Clinical trial NCT04620733: RESPONSE: Response to Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and an Inadequate Control to or an Intolerance to Ursodeoxycholic Acid (UDCA)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Biliary Cholangitis
Keywords: Primary Biliary Cholangitis (PBC)
PBC
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2020-11-09
Enrollment: 193
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Key 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.

Key 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.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: 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
timeFrame: Month 12
measure: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: First dose date up to last dose plus 30 days (up to 13.4 months)
measure: Percentage of Participants With Shift of ≥ 2 CTCAE Grades From Baseline in Treatment-emergent Laboratory Abnormalities Related to Hematology and Select Liver Biochemistry
timeFrame: First dose date up to last dose (up to 13.4 months)
Secondary outcomes:
measure: Percentage of Participants With ALP ≤1.0× ULN at Month 12
timeFrame: Month 12
measure: Change From Baseline in Weekly Averaged Pruritus Numerical Rating Scale (NRS) in Participants With NRS ≥ 4 at Month 6
timeFrame: Baseline, Month 6
Other outcomes:
Locations:
city: Chandler
country: United States
facility: The Institute for Liver Health DBA Arizona Liver Health
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Diagnostic Center
state: Arkansas
city: Palo Alto
country: United States
facility: Stanford University School of Medicine
state: California
city: Pasadena
country: United States
facility: California Liver Research Institute
state: California
city: Sacramento
country: United States
facility: University of California, Davis Medical Center
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center - Sutter Pacific Medical Foundation
state: California
city: Fort Myers
country: United States
facility: Covenant Metabolic Specialists, LLC
state: Florida
city: Lakewood Ranch
country: United States
facility: Florida Research Institute
state: Florida
city: Miami
country: United States
facility: Schiff Center for Liver Diseases/University of Miami
state: Florida
city: Sarasota
country: United States
facility: Covenant Research and Clinics, LLC
state: Florida
city: Atlanta
country: United States
facility: Digestive Healthcare of Georgia
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Hospitals
state: Illinois
city: New Orleans
country: United States
facility: Tulane University Health Sciences Center
state: Louisiana
city: Baltimore
country: United States
facility: Mercy Medical Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Novi
country: United States
facility: Henry Ford Health System
state: Michigan
city: Maplewood
country: United States
facility: MNGI Digestive Health, P.A.
state: Minnesota
city: Jackson
country: United States
facility: Southern Therapy and Advanced Research, LLC (STAR)
state: Mississippi
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: New York
country: United States
facility: NYU Langone Health / NYU Grossman School of Medicine
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Lumberton
country: United States
facility: Care Access Research - Lumberton
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Hershey
country: United States
facility: Penn State Milton S Hershey Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Center for Liver Diseases
state: Pennsylvania
city: Chattanooga
country: United States
facility: Galen Hepatology
state: Tennessee
city: Germantown
country: United States
facility: Gastro One
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Digestive Disease Center
state: Tennessee
city: Dallas
country: United States
facility: The Liver Institute at Methodist Dallas Medical Center
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Fort Hood
country: United States
facility: Texas Digestive Disease Consultants dba GI Alliance
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: San Antonio
country: United States
facility: American Research Corporation at the Texas Liver Institute
state: Texas
city: San Antonio
country: United States
facility: Pinnacle Clinical Research, PLLC
state: Texas
city: Richmond
country: United States
facility: Bon Secours Richmond Community Hospital LLC
state: Virginia
city: Seattle
country: United States
facility: Liver Institute Northwest
state: Washington
city: Caba
country: Argentina
facility: Centro Medico Dra. De Salvo
state: Buenos Aires
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: STAT Research S.A.
state: Buenos Aires
city: La Plata
country: Argentina
facility: Hospital Italiano de La Plata
state: Buenos Aires
city: Ramos Mejía
country: Argentina
facility: DIM CliniaPrivada
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: CINME (Centro de Investigaciones Metabolicas)
city: Caba
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane & Women's Hospital
state: Queensland
city: Melbourne
country: Australia
facility: Alfred Hospital
state: Victoria
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital
state: Victoria
city: Wels
country: Austria
facility: Klinikum Wels-Grieskirchen GmbH, Abteilung Fur Innere Medizin I - Gastroenterologie
city: Edegem
country: Belgium
facility: UZ Antwerpen
state: Antwerpen
city: Liege
country: Belgium
facility: CHU de Liège
state: Liège
city: Gent
country: Belgium
facility: AZ Maria Middelares
state: Oost-Vlaanderen
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
state: Oost-Vlaanderen
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven
state: Vlaams-Brabant
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Vaughan
country: Canada
facility: Toronto Digestive Disease Associates Inc
state: Ontario
city: La Serena
country: Chile
facility: Centro Clinico Mediterraneo
state: Coquimbo
city: Valdivia
country: Chile
facility: Clinical Research Chile SpA
state: Los Ríos
city: Valparaíso
country: Chile
facility: Centro de Investigaciones Clínicas Vina del Mar
