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

NCT04620733 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: CB8025-320482020-004348-27
• Study Type: interventional
• Target: 193
• Locations: 25 countries
• Sites: 133

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.

Conditions

Primary Biliary Cholangitis

Keywords

Primary Biliary Cholangitis (PBC); PBC

Outcome Measures

Primary Outcomes (3)

• 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

  Percentages were rounded-off.

  Month 12

• Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

  Percentages were rounded-off.

  First dose date up to last dose plus 30 days (up to 13.4 months)

• Percentage of Participants With Shift of ≥ 2 CTCAE Grades From Baseline in Treatment-emergent Laboratory Abnormalities Related to Hematology and Select Liver Biochemistry

  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.

  First dose date up to last dose (up to 13.4 months)

Secondary Outcomes (2)

• Percentage of Participants With ALP ≤1.0× ULN at Month 12

  Month 12

• Change From Baseline in Weekly Averaged Pruritus Numerical Rating Scale (NRS) in Participants With NRS ≥ 4 at Month 6

  Baseline, Month 6

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Participants will receive placebo to match seladelpar, orally, once daily, for a duration of up to 12 months.

Drug: Placebo

Seladelpar

EXPERIMENTAL

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.

Drug: Seladelpar 10 mg; Drug: Seladelpar 5 mg

Interventions

Seladelpar 10 mg DRUG

Seladelpar 10 mg one capsule daily for double-blind period, for a duration of up to 12 months

Seladelpar

Placebo DRUG

One capsule daily for double-blind period, for a duration of up to 12 months

Placebo

Seladelpar 5 mg DRUG

If down-titration needed, one capsule daily for double-blind period, for a duration of up to 12 months

Seladelpar

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have given written informed consent (signed and dated) and any authorizations required by local law.
• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (134)

The Institute for Liver Health DBA Arizona Liver Health

Chandler, Arizona, 85224, United States

Location

Arkansas Diagnostic Center

Little Rock, Arkansas, 72205, United States

Location

Stanford University School of Medicine

Palo Alto, California, 94305, United States

Location

California Liver Research Institute

Pasadena, California, 91105, United States

Location

University of California, Davis Medical Center

Sacramento, California, 95817, United States

Location

California Pacific Medical Center - Sutter Pacific Medical Foundation

San Francisco, California, 94109, United States

Location

Covenant Metabolic Specialists, LLC

Fort Myers, Florida, 33912, United States

Location

Florida Research Institute

Lakewood Rch, Florida, 34211, United States

Location

Schiff Center for Liver Diseases/University of Miami

Miami, Florida, 33136, United States

Location

Covenant Research and Clinics, LLC

Sarasota, Florida, 34240, United States

Location

Digestive Healthcare of Georgia

Atlanta, Georgia, 30309, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Chicago Hospitals

Chicago, Illinois, 60637, United States

Location

Tulane University Health Sciences Center

New Orleans, Louisiana, 70112, United States

Location

Mercy Medical Center

Baltimore, Maryland, 21202, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Henry Ford Health System

Novi, Michigan, 48377, United States

Location

MNGI Digestive Health, P.A.

Maplewood, Minnesota, 55117, United States

Location

Southern Therapy and Advanced Research, LLC (STAR)

Jackson, Mississippi, 39216, United States

Location

Saint Louis University

St Louis, Missouri, 63104, United States

Location

NYU Langone Health / NYU Grossman School of Medicine

New York, New York, 10016, United States

Location

Weill Cornell Medical College

New York, New York, 10021, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Care Access Research - Lumberton

Lumberton, North Carolina, 28358, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

UPMC Center for Liver Diseases

Pittsburgh, Pennsylvania, 15213, United States

Location

Galen Hepatology

Chattanooga, Tennessee, 37421, United States

Location

Gastro One

Germantown, Tennessee, 38138, United States

Location

Vanderbilt Digestive Disease Center

Nashville, Tennessee, 37212, United States

Location

The Liver Institute at Methodist Dallas Medical Center

Dallas, Texas, 75203, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Texas Digestive Disease Consultants dba GI Alliance

Fort Hood, Texas, 76104, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

American Research Corporation at the Texas Liver Institute

San Antonio, Texas, 78215, United States

Location

Pinnacle Clinical Research, PLLC

San Antonio, Texas, 78229, United States

Location

Bon Secours Richmond Community Hospital LLC

Richmond, Virginia, 23226, United States

Location

Liver Institute Northwest

Seattle, Washington, 98105, United States

Location

Centro Medico Dra. De Salvo

CABA, Buenos Aires, C1426ABP, Argentina

Location

STAT Research S.A.

