Seladelpar in Subjects With Primary Biliary Cholangitis (PBC)
- Conditions
- Primary Biliary Cirrhosis
- Interventions
- Registration Number
- NCT03301506
- Lead Sponsor
- Gilead Sciences
- Brief Summary
An Open Label Long-Term Study to Evaluate the Safety and Tolerability of Seladelpar in Subjects with Primary Biliary Cholangitis (PBC)
- Detailed Description
Primary:
To evaluate the long-term safety and tolerability of seladelpar
Secondary:
* To evaluate the long-term efficacy of seladelpar
* To evaluate the effect of seladelpar on patient-reported outcomes (pruritus)
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 500
- Must have given written informed consent (signed and dated)
- Participated in a PBC study with seladelpar
- Females of reproductive potential must use at least one 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 are only applicable for subjects with a seladelpar interruption greater than 4 weeks prior to Day 1 of this study and for subjects who participated in CB8025-21838 irrespective of seladelpar interruption.
-
Treatment-related adverse event (AE) leading to study drug discontinuation in a previous PBC study with seladelpar
-
A medical condition, other than PBC, that in the Investigator's opinion would preclude full participation in the study or confound its results (e.g., cancer, any active infection)
-
AST or ALT above 3 × the upper limit of normal (ULN)
-
Total bilirubin above 2 × ULN
-
MELD score ≥ 12. For subjects on anticoagulation medication, evaluation of the baseline INR, in concert with any current dose adjustments in anti-coagulant medications, will be taken into account when calculating this score. This will be done in consultation with the medical monitor.
-
Evidence of advanced PBC as defined by the Rotterdam criteria: albumin below 1× the lower limit of normal (LLN) AND total bilirubin above 1 × ULN)
-
eGFR ≤45 mL/min/1.73 m2 (calculated by MDRD formula)
-
Auto-immune hepatitis
-
Primary sclerosing cholangitis
-
Known history of alpha-1-antitrypsin deficiency
-
Known history of chronic viral hepatitis
-
For females, pregnancy or breast-feeding
-
Use of colchicine, methotrexate, azathioprine, or long-term use of systemic steroids (e.g. prednisone, prednisolone, budesonide) (>2 weeks) within 2 months prior to Screening
-
Current use of fibrates or use of fibrates within 3 months prior to Screening
-
Current use of obeticholic acid or use of obeticholic acid within 3 months prior to Screening
-
Use of an experimental or unapproved treatment for PBC within 3 months prior to Screening
-
History of malignancy diagnosed or treated, actively or within 2 years, or active evaluation for malignancy; localized treatment of squamous or non-invasive basal cell skin cancers and cervical carcinoma in-situ is allowed if appropriately treated prior to Screening
-
Treatment with any other investigational therapy or medical device within 30 days or within 5 half-lives, whatever is longer, prior to Screening
-
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
-
Immunosuppressant therapies (e.g., cyclosporine, tacrolimus, anti-TNF or other immunosuppressive biologics)
-
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
-
Positive for:
- Hepatitis B, defined as the presence of hepatitis B surface antigen
- Hepatitis C, defined as the presence of hepatitis C virus ribonucleic acid (RNA)
- Human immunodeficiency virus (HIV) antibody
-
Active COVID-19 infection during screening
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Seladelpar 5 mg Capsules Seladelpar 5 mg Capsule - Seladelpar 10 mg Capsule Seladelpar 10 mg Capsule -
- Primary Outcome Measures
Name Time Method Treatment emergent adverse events (TEAEs) (National Cancer Institute {NCI} Common Terminology Criteria for Adverse Events {CTCAE} Version 5.0), biochemistry and hematology results Through study completion, up to 60 Months
- Secondary Outcome Measures
Name Time Method Laboratory Value: Gamma-glutamyl Transferase (GGT) Through study completion, up to 60 Months Gamma-glutamyl Transferase (GGT)
Death 60 Months Occurrence of overall death
Hospitalization for variceal bleeding 60 Months Hospitalization for new onset, or recurrence, of variceal bleeding
Hospitalization for hepatic encephalopathy 60 Months Hospitalization for new onset, or recurrence, hepatic encephalopathy (as defined by a West Haven score ≥ 2)
Normalization of ALP 60 Months Proportion of subjects with normalization of ALP
Laboratory Value: Bilirubin - Unconjugated Bilirubin Through study completion, up to 60 Months Bilirubin - Unconjugated Bilirubin
Laboratory Value: Serum Alkaline Phosphatase (ALP) Through study completion, up to 60 Months Serum Alkaline Phosphatase (ALP)
Laboratory Value: Alanine Aminotransferase (ALT) Through study completion, up to 60 Months Alanine Aminotransferase (ALT)
Change in MELD 60 Months MELD score ≥ 15 for at least 2 consecutive visits
Hospitalization for spontaneous bacterial peritonitis 60 Months Hospitalization for new onset, or recurrence, spontaneous bacterial peritonitis (confirmed by culture from diagnostic paracentesis)
Response on composite endpoint 60 Months Total bilirubin
Laboratory Value: Aspartate Aminotransferase (AST) Through study completion, up to 60 Months Aspartate Aminotransferase (AST)
Laboratory Value: Bilirubin - Total Bilirubin Through study completion, up to 60 Months Bilirubin - Total Bilirubin
Liver transplantation 60 Months Occurrence of overall liver transplantation
Laboratory Value: Bilirubin - Conjugated Bilirubin Through study completion, up to 60 Months Bilirubin - Conjugated Bilirubin
Ascites 60 Months Occurrence of overall ascites requiring treatment
Trial Locations
- Locations (108)
Bezmialem Vakif Universitesi Tip Fakultesi Hastanesi
🇹🇷Topkapı, Turkey
Queen Elizabeth Hospital Birmingham
🇬🇧Birmingham, United Kingdom
Hull Royal Infirmary
🇬🇧Hull, United Kingdom
Barts Health NHS Trust, Royal London Hospital, Ambrose King Centre
🇬🇧London, United Kingdom
Marmara University Pendik Training and Research Hospital
🇹🇷Maltepe, Turkey
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
🇺🇸San Francisco, California, United States
University of Colorado - Denver - PPDS
🇺🇸Aurora, Colorado, United States
Yale University School of Medicine
🇺🇸New Haven, Connecticut, United States
Covenant Research Fort Myers
🇺🇸Fort Myers, Florida, United States
Florida Digestive Health Specialist
🇺🇸Lakewood Ranch, Florida, United States
University of Miami Miller School of Medicine
🇺🇸Miami, Florida, United States
Covenant Research, LLC
🇺🇸Sarasota, Florida, United States
Digestive Healthcare of Georgia PC
🇺🇸Atlanta, Georgia, United States
University of Chicago Hospitals
🇺🇸Chicago, Illinois, United States
East Jefferson General Hospital
🇺🇸New Orleans, Louisiana, United States
Mercy Medical Center (Baltimore)
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Hospices Civils de Lyon - Hôpital de La Croix Rousse
🇫🇷Lyon, France
Beth Israel Deaconess Medical Center - 330 Brookline Ave
🇺🇸Boston, Massachusetts, United States
Henry Ford Health System
🇺🇸Novi, Michigan, United States
MNGI Digestive Health PA-Plymouth
🇺🇸Minneapolis, Minnesota, United States
Southern Therapy and Advanced Research LLC
🇺🇸Jackson, Mississippi, United States
Saint Louis University
🇺🇸Saint Louis, Missouri, United States
NYU Langone Medical Center
🇺🇸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 - PPDS
🇺🇸Rochester, New York, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Northeast Clinical Research Center, LLC
🇺🇸Bethlehem, Pennsylvania, United States
Penn State Health Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Galen Medical Group
🇺🇸Chattanooga, Tennessee, United States
Gastro One-8110 Walnut Run Rd
🇺🇸Cordova, Tennessee, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Liver Institute at Methodist Dallas