city: Ostrava
country: Czechia
facility: Fakultni nemocnice Ostrava- Interni a Kardiologicka Klinika, Oddeleni gastroenterologie, hepatologie a pankreatologie
city: Aalborg
country: Denmark
facility: Aalborg Universitetshospital, Ambulatoriet for Medicinske Mave-Tarm Sygdomme
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital
city: Grenoble
country: France
facility: CHU de Grenoble
city: Lyon
country: France
facility: Hopital de la Croix-Rousse
city: Paris
country: France
facility: Hopital Saint-Antoine - Service d'Hepato-Gastro-Enterologie -184, rue du Faubourg Saint-Antoine
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
state: Nordrhein-Westfalen
city: Homburg
country: Germany
facility: Universitätsklinikum des Saarlandes
state: Saarland
city: Erlangen
country: Germany
facility: Universitatsklinikum Erlangen, Medizinische Klinik I, Gastroenterologie
city: Frankfurt am main
country: Germany
facility: Universitatsklinikum Frankfurt. Medizinische Klinik I
city: Hamburg
country: Germany
facility: Ifi-Medizin GmbH
city: Herne
country: Germany
facility: Gastroenterologische Gemeinschaftspraxis
city: Leipzig
country: Germany
facility: Universitatsklinikum Leipzig
city: Athens
country: Greece
facility: Ippokrateio General Hospital of Athens
state: Attiki
city: Larissa
country: Greece
facility: General University Hospital of Larissa Department of Medicine and Research Laboratory of internal rv1edicine, National Expertise Center of Greece in Autoimmune liver Diseases
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Kaposvár
country: Hungary
facility: Somogy Megyei Kaposi Mor Oktato Korhaz
city: Jerusalem
country: Israel
facility: Liver Unit
city: Ramat Gan
country: Israel
facility: Liver Disease Center, Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Institute for Digestive Tract & Liver Disease
city: Monza
country: Italy
facility: ASST di Monza
state: MB
city: Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona-Umberto I G.M. Lancisi G. Salesi
city: Bologna
country: Italy
facility: Nuovo Ospedale Civile S. Agostino-Estense di Baggiovara
city: Firenze
country: Italy
facility: Azienda Ospedaliero Universitaria Careggi
city: Padova
country: Italy
facility: Azienda Ospedaliera Universita Padova
city: Palermo
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital
state: Busan Gwangyeogsi
city: Bucheon-si
country: Korea, Republic of
facility: Soon Chun Hyang University Hospital Bucheon
state: Gyeonggido
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Soeul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System - PPDS
city: Ciudad de Mexico
country: Mexico
facility: Consultorio Medico - Distrito Federal
city: Metepec
country: Mexico
facility: Consultorio de la Doctora Maria Sarai Gonzalez Huezo
city: Mexico City
country: Mexico
facility: Campeche No. 280, Int. 601 y 602, Col. Hipodromo, Cuauhtemoc
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr. Jose Eleuterio González
city: Christchurch
country: New Zealand
facility: Gastroenterology, Christchurch Hospital
state: Canterbury
city: Dunedin
country: New Zealand
facility: Gastroenterology Research Unit Dunedin Hospital
state: Otago
city: Katowice
country: Poland
facility: Uniwersyteckie Centrum Kliniczne Im.
city: Mysłowice
country: Poland
facility: ID Clinic Akradiusz Pisula
city: Bucharest
country: Romania
facility: Fundeni Clinical Institute
city: Moscow
country: Russian Federation
facility: 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
city: Moscow
country: Russian Federation
facility: Federal State Autonomous Educational Institution of Higher Education "Peoples' Friendship University of Russia", Centre of Liver Studies
city: Saint Petersburg
country: Russian Federation
facility: Clinic of High Medical Technologies n.a. N.I. Pirogov
city: Samara
country: Russian Federation
facility: LLC Medical Company "Hepatolog"
city: Stavropol
country: Russian Federation
facility: Stavropol state medical university
city: Ulyanovsk
country: Russian Federation
facility: Ulyanovsk Regional Clinical Hospital
city: Badalona
country: Spain
facility: Hospital Universitario German Trias i Pujol
state: Barcelona
city: Santander
country: Spain
facility: Hospital Universitario Margues de Valdecilla
state: Cantabria
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
state: Malaga
city: Barcelona
country: Spain
facility: Hospital Universitario Vall D'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Zürich
country: Switzerland
facility: University of Zurich, Gastroenterology and Hepatology
city: Ankara
country: Turkey
facility: Ankara Gazi University Faculty of Medicine Hospital
city: Ankara
country: Turkey
facility: Ankara Sehir Hastanesi
city: Istanbul
country: Turkey
facility: Bezmi Alem University
city: Istanbul
country: Turkey
facility: Marmara University Pendik Training and Research Hospital
city: İzmir
country: Turkey
facility: Ege University Medical Faculty
city: Kharkiv
country: Ukraine
facility: Municipal Non-profit Enterprise "City Clinical Hospital #13" of Kharkiv City Council
city: Kyiv
country: Ukraine
facility: Medical Center OK!Clinic+LLC International Institute of Clinical Research
city: Plymouth
country: United Kingdom
facility: University Hospitals Plymouth NHS Trust
state: Devon
city: Portsmouth
country: United Kingdom
facility: Portsmouth Hospitals NHS Trust
state: Hampshire
city: London
country: United Kingdom
facility: Barts Health NHS Trust, Royal London Hospital, Ambrose King Centre
state: London, City Of
city: Nottingham
country: United Kingdom
facility: Queen's Medical Centre
state: Nottinghamshire
city: Oxford
country: United Kingdom
facility: Gemini Clinical Trial Unit
state: Oxfordshire
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust, Heritage Building (Queen Elizabeth Hospital)
city: Hull
country: United Kingdom
facility: Hull Royal Infirmary
city: London
country: United Kingdom
facility: Kings College Hospital
Study officials:
affiliation: Gilead Sciences
name: CymaBay Study Director
role: STUDY_DIRECTOR
References: