Clinical trial NCT03301506: Seladelpar in Subjects With Primary Biliary Cholangitis (PBC)
Official title: ASSURE: An Open Label Long-Term Study to Evaluate the Safety and Tolerability of Seladelpar in Subjects With Primary Biliary Cholangitis (PBC)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Primary Biliary Cirrhosis
Keywords: PBC
Primary Biliary Cholangitis (PBC)
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2017-10-04
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)

Eligibility criteria: Inclusion Criteria:

1. Must have given written informed consent (signed and dated)
2. Participated in a PBC study with seladelpar
3. 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:

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.

1. Treatment-related adverse event (AE) leading to study drug discontinuation in a previous PBC study with seladelpar
2. 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)
3. AST or ALT above 3 × the upper limit of normal (ULN)
4. Total bilirubin above 2 × ULN
5. 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.
6. 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)
7. eGFR ≤45 mL/min/1.73 m2 (calculated by MDRD formula)
8. Auto-immune hepatitis
9. Primary sclerosing cholangitis
10. Known history of alpha-1-antitrypsin deficiency
11. Known history of chronic viral hepatitis
12. For females, pregnancy or breast-feeding
13. 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
14. Current use of fibrates or use of fibrates within 3 months prior to Screening
15. Current use of obeticholic acid or use of obeticholic acid within 3 months prior to Screening
16. Use of an experimental or unapproved treatment for PBC within 3 months prior to Screening
17. 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
18. Treatment with any other investigational therapy or medical device within 30 days or within 5 half-lives, whatever is longer, prior to Screening
19. 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
20. Immunosuppressant therapies (e.g., cyclosporine, tacrolimus, anti-TNF or other immunosuppressive biologics)
21. 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
22. Positive for:

    1. Hepatitis B, defined as the presence of hepatitis B surface antigen
    2. Hepatitis C, defined as the presence of hepatitis C virus ribonucleic acid (RNA)
    3. Human immunodeficiency virus (HIV) antibody
23. Active COVID-19 infection during screening

