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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03602560
Other study ID # CB8025-31735
Secondary ID
Status Completed
Phase Phase 3
First received
Last updated
Start date October 1, 2018
Est. completion date February 16, 2020

Study information

Verified date July 2022
Source CymaBay Therapeutics, Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

A 52-week, placebo-controlled, randomized, Phase 3 study to evaluate the safety and efficacy of seladelpar in subjects with primary biliary cholangitis (PBC) and an inadequate response to or intolerance to ursodeoxycholic acid (UDCA) The participants might enter the ongoing open-label safety study (NCT03301506) following this double-blind study.


Description:

Primary: - To evaluate the safety and effect on cholestasis of two seladelpar regimens (5 mg/day titrated to 10 mg/day and 10 mg/day) over 52 weeks of treatment compared to placebo Key Secondary: - To evaluate the effect of seladelpar on normalization of alkaline phosphatase (AP) levels - To evaluate the effect of seladelpar on pruritus


Recruitment information / eligibility

Status Completed
Enrollment 265
Est. completion date February 16, 2020
Est. primary completion date February 16, 2020
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) and any authorizations required by local law 2. 18 to 75 years old (inclusive) 3. Male or female with a diagnosis of PBC, by at least two of the following criteria: - History of AP above ULN for at least six months - Positive anti-mitochondrial antibody (AMA) titers (>1/40 on immunofluorescence or M2 positive by enzyme linked immunosorbent assay [ELISA]) or positive PBC-specific antinuclear antibodies - Documented liver biopsy result consistent with PBC 4. On a stable and recommended dose of UDCA for the past twelve months OR intolerant to UDCA (last dose of UDCA > 3 months prior to Screening) 5. AP = 1.67 × ULN 6. 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: 1. Previous exposure to 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 above 3 × ULN 4. ALT above 3 × ULN 5. Total bilirubin above 2.0 × ULN 6. Advanced PBC as defined by the Rotterdam criteria (albumin below LLN AND total bilirubin above 1 × ULN) 7. Creatine kinase (CK) above 1.0 × ULN 8. eGFR below 60 mL/min/1.73 m2 (calculated by MDRD formula) 9. International normalized ratio (INR) above 1.0 × ULN 10. Platelet count below 100 × 103/µL 11. Presence of clinically significant hepatic decompensation, including: - History of liver transplantation, current placement on liver transplantation list, or current MELD score = 15 - Complications of portal hypertension, including known esophageal varices, history of variceal bleeds or related interventions (e.g., transjugular intrahepatic portosystemic shunt placement), relevant ascites, hepatic encephalopathy - Cirrhosis with complications, including history or presence of spontaneous bacterial peritonitis 12. Other chronic liver diseases: - Current features of auto-immune hepatitis as determined by the investigator based on immunoserology, liver biochemistry and histology - Primary sclerosing cholangitis determined by presence of diagnostic cholangiographic findings - History or clinical evidence of alcoholic liver disease - History or clinical evidence of alpha-1-antitrypsin deficiency - Biopsy confirmed nonalcoholic steatohepatitis - History or evidence of Gilbert' Syndrome with elevated total bilirubin - History or evidence of hemochromatosis - Hepatitis B defined as presence of hepatitis B surface antigen (HBsAg) - Hepatitis C defined as presence of HCV RNA 13. Known history of HIV 14. Evidence of significant alcohol consumption 15. Evidence of drug abuse 16. Subjects with inadequate response to obeticholic acid (OCA) or intolerance to OCA: OCA must be discontinued 30 days prior to Screening 17. Use of colchicine, methotrexate, azathioprine, or long-term systemic corticosteroids (> 2 weeks) within two months prior to Screening 18. Use of fibrates within 30 days prior to Screening 19. Use of simvastatin within 7 days prior to Screening 20. Use of an experimental or unapproved treatment for PBC within 30 days prior to Screening 21. Use of experimental or unapproved immunosuppressant within 30 days prior to Screening 22. Treatment with any other investigational therapy or device within 30 days or within five half-lives, whatever is longer, prior to Screening 23. For females, pregnancy or breast-feeding 24. 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

Study Design


Intervention

Drug:
seladelpar 5-10 mg
Seladelpar 5 mg for 6 months and then titrating up to 10 mg based on tolerability and response for remainder of double-blind period. After completion of the 1-year double-blind period subjects will be offered the opportunity to enter an open label long term safety study. Subjects will continue the seladelpar dose (5 or 10 mg) received during the double-blinded study
seladelpar 10 mg
Seladelpar 10 mg for double-blind period. After completion of the 1-year double-blind period subjects will be offered the opportunity to enter an open label safety study. Subjects will continue the seladelpar dose (10 mg) received during the double-blinded study
Placebo
One capsule daily for double-blind period. After completion of the 1-year double-blind period subjects will be offered the opportunity to enter an open label long term safety study. Subjects on placebo will be re-randomized to initiate seladelpar at 5 or 10 mg once daily

Locations

Country Name City State
Argentina Fundación Sanatorio Güemes Buenos Aires Ciudad Autónoma De BuenosAires
Argentina Hospital Universitario Austral Pilar Buenos Aires
Argentina DIM Clínica Privada Ramos Mejía
Argentina Hospital Provincial Del Centenario Rosario Santa Fe
Australia St Vincents Hospital Melbourne Fitzroy Victoria
Australia The Canberra Hospital Garran Australian Capital Territory
Australia Royal Brisbane & Women's Hospital Herston Queensland
Australia Royal Melbourne Hospital Parkville Victoria
Australia Royal Perth Hospital Perth Western Australia
Austria LKH-Universitätsklinikum Klinikum Graz Graz
Austria Salzburger Landeskliniken Salzburg
Austria Medizinische Universitat Wien Vienna Wien
Austria Klinikum Wels-Grieskirchen GmbH Wels
Belgium UZ Antwerpen Edegem Antwerpen
Belgium UZ Gent Gent Oost-Vlaanderen
Belgium UZ Leuven Leuven Vlaams Brabant
Canada University of Calgary Medicine Calgary Alberta
Canada McGill University Health Centre (MUHC) Montréal Quebec
Canada University Health Network Toronto Ontario
Canada Toronto Digestive Disease Associates Inc Vaughan Ontario
Canada University of Manitoba Winnipeg Manitoba
Chile Centro Clinico Mediterraneo La Serena
Chile Pontificia Universidad Catolica de Chile Santiago Región-MetropolitanadeSantiago
Chile Centro de Investigaciones Clínicas Vina del Mar Viña Del Mar
France Hôpital Jean Verdier Bondy
France CHU de GRENOBLE Grenoble
France Hôpital Saint Antoine Paris
Germany Charité - Universitätsmedizin Berlin Berlin
Germany Universitätsklinikum Erlangen Erlangen
Germany ifi-Institute for Interdisciplinary Medicine Hamburg
Germany Gastroenterologische Gemeinschaftspraxis Herne Herne Nordrhein-Westfalen
Germany Gastroenterologisch Hepatologisches Zentrum Kiel Kiel Schleswig-Holstein
Germany Uniklinik Köln Köln Nordrhein-Westfalen
Germany Universitatsklinikum Leipzig Leipzig
Germany Universitätsklinikum Tübingen Tübingen Baden-Württemberg
Greece University General Hospital of Heraklion Heraklion
Greece University General Hospital of Larissa Larissa
Greece University General Hospital of Patras Patras
Hungary Budai Hepatológiai Centrum Budapest
Hungary Debreceni Egyetem Klinikai Kozpont Debrecen
Hungary Somogy Megyei Kaposi Mór Oktató Kórház Kaposvár
Hungary Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont Szeged Csongrád
Israel Hillel Yaffe Medical Center Hadera
Israel Carmel Medical Center Haifa
Israel Rambam Health Corporation Haifa
Israel Hadassah Medical Center Jerusalem
Israel The Galilli Medical Center Nahariya
Israel Chaim Sheba Medical Center Ramat Gan
Israel Kaplan Medical Center Re?ovot
Israel Tel Aviv Sourasky Medical Center Tel Aviv
Italy Azienda Ospedaliera Universitaria Careggi Firenze
Italy ASST Santi Paolo e Carlo - Azienda Universitaria-Polo Universitario San Paolo Milano
Italy Ospedale Civile di Baggiovara Modena
Italy Azienda Ospedaliera Di Padova Padova
Italy ASST di Monza - Azienda Ospedaliera San Gerardo Rozzano
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-si Gyeonggido
Korea, Republic of Gangnam Severance Hospital, Yonsei University Health System Seoul
Korea, Republic of Inje University Ilsan Paik Hospital Seoul
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
Mexico Consultorio Medico - Distrito Federal Ciudad de Mexico
Mexico Consultorio de la Doctora Maria Sarai Gonzalez Huezo Metepec
Mexico Centro de Diabetes y Obesidad Graber Pachuca de Soto Hidalgo
Netherlands Radboud Universitair Medisch Centrum Nijmegen Gelderland
New Zealand Christchurch Hospital Christchurch South Island
New Zealand Dunedin Hospital Dunedin South Island
New Zealand Waikato Hospital Hamilton
Poland Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza w Bydgoszczy Bydgoszcz Kujawsko-pomorskie
Poland Samodzielny Publiczny Szpital Kliniczny Nr 7 Slaskiego Uniwersytetu Medycznego w Katowicach Katowice Slaskie
Poland Wojewodzki Szpital Zespolony w Kielcach Kielce
Poland SP ZOZ Szpital Uniwersytecki w Krakowie Kraków
Poland ID Clinic Myslowice
Poland Centrum Onkologii Instytut im. Marii Sklodowskiej-Curie Warszawa Mazowieckie
Romania Colentina Clinical Hospital Bucharest
Romania Fundeni Clinical Institute Bucharest
Romania Sana Monitoring SRL Bucharest
Romania Pius Brinzeu Emergency Clinical County Hospital Timisoara Timis
Russian Federation Peoples Friendship University of Russia Moscow Moskva
Russian Federation City Hospital #31 St. Petersburg
Russian Federation Ulyanovsk Regional Clinical Hospital Ulyanovsk
Serbia Clinical Hospital Centar Zvezdara Belgrade
Serbia KBC Zemun Belgrade
Spain Hospital Clinic de Barcelona Barcelona
Spain Hospital Universitario Germans Trias i Pujol Barcelona
Spain Hospital Universitario Vall d'Hebrón - PPDS Barcelona
Spain Hospital Universitario La Paz Madrid
Spain Hospital Universitario Ramon y Cajal Madrid
Spain Hospital Universitario Puerta de Hierro - Majadahonda Majadahonda Madrid
Spain Hospital Universitario Virgen de la Victoria Málaga
Spain Hospital Universitario Virgen del Rocio Sevilla
Spain Hospital Clinico Universitario de Valencia Valencia
Spain Hospital Universitari i Politecnic La Fe de Valencia Valencia
United Kingdom University Hospital Birmingham Birmingham
United Kingdom Hull and East Yorkshire Hospitals NHS Trust Hull
United Kingdom Barts Health NHS Trust, Royal London Hospital, Ambrose King Centre London
United Kingdom Kings College Hospital London
United Kingdom Royal Free London NHS Foundation Trust London
United Kingdom The Newcastle Upon Tyne Hospital NHS Foundation Trust Newcastle
United Kingdom University of Nottingham Nottingham
United Kingdom Plymouth Hospitals NHS Trust Plymouth
United Kingdom Queen Alexandra Hospital Portsmouth Hampshire
United Kingdom Singleton Hospital Swansea
United States Asheville Gastroenterology Associates, a Division of Digestive Health Partners, P.A. Asheville North Carolina
United States Digestive Healthcare of Georgia Atlanta Georgia
United States Univeristy of Colorado Denver and Hospital Aurora Colorado
United States Northeast Clinical Research Center, LLC Bethlehem Pennsylvania
United States Excel Medical Clinical Trials, LLC Boca Raton Florida
United States Beth Israel Deaconess Medical Center Boston Massachusetts
United States Massachusetts General Hospital Boston Massachusetts
United States Institute for Liver Health Chandler Arizona
United States University of Chicago Medical Center Chicago Illinois
United States UH Cleveland Medical Center Cleveland Ohio
United States Liver Institute at Methodist Dallas Dallas Texas
United States University of Texas Southwestern Medical Center Dallas Texas
United States Duke University Medical Center Durham North Carolina
United States Texas Digestive Disease Consultants Fort Worth Texas
United States Gastro One Germantown Tennessee
United States Penn State Milton S Hershey Medical Center Hershey Pennsylvania
United States American Research Corporation Houston Texas
United States Baylor College of Medicine Houston Texas
United States Indianapolis Gastroenterology Research Foundation Indianapolis Indiana
United States Southern Therapy and Advance Research (STAR) LLC Jackson Mississippi
United States Kansas City Research Institute Kansas City Missouri
United States University of Kansas Hospital Kansas City Kansas
United States GIA Clinical Trials, LLC Knoxville Tennessee
United States Florida Reserach Institute Lakewood Ranch Florida
United States Cedars Sinai Medical Center Los Angeles California
United States Minnesota Gastroenterlogy, P.A. Maplewood Minnesota
United States Schiff Center for Liver Diseases University of Miami Miami Florida
United States University of Minnesota Medical Center, Fairview Minneapolis Minnesota
United States Intermountain Medical Center Murray Utah
United States Vanderbilt University Medical Center Nashville Tennessee
United States Yale School of Medicine Digestive Diseases, Internal Medicine New Haven Connecticut
United States Tulane University School of Medicine New Orleans Louisiana
United States Center for Liver Disease and Transplantation New York New York
United States Concorde Medical Group New York New York
United States Icahn School of Medicine at Mount Sinai New York New York
United States NYU Langone Health New York New York
United States Mary Immaculate Hospital Newport News Virginia
United States Henry Ford Health System Novi Michigan
United States Mayo Clinic Arizona - PPDS Phoenix Arizona
United States University of Pittsburgh Medical Center Pittsburgh Pennsylvania
United States Stanford University School of Medicine Redwood City California
United States Bon Secours Richmond Community Hospital Richmond Virginia
United States University of Rochester Medical Center Rochester New York
United States University of California Davis Medical Center Sacramento California
United States American Research Corporation at Texas Liver Institute San Antonio Texas
United States Pinnacle Clinical Research San Antonio Texas
United States California Pacific Medical Center San Francisco California
United States Swedish Medical Center Seattle Washington
United States Tampa General Medical Group Tampa Florida
United States The Institute for Liver Health-Tucson Tucson Arizona
United States Digestive Health Specialists PA Tupelo Mississippi

