ENHANCE: Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and an Inadequate Response to or an Intolerance to Ursodeoxycholic Acid (UDCA)
- Conditions
- Primary Biliary Cholangitis
- Interventions
- Registration Number
- NCT03602560
- Lead Sponsor
- CymaBay Therapeutics, Inc.
- Brief 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.
- Detailed 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 & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 265
-
Must have given written informed consent (signed and dated) and any authorizations required by local law
-
18 to 75 years old (inclusive)
-
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
-
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)
-
AP ≥ 1.67 × ULN
-
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
-
Previous exposure to seladelpar (MBX-8025)
-
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)
-
AST above 3 × ULN
-
ALT above 3 × ULN
-
Total bilirubin above 2.0 × ULN
-
Advanced PBC as defined by the Rotterdam criteria (albumin below LLN AND total bilirubin above 1 × ULN)
-
Creatine kinase (CK) above 1.0 × ULN
-
eGFR below 60 mL/min/1.73 m2 (calculated by MDRD formula)
-
International normalized ratio (INR) above 1.0 × ULN
-
Platelet count below 100 × 103/µL
-
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
-
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
-
Known history of HIV
-
Evidence of significant alcohol consumption
-
Evidence of drug abuse
-
Subjects with inadequate response to obeticholic acid (OCA) or intolerance to OCA: OCA must be discontinued 30 days prior to Screening
-
Use of colchicine, methotrexate, azathioprine, or long-term systemic corticosteroids (> 2 weeks) within two months prior to Screening
-
Use of fibrates within 30 days prior to Screening
-
Use of simvastatin within 7 days prior to Screening
-
Use of an experimental or unapproved treatment for PBC within 30 days prior to Screening
-
Use of experimental or unapproved immunosuppressant within 30 days prior to Screening
-
Treatment with any other investigational therapy or device within 30 days or within five half-lives, whatever is longer, prior to Screening
-
For females, pregnancy or breast-feeding
-
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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Seladelpar 5-10 mg seladelpar 5-10 mg - Seladelpar 10 mg seladelpar 10 mg - Placebo Placebo -
- Primary Outcome Measures
Name Time Method 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 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.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Pruritus NRS for Subjects With Baseline NRS ≥4 at Month 3 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.
Percentage of Participants With Response Defined by Normalized Alkaline Phosphatase Levels at Month 3 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.
Trial Locations
- Locations (156)
Henry Ford Health System
🇺🇸Novi, Michigan, United States
Liver Institute at Methodist Dallas
🇺🇸Dallas, Texas, United States
Cedars Sinai Medical Center
🇺🇸Los Angeles, California, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
UH Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Schiff Center for Liver Diseases University of Miami
🇺🇸Miami, Florida, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
American Research Corporation
🇺🇸Houston, Texas, United States
Wojewodzki Szpital Zespolony w Kielcach
🇵🇱Kielce, Poland
UZ Antwerpen
🇧🇪Edegem, Antwerpen, Belgium
UZ Leuven
🇧🇪Leuven, Vlaams Brabant, Belgium
Gastroenterologisch Hepatologisches Zentrum Kiel
🇩🇪Kiel, Schleswig-Holstein, Germany
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Sana Monitoring SRL
🇷🇴Bucharest, Romania
Clinical Hospital Centar Zvezdara
🇷🇸Belgrade, Serbia
Hospital Provincial Del Centenario
🇦🇷Rosario, Santa Fe, Argentina
Queen Alexandra Hospital
🇬🇧Portsmouth, Hampshire, United Kingdom
Universitätsklinikum Tübingen
🇩🇪Tübingen, Baden-Württemberg, Germany
Klinikum Wels-Grieskirchen GmbH
🇦🇹Wels, Austria
Pontificia Universidad Catolica de Chile
🇨🇱Santiago, Región-MetropolitanadeSantiago, Chile
Consultorio Medico - Distrito Federal
🇲🇽Ciudad de Mexico, Mexico
Salzburger Landeskliniken
🇦🇹Salzburg, Austria
Centro Clinico Mediterraneo
🇨🇱La Serena, Chile
Pius Brinzeu Emergency Clinical County Hospital
🇷🇴Timişoara, Timis, Romania
Radboud Universitair Medisch Centrum
🇳🇱Nijmegen, Gelderland, Netherlands
University Health Network
🇨🇦Toronto, Ontario, Canada
Singleton Hospital
🇬🇧Swansea, United Kingdom
Institute for Liver Health
🇺🇸Chandler, Arizona, United States
The Institute for Liver Health-Tucson
🇺🇸Tucson, Arizona, United States
Stanford University School of Medicine
🇺🇸Redwood City, California, United States
Southern Therapy and Advance Research (STAR) LLC
🇺🇸Jackson, Mississippi, United States
Asheville Gastroenterology Associates, a Division of Digestive Health Partners, P.A.
