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

NCT ID: NCT04620733

Last Updated: 2024-09-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 193 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-21
• Study Completion Date: 2023-08-11

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Seladelpar

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.

Group Type: EXPERIMENTAL

Seladelpar 10 mg

Intervention Type: DRUG

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

Seladelpar 5 mg

Intervention Type: DRUG

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

Interventions

Seladelpar 10 mg

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Seladelpar 5 mg

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.
• 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 individual or compromise the quality of the clinical study, as judged by the investigator.
• Immunosuppressant therapies.
• 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.
• Active Coronavirus Disease-2019 (COVID-19) infection during Screening.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

CymaBay Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

The Institute for Liver Health DBA Arizona Liver Health

Chandler, Arizona, United States

Arkansas Diagnostic Center

Little Rock, Arkansas, United States

Stanford University School of Medicine

Palo Alto, California, United States

California Liver Research Institute

Pasadena, California, United States

University of California, Davis Medical Center

Sacramento, California, United States

California Pacific Medical Center - Sutter Pacific Medical Foundation

San Francisco, California, United States

Covenant Metabolic Specialists, LLC

Fort Myers, Florida, United States

Florida Research Institute

Lakewood Rch, Florida, United States

Schiff Center for Liver Diseases/University of Miami

Miami, Florida, United States

Covenant Research and Clinics, LLC

Sarasota, Florida, United States

Digestive Healthcare of Georgia

Atlanta, Georgia, United States

Rush University Medical Center

Chicago, Illinois, United States

University of Chicago Hospitals

Chicago, Illinois, United States

Tulane University Health Sciences Center

New Orleans, Louisiana, United States

Mercy Medical Center

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Henry Ford Health System

Novi, Michigan, United States

MNGI Digestive Health, P.A.

Maplewood, Minnesota, United States

Southern Therapy and Advanced Research, LLC (STAR)

Jackson, Mississippi, United States

Saint Louis University

St 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

University of Rochester Medical Center

Rochester, New York, United States

Care Access Research - Lumberton

Lumberton, North Carolina, United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, United States

UPMC Center for Liver Diseases

Pittsburgh, Pennsylvania, United States

Galen Hepatology

Chattanooga, Tennessee, United States

Gastro One

Germantown, Tennessee, United States

Vanderbilt Digestive Disease Center

Nashville, Tennessee, United States

The Liver Institute at Methodist Dallas Medical Center

Dallas, Texas, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Texas Digestive Disease Consultants dba GI Alliance

Fort Hood, Texas, 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

Bon Secours Richmond Community Hospital LLC

Richmond, Virginia, United States

Liver Institute Northwest

Seattle, Washington, United States

Centro Medico Dra. De Salvo

CABA, Buenos Aires, Argentina

STAT Research S.A.

Ciudad Autonoma de Buenos Aire, Buenos Aires, Argentina

Hospital Italiano de La Plata

La Plata, Buenos Aires, Argentina

DIM CliniaPrivada

Ramos Mejía, Buenos Aires, Argentina

CINME (Centro de Investigaciones Metabolicas)

Buenos Aires, , Argentina

Hospital Italiano de Buenos Aires

Caba, , Argentina

Concord Repatriation General Hospital

Concord, New South Wales, Australia

Royal Brisbane & Women's Hospital

Herston, Queensland, Australia

Alfred Hospital

Melbourne, Victoria, Australia

The Royal Melbourne Hospital

Parkville, Victoria, Australia

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

Wels, , Austria

UZ Antwerpen

Edegem, Antwerpen, Belgium

CHU de Liège

Liège, Liège, Belgium

AZ Maria Middelares

Ghent, Oost-Vlaanderen, Belgium

Universitair Ziekenhuis Gent

Ghent, Oost-Vlaanderen, Belgium

Universitaire Ziekenhuizen Leuven

Leuven, Vlaams-Brabant, Belgium

London Health Sciences Centre

London, Ontario, Canada

University Health Network

Toronto, Ontario, Canada

Toronto Digestive Disease Associates Inc

Vaughan, Ontario, Canada

Centro Clinico Mediterraneo

La Serena, Coquimbo Region, Chile

Clinical Research Chile SpA

Valdivia, Los Ríos Region, Chile

Centro de Investigaciones Clínicas Vina del Mar

Valparaíso, , Chile

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

Ostrava, , Czechia

Aalborg Universitetshospital, Ambulatoriet for Medicinske Mave-Tarm Sygdomme

Aalborg, , Denmark

Hvidovre Hospital

Hvidovre, , Denmark

CHU de Grenoble

Grenoble, , France

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, North Rhine-Westphalia, Germany

