de Grenoble
  • Lyon, France, 69004
    • Hôpital de la Croix-Rousse
  • Paris, France, 75012
    • Hopital Saint-Antoine - Service d'Hepato-Gastro-Enterologie -184, rue du Faubourg Saint-Antoine
• Germany
  • Erlangen, Germany, 91054
    • Universitatsklinikum Erlangen, Medizinische Klinik I, Gastroenterologie
  • Frankfurt am main, Germany, 60590
    • Universitatsklinikum Frankfurt. Medizinische Klinik I
  • Hamburg, Germany, 20099
    • Ifi-Medizin GmbH
  • Herne, Germany, 44623
    • Gastroenterologische Gemeinschaftspraxis
  • Leipzig, Germany, 04103
    • Universitätsklinikum Leipzig
  • Nordrhein-Westfalen
    • Bonn, Nordrhein-Westfalen, Germany, 53127
      • Universitätsklinikum Bonn
  • Saarland
    • Homburg, Saarland, Germany, 66421
      • Universitätsklinikum des Saarlandes
• Greece
  • Larissa, Greece, 41110
    • General University Hospital of Larissa Department of Medicine and Research Laboratory of internal rv1edicine, National Expertise Center of Greece in Autoimmune liver Diseases
  • Attiki
    • Athens, Attiki, Greece, 115 27
      • Ippokrateio General Hospital of Athens
• Hungary
  • Budapest, Hungary, 1082
    • Semmelweis Egyetem
  • Kaposvár, Hungary, 7400
    • Somogy Megyei Kaposi Mór Oktató Kórház
• Israel
  • Jerusalem, Israel, 91120
    • Liver Unit
  • Ramat Gan, Israel, 52621
    • Liver Disease Center, Sheba Medical Center
  • Tel Aviv, Israel, 64239
    • Institute for Digestive Tract & Liver Disease
• Italy
  • Ancona, Italy, 60020
    • Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona-Umberto I G.M. Lancisi G. Salesi
  • Bologna, Italy, 41126
    • Nuovo Ospedale Civile S. Agostino-Estense di Baggiovara
  • Firenze, Italy, 50139
    • Azienda Ospedaliero Universitaria Careggi
  • Padova, Italy, 35128
    • Azienda Ospedaliera Università Padova
  • Palermo, Italy, 90127
    • Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
  • MB
    • Monza, MB, Italy, 20900
      • Asst Di Monza
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Pusan National University Hospital
  • Daegu, Korea, Republic of, 41944
    • Kyungpook National University Hospital
  • Gyeonggi-do, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung medical center
  • Soeul, Korea, Republic of, 03722
    • Severance Hospital Yonsei University Health System - PPDS
  • Busan Gwangyeogsi
    • Busan, Busan Gwangyeogsi, Korea, Republic of, 47392
      • Inje University Busan Paik Hospital
  • Gyeonggido
    • Bucheon-si, Gyeonggido, Korea, Republic of, 14584
      • Soon Chun Hyang University Hospital Bucheon
• Mexico
  • Ciudad de Mexico, Mexico, 06700
    • Consultorio Medico - Distrito Federal
  • Metepec, Mexico, 52140
    • Consultorio de la Doctora Maria Sarai Gonzalez Huezo
  • Mexico City, Mexico, 06100
    • Campeche No. 280, Int. 601 y 602, Col. Hipodromo, Cuauhtemoc
  • Monterrey, Mexico, 64460
    • Hospital Universitario Dr. Jose Eleuterio Gonzalez
• New Zealand
  • Canterbury
    • Christchurch, Canterbury, New Zealand, 8011
      • Gastroenterology, Christchurch Hospital
  • Otago
    • Dunedin, Otago, New Zealand, 9016
      • Gastroenterology Research Unit Dunedin Hospital
• Poland
  • Katowice, Poland, 40-752
    • Uniwersyteckie Centrum Kliniczne Im.
  • Mysłowice, Poland, 41-400
    • ID Clinic Akradiusz Pisula
• Romania
  • Bucharest, Romania, 022328
    • Fundeni Clinical Institute
• Russian Federation
  • Moscow, Russian Federation, 111123
    • State budget institution of healthcare of Moscow city "Moscow Clinical Scientific and Practical Centre n. a. A.S. Loginov" of Moscow City Healthcare, Department, Central Research Institute of Gastroenterology
  • Moscow, Russian Federation, 117198
    • Federal State Autonomous Educational Institution of Higher Education "Peoples' Friendship University of Russia", Centre of Liver Studies
  • Saint Petersburg, Russian Federation, 199034
    • Clinic of High Medical Technologies n.a. N.I. Pirogov
  • Samara, Russian Federation, 443045
    • LLC Medical Company "Hepatolog"
  • Stavropol, Russian Federation, 355017
    • Stavropol State Medical University
  • Ulyanovsk, Russian Federation, 432063
    • Ulyanovsk Regional Clinical Hospital
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic de Barcelona
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitario German Trias i Pujol
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Margues de Valdecilla
  • Malaga
    • Málaga, Malaga, Spain, 2910
      • Hospital Universitario Virgen de la Victoria
• Switzerland
  • Zürich, Switzerland, 8091
    • University of Zurich, Gastroenterology and Hepatology
• Turkey
  • Ankara, Turkey, 06800
    • Ankara Şehir Hastanesi
  • Ankara, Turkey, 06560
    • Ankara Gazi University Faculty of Medicine Hospital
  • Istanbul, Turkey, 34899
