RESPONSE: Response to Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and an Inadequate Control to or an Intolerance to Ursodeoxycholic Acid (UDCA)
- Conditions
- Primary Biliary Cholangitis
- Interventions
- Registration Number
- NCT04620733
- Lead Sponsor
- CymaBay Therapeutics, Inc.
- Brief Summary
The purposes of this study are 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.
The study also checked the effect of treatment on the symptoms of PBC, including pruritus.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 193
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Must have given written informed consent (signed and dated) and any authorizations required by local law.
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Male or female with a definitive diagnosis of primary biliary cholangitis (PBC).
-
Ursodeoxycholic acid (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:
- Alkaline phosphatase (ALP) ≥1.67× ULN (upper limit of normal)
- Aspartate aminotransferase (AST) ≤3× ULN
- Alanine aminotransferase (ALT) ≤3× ULN
- Total bilirubin ≤2× ULN
- Estimated glomerular filtration rate (eGFR) >45 mL/min/1.73 m^2 (calculated by the Modification of Diet in Renal Disease study equation).
- International normalized ratio (INR) below 1.1× ULN (For individuals on anticoagulation therapy, INR must be maintained in the range required for prophylaxis for their specific disease).
- Platelet count ≥100 ×10^3/µL.
-
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 individuals 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.
Key
-
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).
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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 individuals 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 (e.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 autoimmune hepatitis (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 nonalcoholic steatohepatitis (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.
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Known history of human immunodeficiency virus (HIV) or positive antibody test at screening
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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.
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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.
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Treatment with obeticholic acid (OCA) or fibrates (e.g., bezafibrate, fenofibrate, elafibranor, lanifibranor, pemafibrate, saroglitizar) 6 weeks prior to screening.
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Treatment with colchicine, methotrexate, azathioprine, or long-term systemic corticosteroids (>2 weeks) during 2 months prior to screening
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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
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Treatment with any other investigational therapy or device within 30 days or within 5 half-lives, whichever is longer, prior to screening
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For females, pregnancy or breastfeeding.
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Any other condition(s) that would compromise the safety of the individual or compromise the quality of the clinical study, as judged by the investigator.
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Immunosuppressant therapies.
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Other medications that effect liver or gastrointestinal (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.
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Active Coronavirus Disease-2019 (COVID-19) infection during Screening.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Seladelpar Seladelpar 5 mg Participants will receive seladelpar 10 mg (or 5 mg down-titrated, for those participants who met specific safety monitoring criteria or had tolerability issues), orally, once daily, for a duration of up to 12 months. Seladelpar Seladelpar 10 mg Participants will receive seladelpar 10 mg (or 5 mg down-titrated, for those participants who met specific safety monitoring criteria or had tolerability issues), orally, once daily, for a duration of up to 12 months. Placebo Placebo Participants will receive placebo to match seladelpar, orally, once daily, for a duration of up to 12 months.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Response Criteria for the Composite Endpoint of ALP <1.67 × Upper Limit of Normal (ULN), ≥15% Reduction in ALP, and Total Bilirubin ≤ 1.0× ULN at Month 12 Month 12 Percentages were rounded-off.
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs First dose date up to last dose plus 30 days (up to 13.4 months) Percentages were rounded-off.
Percentage of Participants With Shift of ≥ 2 CTCAE Grades From Baseline in Treatment-emergent Laboratory Abnormalities Related to Hematology and Select Liver Biochemistry First dose date up to last dose (up to 13.4 months) Treatment-emergent graded laboratory abnormalities were defined as values that increase at least 2 toxicity grade from baseline at any time post baseline. The laboratory abnormalities were graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), where Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: potentially life-threatening laboratory abnormality.