Universitätsklinikum des Saarlandes

Homburg, Saarland, Germany

Universitatsklinikum Erlangen, Medizinische Klinik I, Gastroenterologie

Erlangen, , Germany

Universitatsklinikum Frankfurt. Medizinische Klinik I

Frankfurt am Main, , Germany

Ifi-Medizin GmbH

Hamburg, , Germany

Gastroenterologische Gemeinschaftspraxis

Herne, , Germany

Universitatsklinikum Leipzig

Leipzig, , Germany

Ippokrateio General Hospital of Athens

Athens, Attica, Greece

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

Semmelweis Egyetem

Budapest, , Hungary

Somogy Megyei Kaposi Mor Oktato Korhaz

Kaposvár, , Hungary

Liver Unit

Jerusalem, , Israel

Liver Disease Center, Sheba Medical Center

Ramat Gan, , Israel

Institute for Digestive Tract & Liver Disease

Tel Aviv, , Israel

ASST di Monza

Monza, MB, Italy

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

Ancona, , Italy

Nuovo Ospedale Civile S. Agostino-Estense di Baggiovara

Bologna, , Italy

Azienda Ospedaliero Universitaria Careggi

Florence, , Italy

Azienda Ospedaliera Universita Padova

Padua, , Italy

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone

Palermo, , Italy

Consultorio de la Doctora Maria Sarai Gonzalez Huezo

Metepec, , Mexico

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

Mexico City, , Mexico

Consultorio Medico - Distrito Federal

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

Uniwersyteckie Centrum Kliniczne Im.

Katowice, , Poland

ID Clinic Akradiusz Pisula

Mysłowice, , Poland

Fundeni Clinical Institute

Bucharest, , Romania

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, , Russia

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

Moscow, , Russia

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

Saint Petersburg, , Russia

LLC Medical Company "Hepatolog"

Samara, , Russia

Stavropol state medical university

Stavropol, , Russia

Ulyanovsk Regional Clinical Hospital

Ulyanovsk, , Russia

Inje University Busan Paik Hospital

Busan, Busan Gwangyeogsi, South Korea

Soon Chun Hyang University Hospital Bucheon

Bucheon-si, Gyeonggido, South Korea

Pusan National University Hospital

Busan, , South Korea

Kyungpook National University Hospital

Daegu, , South Korea

Seoul National University Bundang Hospital

Gyeonggi-do, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Severance Hospital Yonsei University Health System - PPDS

Soeul, , South Korea

Hospital Universitario German Trias i Pujol

Badalona, Barcelona, Spain

Hospital Universitario Margues de Valdecilla

Santander, Cantabria, Spain

Hospital Universitario Virgen de la Victoria

Málaga, Malaga, Spain

Hospital Universitario Vall D'Hebron

Barcelona, , Spain

Hospital Clinic de Barcelona

Barcelona, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

University of Zurich, Gastroenterology and Hepatology

Zurich, , Switzerland

Ankara Gazi University Faculty of Medicine Hospital

Ankara, , Turkey (Türkiye)

Ankara Sehir Hastanesi

Ankara, , Turkey (Türkiye)

Bezmi Alem University

Istanbul, , Turkey (Türkiye)

Marmara University Pendik Training and Research Hospital

Istanbul, , Turkey (Türkiye)

Ege University Medical Faculty

Izmir, , Turkey (Türkiye)

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

Kharkiv, , Ukraine

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

Kyiv, , Ukraine

University Hospitals Plymouth NHS Trust

Plymouth, Devon, United Kingdom

Portsmouth Hospitals NHS Trust

Portsmouth, Hampshire, United Kingdom

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

London, London, City of, United Kingdom

Queen's Medical Centre

Nottingham, Nottinghamshire, United Kingdom

Gemini Clinical Trial Unit

Oxford, Oxfordshire, 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

Countries

United States; Argentina; Australia; Austria; Belgium; Canada; Chile; Czechia; Denmark; France; Germany; Greece; Hungary; Israel; Italy; Mexico; New Zealand; Poland; Romania; Russia; South Korea; Spain; Switzerland; Turkey (Türkiye); Ukraine; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 38381664 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2020-004348-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CB8025-32048

Identifier Type: -

Identifier Source: org_study_id