Sponsors (1)

Lead Sponsor Collaborator
CymaBay Therapeutics, Inc.

Countries where clinical trial is conducted

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

Outcome

Type Measure Description Time frame Safety issue
Primary Percentage of Participants With Response to Composite Endpoint of ALP <1.67 × Upper Limit of Normal [ULN], =15% Reduction in ALP, and Total Bilirubin = ULN) at Month 3 Percentage of Participants with Response to Composite Endpoint of ALP <1.67 × Upper Limit of Normal [ULN], =15% reduction in ALP, and total bilirubin = ULN) at Month 3. The mITT analysis set included all randomized subjects who received at least one study drug dose.
The primary endpoint was analyzed using Cochran-Mantel-Haenszel (CMH) test adjusted for both randomization stratification variables (ALP level: <350 U/L and 2:350 U/L; pruritus NRS: <4 and 2:4). The CMH tests were performed for the comparison of 10 mg versus placebo and 5 mg/10 mg versus placebo separately.
Month 3
Secondary Percentage of Participants With Response Defined by Normalized Alkaline Phosphatase Levels at Month 3 The response was defined by normalized ALP levels (ALP =1.0 × ULN) at endpoint. The mITT analysis set included all randomized subjects who received at least one study drug dose. Month 3
Secondary Change From Baseline in Pruritus NRS for Subjects With Baseline NRS =4 at Month 3 Pruritus Numerical Rating Scale (NRS) used to rate the intensity of the worst itching you experienced in the past 24 hours from no itching to worst possible itching by selecting a number from 0 to 10 on Itch Scale. Zero means no itching and 10 means worst imaginable itching. The analysis will be limited to those subjects in the mITT analysis set with a baseline NRS = 4. Month 3
See also
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