The data is reported for shift of ≥ 2 grades from baseline in values for hematology and select liver biochemistry. Hematology includes parameters like RBCs, (erythrocytes), hemoglobin, hematocrit, platelets, WBC, WBC differentials (absolute and percentage) including basophils, neutrophils, lymphocytes, eosinophils, and monocytes, etc. Biochemistry included select liver function tests like blood bilirubin, gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase. Percentages were rounded-off.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Weekly Averaged Pruritus Numerical Rating Scale (NRS) in Participants With NRS ≥ 4 at Month 6 Baseline, Month 6 Pruritus NRS is used to rate the intensity of the itching experienced by the participants in the past 24 hours from no itching to worst possible itching by selecting a number from 0 to 10 on Itch Scale. Zero means no itching and 10 means worst imaginable itching.
Percentage of Participants With ALP ≤1.0× ULN at Month 12 Month 12 Percentages were rounded-off.
Trial Locations
- Locations (134)
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Consultorio de la Doctora Maria Sarai Gonzalez Huezo
🇲🇽Metepec, Mexico
UPMC Center for Liver Diseases
🇺🇸Pittsburgh, Pennsylvania, United States
Digestive Healthcare of Georgia
🇺🇸Atlanta, Georgia, United States
Mercy Medical Center
🇺🇸Baltimore, Maryland, United States
University of Chicago Hospitals
🇺🇸Chicago, Illinois, United States
University Health Network
🇨🇦Toronto, Ontario, Canada
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
American Research Corporation at the Texas Liver Institute
🇺🇸San Antonio, Texas, United States
Pinnacle Clinical Research, PLLC
🇺🇸San Antonio, Texas, United States
Schiff Center for Liver Diseases/University of Miami
🇺🇸Miami, Florida, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Universitätsklinikum des Saarlandes
🇩🇪Homburg, Saarland, Germany
California Pacific Medical Center - Sutter Pacific Medical Foundation
🇺🇸San Francisco, California, United States
Vanderbilt Digestive Disease Center
🇺🇸Nashville, Tennessee, United States
DIM CliniaPrivada
🇦🇷Ramos Mejía, Buenos Aires, Argentina
The Institute for Liver Health DBA Arizona Liver Health
🇺🇸Chandler, Arizona, United States
Hospital Italiano de Buenos Aires
🇦🇷Caba, Argentina
Somogy Megyei Kaposi Mor Oktato Korhaz
🇭🇺Kaposvár, Hungary
Liver Unit
🇮🇱Jerusalem, Israel
Fundeni Clinical Institute
🇷🇴Bucharest, Romania
LLC Medical Company "Hepatolog"
🇷🇺Samara, Russian Federation
University of Zurich, Gastroenterology and Hepatology
🇨🇭Zürich, Switzerland
Queen's Medical Centre
🇬🇧Nottingham, Nottinghamshire, United Kingdom
AZ Maria Middelares
🇧🇪Gent, Oost-Vlaanderen, Belgium
Stavropol state medical university
🇷🇺Stavropol, Russian Federation
University Hospitals Plymouth NHS Trust
🇬🇧Plymouth, Devon, United Kingdom
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Arkansas Diagnostic Center
🇺🇸Little Rock, Arkansas, United States
Centro Clinico Mediterraneo
🇨🇱La Serena, Coquimbo, Chile
Semmelweis Egyetem
🇭🇺Budapest, Hungary
STAT Research S.A.
🇦🇷Ciudad Autonoma de Buenos Aire, Buenos Aires, Argentina
CINME (Centro de Investigaciones Metabolicas)
🇦🇷Buenos Aires, Argentina
CHU de Liège
🇧🇪Liege, Liège, Belgium
Liver Disease Center, Sheba Medical Center
🇮🇱Ramat Gan, Israel
Uniwersyteckie Centrum Kliniczne Im.
🇵🇱Katowice, Poland
The Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
Centro Medico Dra. De Salvo
🇦🇷Caba, Buenos Aires, Argentina
Hospital Italiano de La Plata
🇦🇷La Plata, Buenos Aires, Argentina
Klinikum Wels-Grieskirchen GmbH, Abteilung Fur Innere Medizin I - Gastroenterologie
🇦🇹Wels, Austria
UZ Antwerpen
🇧🇪Edegem, Antwerpen, Belgium
Ippokrateio General Hospital of Athens
🇬🇷Athens, Attiki, Greece
Institute for Digestive Tract & Liver Disease
🇮🇱Tel Aviv, Israel
Portsmouth Hospitals NHS Trust
🇬🇧Portsmouth, Hampshire, United Kingdom
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
General University Hospital of Larissa Department of Medicine and Research Laboratory of internal rv1edicine, National Expertise Center of Greece in Autoimmune liver Diseases
🇬🇷Larissa, Greece
Stanford University School of Medicine
🇺🇸Palo Alto, California, United States
Covenant Metabolic Specialists, LLC
🇺🇸Fort Myers, Florida, United States
California Liver Research Institute
🇺🇸Pasadena, California, United States
University of California, Davis Medical Center
🇺🇸Sacramento, California, United States
Florida Research Institute
🇺🇸Lakewood Ranch, Florida, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Covenant Research and Clinics, LLC
🇺🇸Sarasota, Florida, United States
Tulane University Health Sciences Center
🇺🇸New Orleans, Louisiana, United States
MNGI Digestive Health, P.A.
🇺🇸Maplewood, Minnesota, United States
Saint Louis University
🇺🇸Saint Louis, Missouri, United States
NYU Langone Health / NYU Grossman School of Medicine
🇺🇸New York, New York, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Care Access Research - Lumberton
🇺🇸Lumberton, North Carolina, United States
Penn State Milton S Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Gastro One
🇺🇸Germantown, Tennessee, United States
The Liver Institute at Methodist Dallas Medical Center
🇺🇸Dallas, Texas, United States
Texas Digestive Disease Consultants dba GI Alliance
🇺🇸Fort Hood, Texas, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Liver Institute Northwest
🇺🇸Seattle, Washington, United States
Bon Secours Richmond Community Hospital LLC
🇺🇸Richmond, Virginia, United States
Concord Repatriation General Hospital
🇦🇺Concord, New South Wales, Australia
Royal Brisbane & Women's Hospital
🇦🇺Herston, Queensland, Australia
Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
London Health Sciences Centre
🇨🇦London, Ontario, Canada
Universitaire Ziekenhuizen Leuven
🇧🇪Leuven, Vlaams-Brabant, Belgium
Universitair Ziekenhuis Gent
🇧🇪Gent, Oost-Vlaanderen, Belgium
Toronto Digestive Disease Associates Inc
🇨🇦Vaughan, Ontario, Canada
Clinical Research Chile SpA
🇨🇱Valdivia, Los Ríos, Chile
Centro de Investigaciones Clínicas Vina del Mar
🇨🇱Valparaíso, Chile
Fakultni nemocnice Ostrava- Interni a Kardiologicka Klinika, Oddeleni gastroenterologie, hepatologie a pankreatologie
🇨🇿Ostrava, Czechia
Hvidovre Hospital
🇩🇰Hvidovre, Denmark
CHU de Grenoble
🇫🇷Grenoble, France
Aalborg Universitetshospital, Ambulatoriet for Medicinske Mave-Tarm Sygdomme
🇩🇰Aalborg, Denmark
Hopital de la Croix-Rousse
🇫🇷Lyon, France
Hopital Saint-Antoine - Service d'Hepato-Gastro-Enterologie -184, rue du Faubourg Saint-Antoine
🇫🇷Paris, France
Universitätsklinikum Bonn
🇩🇪Bonn, Nordrhein-Westfalen, Germany
Universitatsklinikum Frankfurt. Medizinische Klinik I