🇺🇸Dallas, Texas, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
The Texas Liver Institute - 607 Camden St
🇺🇸San Antonio, Texas, United States
Pinnacle Clinical Research, PLLC
🇺🇸San Antonio, Texas, United States
Maryview Hospital Inc., d/b/a Bon Secours Liver Institute of Hampton Roads
🇺🇸Newport News, Virginia, United States
Bon Secours Richmond Community Hospital, Inc. d/b/a Bon Secours Liver Institute of Richmond
🇺🇸Richmond, Virginia, United States
Liver Institute Northwest, PLLC
🇺🇸Seattle, Washington, United States
CINME S.A. - Centro de Investigaciones Metabólicas-Viamonte 2278
🇦🇷Balvanera, Argentina
AP-HP - Hôpital Saint Antoine
🇫🇷Paris, France
Hospital Italiano de Buenos Aires
🇦🇷Buenos Aires, Argentina
DIM Clínica Privada
🇦🇷El Palomar, Argentina
Hospital Italiano de La Plata
🇦🇷La Plata, Argentina
Royal Brisbane and Women's Hospital
🇦🇺Herston, Queensland, Australia
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
Klinikum Wels-Grieskirchen GmbH - Standort Wels
🇦🇹Wels, Austria
UZ Gent
🇧🇪Gent, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
University of Calgary Medicine
🇨🇦Calgary, Canada
Toronto General Hospital
🇨🇦Toronto, Canada
Centro Clinico Mediterraneo
🇨🇱La Serena, Chile
Fakultni nemocnice Ostrava
🇨🇿Ostrava, Czechia
Charité - Universitätsmedizin Berlin
🇩🇪Berlin, Germany
Universitatsklinkum Erlangen-Ulmenweg 18
🇩🇪Erlangen, Germany
ifi-Institute for Interdisciplinary Medicine
🇩🇪Hamburg, Germany
Gastroenterologische Gemeinschaftspraxis Herne
🇩🇪Herne, Germany
Gastroenterologisch Hepatologisches Zentrum Kiel - Preetzer Chaussee 134
🇩🇪Kiel, Germany
Universitätsklinikum Tübingen
🇩🇪Tübingen, Germany
University General Hospital of Larissa
🇬🇷Larisa, Greece
Semmelweis Egyetem
🇭🇺Budapest, Hungary
Somogy Varmegyei Kaposi Mor Oktato Korhaz
🇭🇺Kaposvár, Hungary
Carmel Medical Center
🇮🇱Haifa, Israel
Hadassah Medical Center- Ein Kerem - PPDS
🇮🇱Jerusalem, Israel
Tel Aviv Sourasky Medical Center Ichilov - PPDS
🇮🇱Tel Aviv, Israel
The Chaim Sheba Medical Center - PPDS
🇮🇱Tel-Aviv, Israel
Azienda Ospedaliero-Universitaria di Modena - Ospedale Civile di Baggiovara
🇮🇹Modena, Italy
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone-Palermo-Piazza Delle Cliniche 2
🇮🇹Palermo, Italy
Fondazione IRCCS San Gerardo dei Tintori
🇮🇹Rozzano, Italy
Soon Chun Hyang University Hospital Bucheon
🇰🇷Bucheon-Si, Korea, Republic of
Inje University Busan Paik Hospital
🇰🇷Busan, Korea, Republic of
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Kyungpook National University Hospital
🇰🇷Daegu, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Songpa-Gu, Korea, Republic of
Consultorio de la Doctora Maria Sarai Gonzalez Huezo
🇲🇽Metepec, Mexico
Consultorio Medico - Distrito Federal
🇲🇽Roma Norte, Mexico
Radboud Universitair Medisch Centrum
🇳🇱Nijmegen, Netherlands
Christchurch Hospital
🇳🇿Christchurch, New Zealand
Dunedin Hospital
🇳🇿Dunedin, New Zealand
Uniwersyteckie Centrum Kliniczne Im. Prof. K. Gibinskiego Slaskiego Uniwersytetu Medycznego w Katowi
🇵🇱Katowice, Poland
ID Clinic Arkadiusz Pisula
🇵🇱Myslowice, Poland
Fundeni Clinical Institute
🇷🇴Bucharest, Romania
Hospital Universitario Germans Trias i Pujol
🇪🇸Badalona, Spain
Hospital Universitario Vall d'Hebron - PPDS
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario La Paz - PPDS
🇪🇸Horcajo de la Sierra, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario Virgen de la Victoria
🇪🇸Malaga, Spain
Hospital Universitario Marques de Valdecilla
🇪🇸Santander, Spain
Universitätsspital Zürich
🇨🇭Zurich, Switzerland
Gazi University Faculty of Medicine
🇹🇷Ankara, Turkey
Ege Universitesi Tip Fakultesi Hastanesi
🇹🇷Bornova, Turkey
Ankara Bilkent City Hospital
🇹🇷Cankaya, Turkey
King's College Hospital
🇬🇧London, United Kingdom
The Newcastle Upon Tyne Hospitals NHS Foundation Trust
🇬🇧Newcastle Upon Tyne, United Kingdom
Queen's Medical Centre
🇬🇧Nottingham, United Kingdom
Derriford Hospital
🇬🇧Plymouth, United Kingdom
Queen Alexandra Hospital
🇬🇧Portsmouth, United Kingdom