Ciudad Autonoma de Buenos Aire, Buenos Aires, C1023AAB, Argentina

Location

Hospital Italiano de La Plata

La Plata, Buenos Aires, B1900AX, Argentina

Location

DIM CliniaPrivada

Ramos Mejía, Buenos Aires, B1704ETD, Argentina

Location

CINME (Centro de Investigaciones Metabolicas)

Buenos Aires, C1056ABJ, Argentina

Location

Hospital Italiano de Buenos Aires

Caba, C1199ABB, Argentina

Location

Concord Repatriation General Hospital

Concord, New South Wales, 2139, Australia

Location

Royal Brisbane & Women's Hospital

Herston, Queensland, 4029, Australia

Location

Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

The Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Klinikum Wels-Grieskirchen GmbH, Abteilung Fur Innere Medizin I - Gastroenterologie

Wels, 4600, Austria

Location

UZ Antwerpen

Edegem, Antwerpen, 2650, Belgium

Location

CHU de Liège

Liège, Liège, 4000, Belgium

Location

AZ Maria Middelares

Ghent, Oost-Vlaanderen, 9000, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, Oost-Vlaanderen, 9000, Belgium

Location

Universitaire Ziekenhuizen Leuven

Leuven, Vlaams-Brabant, 3000, Belgium

Location

London Health Sciences Centre

London, Ontario, N6A 5A5, Canada

Location

University Health Network

Toronto, Ontario, M5G 2C4, Canada

Location

Toronto Digestive Disease Associates Inc

Vaughan, Ontario, L4L 4Y7, Canada

Location

Centro Clinico Mediterraneo

La Serena, Coquimbo Region, 1700000, Chile

Location

Clinical Research Chile SpA

Valdivia, Los Ríos Region, 5110683, Chile

Location

Centro de Investigaciones Clínicas Vina del Mar

Valparaíso, 2540364, Chile

Location

Fakultni nemocnice Ostrava- Interni a Kardiologicka Klinika, Oddeleni gastroenterologie, hepatologie a pankreatologie

Ostrava, 708 52, Czechia

Location

Aalborg Universitetshospital, Ambulatoriet for Medicinske Mave-Tarm Sygdomme

Aalborg, 9000, Denmark

Location

Hvidovre Hospital

Hvidovre, 2650, Denmark

Location

CHU de Grenoble

Grenoble, 38043, France

Location

Hopital de la Croix-Rousse

Lyon, 69004, France

Location

Hopital Saint-Antoine - Service d'Hepato-Gastro-Enterologie -184, rue du Faubourg Saint-Antoine

Paris, 75012, France

Location

Universitätsklinikum Bonn

Bonn, North Rhine-Westphalia, 53127, Germany

Location

Universitätsklinikum des Saarlandes

Homburg, Saarland, 66421, Germany

Location

Universitatsklinikum Erlangen, Medizinische Klinik I, Gastroenterologie

Erlangen, 91054, Germany

Location

Universitatsklinikum Frankfurt. Medizinische Klinik I

Frankfurt am Main, 60590, Germany

Location

Ifi-Medizin GmbH

Hamburg, 20099, Germany

Location

Gastroenterologische Gemeinschaftspraxis

Herne, 44623, Germany

Location

Universitatsklinikum Leipzig

Leipzig, 04103, Germany

Location

Ippokrateio General Hospital of Athens

Athens, Attica, 115 27, Greece

Location

General University Hospital of Larissa Department of Medicine and Research Laboratory of internal rv1edicine, National Expertise Center of Greece in Autoimmune liver Diseases

Larissa, 41110, Greece

Location

Semmelweis Egyetem

Budapest, 1082, Hungary

Location

Somogy Megyei Kaposi Mor Oktato Korhaz

Kaposvár, 7400, Hungary

Location

Liver Unit

Jerusalem, 91120, Israel

Location

Liver Disease Center, Sheba Medical Center

Ramat Gan, 52621, Israel

Location

Institute for Digestive Tract & Liver Disease

Tel Aviv, 64239, Israel

Location

ASST di Monza

Monza, MB, 20900, Italy

Location

Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona-Umberto I G.M. Lancisi G. Salesi

Ancona, 60020, Italy

Location

Nuovo Ospedale Civile S. Agostino-Estense di Baggiovara

Bologna, 41126, Italy

Location

Azienda Ospedaliero Universitaria Careggi

Florence, 50139, Italy

Location

Azienda Ospedaliera Universita Padova

Padua, 35128, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone

Palermo, 90127, Italy

Location

Consultorio de la Doctora Maria Sarai Gonzalez Huezo

Metepec, 52140, Mexico

Location

Campeche No. 280, Int. 601 y 602, Col. Hipodromo, Cuauhtemoc

Mexico City, 06100, Mexico

Location

Consultorio Medico - Distrito Federal

Mexico City, 06700, Mexico

Location

Hospital Universitario Dr. Jose Eleuterio González

Monterrey, 64460, Mexico

Location

Gastroenterology, Christchurch Hospital

Christchurch, Canterbury, 8011, New Zealand

Location

Gastroenterology Research Unit Dunedin Hospital

Dunedin, Otago, 9016, New Zealand

Location

Uniwersyteckie Centrum Kliniczne Im.

Katowice, 40-752, Poland

Location

ID Clinic Akradiusz Pisula

Mysłowice, 41-400, Poland

Location

Fundeni Clinical Institute

Bucharest, 022328, Romania

Location

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, 111123, Russia

Location

Federal State Autonomous Educational Institution of Higher Education "Peoples' Friendship University of Russia", Centre of Liver Studies

Moscow, 117198, Russia

Location

Clinic of High Medical Technologies n.a. N.I. Pirogov

Saint Petersburg, 199034, Russia

Location

LLC Medical Company "Hepatolog"

Samara, 443045, Russia

Location

Stavropol state medical university

Stavropol, 355017, Russia

Location

Ulyanovsk Regional Clinical Hospital

Ulyanovsk, 432063, Russia

Location

Inje University Busan Paik Hospital

Busan, Busan Gwangyeogsi, 47392, South Korea

Location

Soon Chun Hyang University Hospital Bucheon

Bucheon-si, Gyeonggido, 14584, South Korea

Location

Pusan National University Hospital

Busan, 49241, South Korea

Location

Kyungpook National University Hospital

Daegu, 41944, South Korea

Location

Seoul National University Bundang Hospital

Gyeonggi-do, 13620, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Severance Hospital Yonsei University Health System - PPDS

Soeul, 03722, South Korea

Location

Hospital Universitario German Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Hospital Universitario Margues de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, Malaga, 2910, Spain

Location

Hospital Universitario Vall D'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

University of Zurich, Gastroenterology and Hepatology

Zurich, 8091, Switzerland

Location

Ankara Gazi University Faculty of Medicine Hospital

Ankara, 06560, Turkey (Türkiye)

Location

Ankara Sehir Hastanesi

Ankara, 06800, Turkey (Türkiye)

Location

Bezmi Alem University

Istanbul, 34093, Turkey (Türkiye)

Location

Marmara University Pendik Training and Research Hospital

Istanbul, 34899, Turkey (Türkiye)

Location

Ege University Medical Faculty

Izmir, 35100, Turkey (Türkiye)

Location

Municipal Non-profit Enterprise "City Clinical Hospital #13" of Kharkiv City Council

Kharkiv, 61124, Ukraine

Location

Medical Center OK!Clinic+LLC International Institute of Clinical Research

Kyiv, 0291, Ukraine

Location

University Hospitals Plymouth NHS Trust

Plymouth, Devon, PL6 8DH, United Kingdom

Location

Portsmouth Hospitals NHS Trust

Portsmouth, Hampshire, P06 3LY, United Kingdom

Location

Barts Health NHS Trust, Royal London Hospital, Ambrose King Centre

London, London, City of, E1 1RF, United Kingdom

Location

Queen's Medical Centre

Nottingham, Nottinghamshire, NG7 2UH, United Kingdom

Location

Gemini Clinical Trial Unit

Oxford, Oxfordshire, OX4 2LL, United Kingdom

Location

University Hospitals Birmingham NHS Foundation Trust, Heritage Building (Queen Elizabeth Hospital)

Birmingham, B15 2TH, United Kingdom

Location

Hull Royal Infirmary

Hull, HU3 2JZ, United Kingdom

Location

Kings College Hospital

London, SE5 9RS, United Kingdom

Location

Related Publications (1)

• Hirschfield GM, Bowlus CL, Mayo MJ, Kremer AE, Vierling JM, Kowdley KV, Levy C, Villamil A, Ladron de Guevara Cetina AL, Janczewska E, Zigmond E, Jeong SH, Yilmaz Y, Kallis Y, Corpechot C, Buggisch P, Invernizzi P, Londono Hurtado MC, Bergheanu S, Yang K, Choi YJ, Crittenden DB, McWherter CA; RESPONSE Study Group. A Phase 3 Trial of Seladelpar in Primary Biliary Cholangitis. N Engl J Med. 2024 Feb 29;390(9):783-794. doi: 10.1056/NEJMoa2312100. Epub 2024 Feb 21.

  PMID: 38381664 DERIVED

MeSH Terms

Conditions

Liver Cirrhosis, Biliary

Interventions

seladelpar

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: CymaBay Study Director
• Organization: CymaBay Therapeutics, Inc.

medinfo@cymabay.com

1-510-293-8800

Study Officials

• CymaBay Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2020
• First Posted: November 9, 2020
• Study Start: April 21, 2021
• Primary Completion: August 11, 2023
• Study Completion: August 11, 2023
• Last Updated: September 5, 2024
• Results First Posted: July 25, 2024

Record last verified: 2024-08

Locations

CZ (1); NZ (2); IL (3); DK (2); KR (9); AU (4); ES (6); PL (2); IT (6); ME (4); GB (8); UA (2); CH (1); AR (6); CL (3); FR (3); GR (2); HU (2); BE (5); CA (3); DE (7); RO (1); RU (6); TU (5); US (40)