🇩🇪Frankfurt am main, Germany
Ifi-Medizin GmbH
🇩🇪Hamburg, Germany
Universitatsklinikum Erlangen, Medizinische Klinik I, Gastroenterologie
🇩🇪Erlangen, Germany
Gastroenterologische Gemeinschaftspraxis
🇩🇪Herne, Germany
Universitatsklinikum Leipzig
🇩🇪Leipzig, Germany
Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona-Umberto I G.M. Lancisi G. Salesi
🇮🇹Ancona, Italy
ASST di Monza
🇮🇹Monza, MB, Italy
Azienda Ospedaliero Universitaria Careggi
🇮🇹Firenze, Italy
Nuovo Ospedale Civile S. Agostino-Estense di Baggiovara
🇮🇹Bologna, Italy
Azienda Ospedaliera Universita Padova
🇮🇹Padova, Italy
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
🇮🇹Palermo, Italy
Soon Chun Hyang University Hospital Bucheon
🇰🇷Bucheon-si, Gyeonggido, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Inje University Busan Paik Hospital
🇰🇷Busan, Busan Gwangyeogsi, Korea, Republic of
Kyungpook National University Hospital
🇰🇷Daegu, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Consultorio Medico - Distrito Federal
🇲🇽Ciudad de Mexico, Mexico
Severance Hospital Yonsei University Health System - PPDS
🇰🇷Soeul, Korea, Republic of
Campeche No. 280, Int. 601 y 602, Col. Hipodromo, Cuauhtemoc
🇲🇽Mexico City, Mexico
Hospital Universitario Dr. Jose Eleuterio González
🇲🇽Monterrey, Mexico
Gastroenterology, Christchurch Hospital
🇳🇿Christchurch, Canterbury, New Zealand
Gastroenterology Research Unit Dunedin Hospital
🇳🇿Dunedin, Otago, New Zealand
ID Clinic Akradiusz Pisula
🇵🇱Mysłowice, Poland
Clinic of High Medical Technologies n.a. N.I. Pirogov
🇷🇺Saint Petersburg, Russian Federation
Federal State Autonomous Educational Institution of Higher Education "Peoples' Friendship University of Russia", Centre of Liver Studies
🇷🇺Moscow, Russian Federation
Hospital Universitario German Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Ulyanovsk Regional Clinical Hospital
🇷🇺Ulyanovsk, Russian Federation
Hospital Universitario Margues de Valdecilla
🇪🇸Santander, Cantabria, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario Virgen de la Victoria
🇪🇸Málaga, Malaga, Spain
Hospital Universitario Vall D'Hebron
🇪🇸Barcelona, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Ankara Gazi University Faculty of Medicine Hospital
🇹🇷Ankara, Turkey
Ankara Sehir Hastanesi
🇹🇷Ankara, Turkey
Medical Center OK!Clinic+LLC International Institute of Clinical Research
🇺🇦Kyiv, Ukraine
Ege University Medical Faculty
🇹🇷İzmir, Turkey
Municipal Non-profit Enterprise "City Clinical Hospital #13" of Kharkiv City Council
🇺🇦Kharkiv, Ukraine
Marmara University Pendik Training and Research Hospital
🇹🇷Istanbul, Turkey
Bezmi Alem University
🇹🇷Istanbul, Turkey
Gemini Clinical Trial Unit
🇬🇧Oxford, Oxfordshire, United Kingdom
Barts Health NHS Trust, Royal London Hospital, Ambrose King Centre
🇬🇧London, London, City Of, United Kingdom
University Hospitals Birmingham NHS Foundation Trust, Heritage Building (Queen Elizabeth Hospital)
🇬🇧Birmingham, United Kingdom
Hull Royal Infirmary
🇬🇧Hull, United Kingdom
Kings College Hospital
🇬🇧London, United Kingdom
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Galen Hepatology
🇺🇸Chattanooga, Tennessee, United States
Henry Ford Health System
🇺🇸Novi, Michigan, United States
Southern Therapy and Advanced Research, LLC (STAR)
🇺🇸Jackson, Mississippi, United States