    • Marmara University Pendik Training and Research Hospital
  • Istanbul, Turkey, 34093
    • Bezmi Alem University
  • İzmir, Turkey, 35100
    • Ege University Medical Faculty
• Ukraine
  • Kharkiv, Ukraine, 61124
    • Municipal Non-profit Enterprise "City Clinical Hospital #13" of Kharkiv City Council
  • Kyiv, Ukraine, 0291
    • Medical Center OK!Clinic+LLC International Institute of Clinical Research
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • University Hospitals Birmingham NHS Foundation Trust, Heritage Building (Queen Elizabeth Hospital)
  • Hull, United Kingdom, HU3 2JZ
    • Hull Royal Infirmary
  • London, United Kingdom, SE5 9RS
    • Kings College Hospital
  • Devon
    • Plymouth, Devon, United Kingdom, PL6 8DH
      • University Hospitals Plymouth NHS Trust
  • Hampshire
    • Portsmouth, Hampshire, United Kingdom, P06 3LY
      • Portsmouth Hospitals NHS Trust
  • London, City Of
    • London, London, City Of, United Kingdom, E1 1RF
      • Barts Health NHS Trust, Royal London Hospital, Ambrose King Centre
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
      • Queen's Medical Centre
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX4 2LL
      • Gemini Clinical Trial Unit
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • The Institute for Liver Health DBA Arizona Liver Health
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Diagnostic Center
  • California
    • Palo Alto, California, United States, 94305
      • Stanford University School of Medicine
    • Pasadena, California, United States, 91105
      • California Liver Research Institute
    • Sacramento, California, United States, 95817
      • University of California, Davis Medical Center
    • San Francisco, California, United States, 94109
      • California Pacific Medical Center - Sutter Pacific Medical Foundation
  • Florida
    • Fort Myers, Florida, United States, 33912
      • Covenant Metabolic Specialists, LLC
    • Lakewood Ranch, Florida, United States, 34211
      • Florida Research Institute
    • Miami, Florida, United States, 33136
      • Schiff Center for Liver Diseases/University of Miami
    • Sarasota, Florida, United States, 34240
      • Covenant Research and Clinics, LLC
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Digestive Healthcare of Georgia
  • Illinois
    • Chicago, Illinois, United States, 60612
      • RUSH University Medical Center
    • Chicago, Illinois, United States, 60637
      • University of Chicago Hospitals
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Health Sciences Center
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Mercy Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Novi, Michigan, United States, 48377
      • Henry Ford Health System
  • Minnesota
    • Maplewood, Minnesota, United States, 55117
      • MNGI Digestive Health, P.A.
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Southern Therapy and Advanced Research, LLC (STAR)
  • Missouri
    • Saint Louis, Missouri, United States, 63104
      • Saint Louis University
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10021
      • Weill Cornell Medical College
    • New York, New York, United States, 10016
      • NYU Langone Health / NYU Grossman School of Medicine
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • North Carolina
    • Lumberton, North Carolina, United States, 28358
      • Care Access Research - Lumberton
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S Hershey Medical Center
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Center for Liver Diseases
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • Galen Hepatology
    • Germantown, Tennessee, United States, 38138
      • Gastro One
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt Digestive Disease Center
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Dallas, Texas, United States, 75203
      • The Liver Institute At Methodist Dallas Medical Center
    • Fort Hood, Texas, United States, 76104
      • Texas Digestive Disease Consultants dba GI Alliance
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • San Antonio, Texas, United States, 78215
      • American Research Corporation at the Texas Liver Institute
    • San Antonio, Texas, United States, 78229
      • Pinnacle Clinical Research, PLLC
  • Virginia
    • Richmond, Virginia, United States, 23226
      • Bon Secours Richmond Community Hospital LLC
  • Washington
    • Seattle, Washington, United States, 98105
      • Liver Institute Northwest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Must have given written informed consent (signed and dated) and any authorizations required by local law
2. 18 to 75 years old (inclusive)
3. Male or female with a definitive diagnosis of PBC
4. 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)

5. Laboratory parameters measured by the Central Laboratory at screening:

   1. ALP ≥1.67× ULN
   2. Aspartate aminotransferase (AST) ≤3× ULN
   3. ALT ≤3× ULN
   4. Total bilirubin ≤2× ULN
   5. Estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2 (calculated by the Modification of Diet in Renal Disease study equation)
   6. 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.
   7. 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.

6. 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

Exclusion Criteria:

1. Previous exposure to seladelpar (MBX-8025).
2. 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).
3. Advanced PBC as defined by the Rotterdam criteria (albumin below the lower limit of normal AND total bilirubin above 1.0× ULN)

4. Presence of clinically important hepatic decompensation, including the following:

   1. 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.
   2. 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.
   3. Cirrhosis with complications, including history or presence of spontaneous bacterial peritonitis, hepatocellular carcinoma, or hepatorenal syndrome.

5. Other chronic liver diseases:

   1. Current features of AIH as determined by the investigator based on immunoserology, liver biochemistry, or historic confirmed liver histology.
   2. PSC determined by the presence of diagnostic cholangiographic findings.
   3. History or clinical evidence of alcoholic liver disease.
   4. History or clinical evidence of alpha-1-antitrypsin deficiency.
   5. History of biopsy confirmed NASH.
   6. History or evidence of Gilbert's syndrome with elevated total bilirubin.
   7. History or evidence of hemochromatosis.
   8. Hepatitis B, defined as the presence of hepatitis B surface antigen.
   9. Hepatitis C, defined as the presence of hepatitis C virus ribonucleic acid.
   10. History, evidence, or high suspicion of hepatobiliary malignancy based on imaging, screening laboratory values, and/or clinical symptoms.
6. Known history of human immunodeficiency virus (HIV) or positive antibody test at screening
7. 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.
8. 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.
9. Treatment with obeticholic acid (OCA) or fibrates (e.g., bezafibrate, fenofibrate, elafibranor, lanifibranor, pemafibrate, saroglitizar) 6 weeks prior to screening
10. Treatment with colchicine, methotrexate, azathioprine, or long-term systemic corticosteroids (>2 weeks) during 2 months prior to screening
11. 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
12. Treatment with any other investigational therapy or device within 30 days or within 5 half-lives, whichever is longer, prior to screening
13. For females, pregnancy or breastfeeding
14. 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
15. Immunosuppressant therapies
16. 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.
17. Active COVID-19 infection during Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; One capsule daily for double-blind period, for a duration of up to 12 months
Experimental: Seladelpar 10 mg	Drug: Seladelpar 10 mg; Seladelpar 10 mg one capsule daily for double-blind period, for a duration of up to 12 months
Experimental: Seladelpar 5 mg	Drug: Seladelpar 5 mg; If down-titration needed, one capsule daily for double-blind period, for a duration of up to 12 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite endpoint of ALP and total bilirubin	ALP < 1.67× ULN,; ≥ 15% decrease in ALP, and; Total bilirubin ≤1.0× ULN	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Normalization of ALP	Proportion of subjects with ALP ≤1.0× ULN	12 months
Change in baseline numerical rating scale (NRS)	Weekly averaged pruritus NRS in subjects with baseline NRS ≥4. The NRS is a scale of 0 (no itching) to 10 (worst imaginable itching)	6 months

Collaborators and Investigators

• Sponsor: CymaBay Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2021
• Primary Completion (Actual): August 11, 2023
• Study Completion (Actual): August 11, 2023

Study Registration Dates

• First Submitted: November 4, 2020
• First Submitted That Met QC Criteria: November 4, 2020
• First Posted (Actual): November 9, 2020

Study Record Updates

• Last Update Posted (Actual): September 29, 2023
• Last Update Submitted That Met QC Criteria: September 26, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: PBC; Primary Biliary Cholangitis (PBC)
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Biliary Tract Diseases; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Liver Cirrhosis; Cholangitis; Liver Cirrhosis, Biliary; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Seladelpar
• Other Study ID Numbers: CB8025-32048

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No