Primary outcomes:
measure: Treatment emergent adverse events (TEAEs) (National Cancer Institute {NCI} Common Terminology Criteria for Adverse Events {CTCAE} Version 5.0), biochemistry and hematology results
timeFrame: Through study completion, up to 60 Months
Secondary outcomes:
measure: Death
timeFrame: 60 Months
measure: Liver transplantation
timeFrame: 60 Months
measure: Change in MELD
timeFrame: 60 Months
measure: Ascites
timeFrame: 60 Months
measure: Hospitalization for variceal bleeding
timeFrame: 60 Months
measure: Hospitalization for hepatic encephalopathy
timeFrame: 60 Months
measure: Hospitalization for spontaneous bacterial peritonitis
timeFrame: 60 Months
measure: Response on composite endpoint
timeFrame: 60 Months
measure: Response on composite endpoint
timeFrame: 60 Months
measure: Normalization of ALP
timeFrame: 60 Months
measure: Laboratory Value: Serum Alkaline Phosphatase (ALP)
timeFrame: Through study completion, up to 60 Months
measure: Laboratory Value: Aspartate Aminotransferase (AST)
timeFrame: Through study completion, up to 60 Months
measure: Laboratory Value: Alanine Aminotransferase (ALT)
timeFrame: Through study completion, up to 60 Months
measure: Laboratory Value: Gamma-glutamyl Transferase (GGT)
timeFrame: Through study completion, up to 60 Months
measure: Laboratory Value: Bilirubin - Total Bilirubin
timeFrame: Through study completion, up to 60 Months
measure: Laboratory Value: Bilirubin - Conjugated Bilirubin
timeFrame: Through study completion, up to 60 Months
measure: Laboratory Value: Bilirubin - Unconjugated Bilirubin
timeFrame: Through study completion, up to 60 Months
Other outcomes:
Locations:
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
state: California
city: Aurora
country: United States
facility: University of Colorado - Denver - PPDS
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Fort Myers
country: United States
facility: Covenant Research Fort Myers
state: Florida
city: Lakewood Ranch
country: United States
facility: Florida Digestive Health Specialist
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Sarasota
country: United States
facility: Covenant Research, LLC
state: Florida
city: Atlanta
country: United States
facility: Digestive Healthcare of Georgia PC
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Hospitals
state: Illinois
city: New Orleans
country: United States
facility: East Jefferson General Hospital
state: Louisiana
city: Baltimore
country: United States
facility: Mercy Medical Center (Baltimore)
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center - 330 Brookline Ave
state: Massachusetts
city: Novi
country: United States
facility: Henry Ford Health System
state: Michigan
city: Minneapolis
country: United States
facility: MNGI Digestive Health PA-Plymouth
state: Minnesota
city: Jackson
country: United States
facility: Southern Therapy and Advanced Research LLC
state: Mississippi
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: New York
country: United States
facility: NYU Langone Medical Center
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 - PPDS
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Bethlehem
country: United States
facility: Northeast Clinical Research Center, LLC
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Health Milton S. Hershey Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Chattanooga
country: United States
facility: Galen Medical Group
state: Tennessee
city: Cordova
country: United States
facility: Gastro One-8110 Walnut Run Rd
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Dallas
country: United States
facility: Liver Institute at Methodist Dallas
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: San Antonio
country: United States
facility: The Texas Liver Institute - 607 Camden St
state: Texas
city: San Antonio
country: United States
facility: Pinnacle Clinical Research, PLLC
state: Texas
city: Newport News
country: United States
facility: Maryview Hospital Inc., d/b/a Bon Secours Liver Institute of Hampton Roads
state: Virginia
city: Richmond
country: United States
facility: Bon Secours Richmond Community Hospital, Inc. d/b/a Bon Secours Liver Institute of Richmond
state: Virginia
city: Seattle
country: United States
facility: Liver Institute Northwest, PLLC
state: Washington
city: Balvanera
country: Argentina
facility: CINME S.A. - Centro de Investigaciones Metabólicas-Viamonte 2278
city: Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: El Palomar
country: Argentina
facility: DIM Clínica Privada
city: La Plata
country: Argentina
facility: Hospital Italiano de La Plata
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Wels
country: Austria
facility: Klinikum Wels-Grieskirchen GmbH - Standort Wels
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Calgary
country: Canada
facility: University of Calgary Medicine
city: Toronto
country: Canada
facility: Toronto General Hospital
city: La Serena
country: Chile
facility: Centro Clinico Mediterraneo
city: Ostrava
country: Czechia
facility: Fakultni nemocnice Ostrava
city: Lyon
country: France
facility: Hospices Civils de Lyon - Hôpital de La Croix Rousse
city: Paris
country: France
facility: AP-HP - Hôpital Saint Antoine
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Erlangen
country: Germany
facility: Universitatsklinkum Erlangen-Ulmenweg 18
city: Hamburg
country: Germany
facility: ifi-Institute for Interdisciplinary Medicine
city: Herne
country: Germany
facility: Gastroenterologische Gemeinschaftspraxis Herne
city: Kiel
country: Germany
facility: Gastroenterologisch Hepatologisches Zentrum Kiel - Preetzer Chaussee 134
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Larisa
country: Greece
facility: University General Hospital of Larissa
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Kaposvár
country: Hungary
facility: Somogy Varmegyei Kaposi Mor Oktato Korhaz
city: Haifa
country: Israel
facility: Carmel Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center- Ein Kerem - PPDS
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center Ichilov - PPDS
city: Tel-Aviv
country: Israel
facility: The Chaim Sheba Medical Center - PPDS
city: Modena
country: Italy
facility: Azienda Ospedaliero-Universitaria di Modena - Ospedale Civile di Baggiovara
city: Palermo
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone-Palermo-Piazza Delle Cliniche 2
city: Rozzano
country: Italy
facility: Fondazione IRCCS San Gerardo dei Tintori
city: Bucheon-Si
country: Korea, Republic of
facility: Soon Chun Hyang University Hospital Bucheon
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Songpa-Gu
country: Korea, Republic of
facility: Asan Medical Center
city: Metepec
country: Mexico
facility: Consultorio de la Doctora Maria Sarai Gonzalez Huezo
city: Roma Norte
country: Mexico
facility: Consultorio Medico - Distrito Federal
city: Nijmegen
country: Netherlands
facility: Radboud Universitair Medisch Centrum
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Dunedin
country: New Zealand
facility: Dunedin Hospital
city: Katowice
country: Poland
facility: Uniwersyteckie Centrum Kliniczne Im. Prof. K. Gibinskiego Slaskiego Uniwersytetu Medycznego w Katowi
city: Myslowice
country: Poland
facility: ID Clinic Arkadiusz Pisula
city: Bucharest
country: Romania
facility: Fundeni Clinical Institute
city: Badalona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron - PPDS
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Horcajo de la Sierra
country: Spain
facility: Hospital Universitario La Paz - PPDS
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Zurich
country: Switzerland
facility: Universitätsspital Zürich
city: Ankara
country: Turkey
facility: Gazi University Faculty of Medicine
city: Bornova
country: Turkey
facility: Ege Universitesi Tip Fakultesi Hastanesi
city: Cankaya
country: Turkey
facility: Ankara Bilkent City Hospital
city: Maltepe
country: Turkey
facility: Marmara University Pendik Training and Research Hospital
city: Topkapı
country: Turkey
facility: Bezmialem Vakif Universitesi Tip Fakultesi Hastanesi
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital Birmingham
city: Hull
country: United Kingdom
facility: Hull Royal Infirmary
city: London
country: United Kingdom
facility: Barts Health NHS Trust, Royal London Hospital, Ambrose King Centre
city: London
country: United Kingdom
facility: King's College Hospital
city: Newcastle Upon Tyne
country: United Kingdom
facility: The Newcastle Upon Tyne Hospitals NHS Foundation Trust
city: Nottingham
country: United Kingdom
facility: Queen's Medical Centre
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Portsmouth
country: United Kingdom
facility: Queen Alexandra Hospital
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: