Seladelpar in Subjects With Primary Biliary Cholangitis (PBC)

Primary Biliary Cirrhosis Clinical Trial

Official title:

ASSURE: An Open Label Long-Term Study to Evaluate the Safety and Tolerability of Seladelpar in Subjects With Primary Biliary Cholangitis (PBC)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03301506
• Other study ID #: CB8025-31731-RE
• Status: Recruiting
• Phase: Phase 3
• Start date: December 12, 2017
• Est. completion date: December 2025

Study information

• Verified date: August 2023
• Source: CymaBay Therapeutics, Inc.
• Contact: Barry Crittenden, MD
• Phone: 510-293-8800
• Email: medinfo[@]cymabay.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

An Open Label Long-Term Study to Evaluate the Safety and Tolerability of Seladelpar in Subjects with Primary Biliary Cholangitis (PBC)

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 information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: December 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 seladelpar discontinuation in a previous PBC study with seladelpar (MBX-8025)

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)

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

Related Conditions & MeSH terms

• Cholangitis
• Liver Cirrhosis, Biliary
• Primary Biliary Cirrhosis

Intervention

Drug:
• Seladelpar 5 mg Capsule
Subjects will be assigned to a treatment group if tolerability issues noted in the previous study.
• Seladelpar 10 mg Capsule
Subjects will be assigned to a treatment group unless there are tolerability issues.

