Primary Biliary Cholangitis Clinical Trial
Official title:
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 an Intolerance to Ursodeoxycholic Acid (UDCA)
Verified date | July 2022 |
Source | CymaBay Therapeutics, Inc. |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
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 |
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 |
Lead Sponsor | Collaborator |
---|---|
CymaBay Therapeutics, Inc. |
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,
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 |
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