Locations

Country	Name	City	State
Argentina	Hospital Italiano de Buenos Aries	Ciudad Autonoma de Buenos Aire	Buenos Aires
Argentina	CINME (Centro de Investigaciones Metabolicas	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	Hospital Italiano de la Plata	La Plata	Buenos Aries
Argentina	DIM Clinica Privada	Ramos Mejía	Buenos Aires
Australia	Royal Brisbane & Women's Hospital	Herston	Queensland
Australia	Alfred Hospital	Melbourne	Victoria
Australia	Royal Melbourne Hospital	Parkville
Austria	Klinikum Wels-Grieskirchen GmbH	Wels
Belgium	UZ Gent	Gent	Oost-Vlaanderen
Belgium	UZ Leuven	Leuven	Vlaams-Brabant
Canada	University of Calgary Medicine	Calgary	Alberta
Canada	Toronto General Hospital	Toronto	Ontario
Chile	Centro Clinico Mediterraneo	La Serena	Coquimbo
Czechia	Fakultni nemocnice Ostrava	Ostrava
Czechia	Interni a Kardiologicka Klinika-Oddeleni Gastroenterologie a Hepatologie	Ostrava
France	Hopital de la Croix-Rousse	Lyon
France	Hôpital Saint Antoine	Paris
Germany	Charite Universitatsmedizin Berlin, Medizinische Poliklinik	Berlin
Germany	Universitatsklinikum Erlangen, Medizinische Klink I, Gastroenterologie	Erlangen	Bayern
Germany	Ifi-Medizin GmbH	Hamburg
Germany	Gastroenterologische Gemeinschaftspraxis	Herne	Nordrhein-Westfalen
Germany	Gastroenterologisch - Hepatologisches Zentrum Kiel	Kiel	Schleswig-Holstein
Germany	Universitatsklinik Tubingen, Medizinische Klinik, Innere Medizin I	Tübingen	Baden-Wurttemberg
Greece	General University Hospital of Larissa Department of Medicine and Research Laboratory of Internal Medicine	Larissa	Thessaly
Hungary	Semmelweis Egyetem	Budapest	Ulloi
Hungary	Somogy Megyei Kaposi Mor Oktato Korhaz	Kaposvár
Israel	Carmel Medical Center	Haifa
Israel	Hadassah Medical Center - PPDS	Jerusalem
Israel	Liver Disease Center, Sheba Medical Center	Ramat Gan
Israel	Tel Aviv Sourasky Medical Center PPDS	Tel Aviv
Italy	Nuovo Ospedale Civile S. Agostino-Estense di Baggiovara	Baggiovara	Modena
Italy	ASST di Monza	Monza	MB
Italy	Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone	Palermo
Korea, Republic of	Soon Chun Hyang University Hospital Bucheon	Bucheon	Gyeonggi-do
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	Gyeonggi-do
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul
Korea, Republic of	Asan Medical Centre	Songdong	Seoul
Mexico	Consultorio Medico - Distrito Federal	Ciudad de Mexico
Mexico	Consultorio de la Doctora Maria Sarai Gonzalez Huezo	Metepec
Netherlands	Radboudumc/Research Unit MDL	Nijmegen
New Zealand	Christchurch Hospital	Christchurch	Canterbury
New Zealand	Dunedin Hospital	Dunedin	Otago
Poland	Uniwersyteckie Centrum Kliniczne im. Prof. K. Gibinskiego Slaskiego Uniwersytetu Medycznego w Katowicach, Oddzial Gastroenterologii i Hepatologii	Katowice
Poland	ID Clinic Arkadiusz Pisula	Myslowice
Romania	Fundeni Clinical Institute	Bucharest
Russian Federation	Federal State Autonomous Educational Institution of Higher Education "Peoples' Friendship University of Russia", Centre of Liver Studies	Moscow
Russian Federation	SPbGU Medical and diagnostic center of the clinic of high medical technology n.a. N.I. Pirogov	Saint Petersburg
Russian Federation	Federal state budget educational institution of high education "Stavropol state medical university"	Stavropol
Russian Federation	Ulyanovsk Regional Clinical Hospital	Ulyanovsk
Spain	Hospital Universitario Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital Universitario Vall D'Hebron	Barcelona
Spain	Hospital clinic De Barcelona	Barcelone	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Virgen de la Victoria	Málaga
Spain	Hospital Universitario Marques de Valdecilla	Santander	Cantabria
Switzerland	Universitatsspital Zurich	Zürich
Turkey	Ankara Gazi University Faculty of Medicine Hospital	Ankara
Turkey	Ankara Sehir Hastanesi, Universiteler Mahallesi	Ankara
Turkey	Bezmialem Vakif Universitesi Tip Fakultesi Hastanesi	Fatih
Turkey	Marmara University Pendik Training and Research Hospital	Istanbul
Turkey	Ege University Medical Faculty, Kazimdirik Mah	Izmir
United Kingdom	Queen Elizabeth Hospital Birmingham	Birmingham
United Kingdom	University Hospital Birmingham - Queen Elizabeth Hospital	Birmingham
United Kingdom	Hull University Teaching Hospitals NHS Trust	Hull
United Kingdom	Barts Health NHS Trust	London
United Kingdom	Kings College Hospital	London
United Kingdom	The Newcastle Upon Tyne Hospitals NHS Foundation Trust	Newcastle
United Kingdom	The Newcastle Upon Tyne Hospital NHS Foundation Trust	Newcastle Upon Tyne
United Kingdom	Queen's Medical Centre	Nottingham	Nottinghamshire
United Kingdom	Derriford Hospital	Plymouth	Devon
United Kingdom	Portsmouth Hospitals University NHS Trust	Portsmouth	Hampshire
United States	Digestive Healthcare of Georgia	Atlanta	Georgia
United States	University of Colorado	Aurora	Colorado
United States	Mercy Medical Center	Baltimore	Maryland
United States	Northeast Clinical Research Center, LLC	Bethlehem	Pennsylvania
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Galen Hepatology	Chattanooga	Tennessee
United States	The University of Chicago Institutional Review Board	Chicago	Illinois
United States	The Liver Institute at Methodist Dallas Medical Center	Dallas	Texas
United States	U.T. Southwestern Medical Center Investigation Drug Service	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	Covenant Metabolic Specialist LLC	Fort Myers	Florida
United States	Gastro One	Germantown	Tennessee
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	Baylor College of Medicine	Houston	Texas
United States	Southern Therapy and Advanced Research (STAR), LLC	Jackson	Mississippi
United States	Florida Digestive Health Specialist	Lakewood Ranch	Florida
United States	Arkansas Diagnostic Centre	Little Rock	Arkansas
United States	Northwell Health Center for Liver Diseases	Manhasset	New York
United States	MNGI Digestive Health, P.A.	Maplewood	Minnesota
United States	Schiff Center for Liver Diseases/University of Miami	Miami	Florida
United States	Vanderbilt Hepatology and Liver Transplant	Nashville	Tennessee
United States	Yale School of Medicine	New Haven	Connecticut
United States	Tulane Medical Center	New Orleans	Louisiana
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	NYU Langone Health	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Henry Ford Health System	Novi	Michigan
United States	Stanford University School of Medicine	Palo Alto	California
United States	California Liver Research Institute	Pasadena	California
United States	UPMC Center for Liver Diseases	Pittsburgh	Pennsylvania
United States	Maryview Hospital Inc	Richmond	Virginia
United States	Richmond Community Hospital LLC., d/b/a Bon Secours Liver Institute of Richmond	Richmond	Virginia
United States	University of Rochester Medical Center - PPDS	Rochester	New York
United States	University of California, Davis Medical Center	Sacramento	California
United States	Saint Louis University	Saint Louis	Missouri
United States	American Research Corporation at the Texas Liver Institute	San Antonio	Texas
United States	Pinnacle Clinical Research, PLLC	San Antonio	Texas
United States	California Pacific Medical Center- Sutter Pacific Medical Foundation	San Francisco	California
United States	Covenant Metabolic Specialist LLC	Sarasota	Florida
United States	Liver Institute Northwest	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
CymaBay Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Canada,  Chile,  Czechia,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  New Zealand,  Poland,  Romania,  Russian Federation,  Spain,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Death	Occurrence of overall death	60 Months
Secondary	Liver transplantation	Occurrence of overall liver transplantation	60 Months
Secondary	Change in MELD	MELD score = 15 for at least 2 consecutive visits	60 Months
Secondary	Ascites	Occurrence of overall ascites requiring treatment	60 Months
Secondary	Hospitalization for variceal bleeding	Hospitalization for new onset, or recurrence, of variceal bleeding	60 Months
Secondary	Hospitalization for hepatic encephalopathy	Hospitalization for new onset, or recurrence, hepatic encephalopathy (as defined by a West Haven score = 2)	60 Months
Secondary	Hospitalization for spontaneous bacterial peritonitis	Hospitalization for new onset, or recurrence, spontaneous bacterial peritonitis (confirmed by culture from diagnostic paracentesis)	60 Months
Secondary	Response on composite endpoint	Alkaline phosphate (ALP)	60 Months
Secondary	Response on composite endpoint	Total bilirubin	60 Months
Secondary	Normalization of ALP	Proportion of subjects with normalization of ALP	60 Months
Secondary	Laboratory Value: Serum Alkaline Phosphatase (ALP)	Serum Alkaline Phosphatase (ALP)	Through study completion, up to 60 Months
Secondary	Laboratory Value: Aspartate Aminotransferase (AST)	Aspartate Aminotransferase (AST)	Through study completion, up to 60 Months
Secondary	Laboratory Value: Alanine Aminotransferase (ALT)	Alanine Aminotransferase (ALT)	Through study completion, up to 60 Months
Secondary	Laboratory Value: Gamma-glutamyl Transferase (GGT)	Gamma-glutamyl Transferase (GGT)	Through study completion, up to 60 Months
Secondary	Laboratory Value: Bilirubin - Total Bilirubin	Bilirubin - Total Bilirubin	Through study completion, up to 60 Months
Secondary	Laboratory Value: Bilirubin - Conjugated Bilirubin	Bilirubin - Conjugated Bilirubin	Through study completion, up to 60 Months
Secondary	Laboratory Value: Bilirubin - Unconjugated Bilirubin	Bilirubin - Unconjugated Bilirubin	Through study completion, up to 60 Months