🇺🇸Asheville, North Carolina, United States
Fundación Sanatorio Güemes
🇦🇷Buenos Aires, Ciudad Autónoma De BuenosAires, Argentina
Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
The Canberra Hospital
🇦🇺Garran, Australian Capital Territory, Australia
Medizinische Universitat Wien
🇦🇹Vienna, Wien, Austria
St Vincents Hospital Melbourne
🇦🇺Fitzroy, Victoria, Australia
Centro de Investigaciones Clínicas Vina del Mar
🇨🇱Viña Del Mar, Chile
University of Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Rambam Health Corporation
🇮🇱Haifa, Israel
Azienda Ospedaliera Universitaria Careggi
🇮🇹Firenze, Italy
Consultorio de la Doctora Maria Sarai Gonzalez Huezo
🇲🇽Metepec, Mexico
Centro de Diabetes y Obesidad Graber
🇲🇽Pachuca de Soto, Hidalgo, Mexico
Samodzielny Publiczny Szpital Kliniczny Nr 7 Slaskiego Uniwersytetu Medycznego w Katowicach
🇵🇱Katowice, Slaskie, Poland
ID Clinic
🇵🇱Mysłowice, Poland
Fundeni Clinical Institute
🇷🇴Bucharest, Romania
Peoples Friendship University of Russia
🇷🇺Moscow, Moskva, Russian Federation
Hospital Universitario Germans Trias i Pujol
🇪🇸Barcelona, Spain
Hospital Universitario Puerta de Hierro - Majadahonda
🇪🇸Majadahonda, Madrid, Spain
Kings College Hospital
🇬🇧London, United Kingdom
The Newcastle Upon Tyne Hospital NHS Foundation Trust
🇬🇧Newcastle, United Kingdom
Plymouth Hospitals NHS Trust
🇬🇧Plymouth, United Kingdom
Hôpital Jean Verdier
🇫🇷Bondy, France
Kyungpook National University Hospital
🇰🇷Daegu, Korea, Republic of
Inje University Ilsan Paik Hospital
🇰🇷Seoul, Korea, Republic of
Ulyanovsk Regional Clinical Hospital
🇷🇺Ulyanovsk, Russian Federation
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Gastroenterologische Gemeinschaftspraxis Herne
🇩🇪Herne, Nordrhein-Westfalen, Germany
The Galilli Medical Center
🇮🇱Nahariya, Israel
Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
Kaplan Medical Center
🇮🇱Reẖovot, Israel
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
🇭🇺Szeged, Csongrád, Hungary
Christchurch Hospital
🇳🇿Christchurch, South Island, New Zealand
Florida Reserach Institute
🇺🇸Lakewood Ranch, Florida, United States
Excel Medical Clinical Trials, LLC
🇺🇸Boca Raton, Florida, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Digestive Healthcare of Georgia
🇺🇸Atlanta, Georgia, United States
Indianapolis Gastroenterology Research Foundation
🇺🇸Indianapolis, Indiana, United States
University of Kansas Hospital
🇺🇸Kansas City, Kansas, United States
Tulane University School of Medicine
🇺🇸New Orleans, Louisiana, United States
Minnesota Gastroenterlogy, P.A.
🇺🇸Maplewood, Minnesota, United States
Concorde Medical Group
🇺🇸New York, New York, United States
NYU Langone Health
🇺🇸New York, New York, United States
Center for Liver Disease and Transplantation
🇺🇸New York, New York, United States
Penn State Milton S Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Northeast Clinical Research Center, LLC
🇺🇸Bethlehem, Pennsylvania, United States
Gastro One
🇺🇸Germantown, Tennessee, United States
GIA Clinical Trials, LLC
🇺🇸Knoxville, Tennessee, United States
Texas Digestive Disease Consultants
🇺🇸Fort Worth, Texas, United States
Intermountain Medical Center
🇺🇸Murray, Utah, United States
Swedish Medical Center
🇺🇸Seattle, Washington, United States
Mary Immaculate Hospital
🇺🇸Newport News, Virginia, United States
Hospital Universitario Austral
🇦🇷Pilar, Buenos Aires, Argentina
Bon Secours Richmond Community Hospital
🇺🇸Richmond, Virginia, United States
DIM Clínica Privada
🇦🇷Ramos Mejía, Argentina
Royal Brisbane & Women's Hospital
🇦🇺Herston, Queensland, Australia
Royal Perth Hospital
🇦🇺Perth, Western Australia, Australia
LKH-Universitätsklinikum Klinikum Graz
🇦🇹Graz, Austria
UZ Gent
🇧🇪Gent, Oost-Vlaanderen, Belgium
McGill University Health Centre (MUHC)
🇨🇦Montréal, Quebec, Canada
University of Calgary Medicine
🇨🇦Calgary, Alberta, Canada
CHU de GRENOBLE
🇫🇷Grenoble, France
Hôpital Saint Antoine
🇫🇷Paris, France
Uniklinik Köln
🇩🇪Köln, Nordrhein-Westfalen, Germany
ifi-Institute for Interdisciplinary Medicine
🇩🇪Hamburg, Germany
Charité - Universitätsmedizin Berlin
🇩🇪Berlin, Germany
Universitätsklinikum Erlangen
🇩🇪Erlangen, Germany
Universitatsklinikum Leipzig
🇩🇪Leipzig, Germany
University General Hospital of Heraklion
🇬🇷Heraklion, Greece
University General Hospital of Larissa
🇬🇷Larissa, Greece
University General Hospital of Patras
🇬🇷Patras, Greece
Debreceni Egyetem Klinikai Kozpont
🇭🇺Debrecen, Hungary
Somogy Megyei Kaposi Mór Oktató Kórház
🇭🇺Kaposvár, Hungary
Budai Hepatológiai Centrum
🇭🇺Budapest, Hungary
Hillel Yaffe Medical Center
🇮🇱Hadera, Israel
Carmel Medical Center
🇮🇱Haifa, Israel
Hadassah Medical Center
🇮🇱Jerusalem, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
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, Italy
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Severance Hospital Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Dunedin Hospital
🇳🇿Dunedin, South Island, New Zealand
Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza w Bydgoszczy
🇵🇱Bydgoszcz, Kujawsko-pomorskie, Poland
Centrum Onkologii Instytut im. Marii Sklodowskiej-Curie
🇵🇱Warszawa, Mazowieckie, Poland
SP ZOZ Szpital Uniwersytecki w Krakowie
🇵🇱Kraków, Poland
Colentina Clinical Hospital
🇷🇴Bucharest, Romania
City Hospital #31
🇷🇺St. Petersburg, Russian Federation
KBC Zemun
🇷🇸Belgrade, Serbia
Hospital Universitario Vall d'Hebrón - PPDS
🇪🇸Barcelona, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital Universitario Virgen de la Victoria
🇪🇸Málaga, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Hospital Universitari i Politecnic La Fe de Valencia
🇪🇸Valencia, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
University Hospital Birmingham
🇬🇧Birmingham, United Kingdom
Barts Health NHS Trust, Royal London Hospital, Ambrose King Centre
🇬🇧London, United Kingdom
Hull and East Yorkshire Hospitals NHS Trust
🇬🇧Hull, United Kingdom
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
The Catholic University of Korea, Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Digestive Health Specialists PA
🇺🇸Tupelo, Mississippi, United States
Waikato Hospital
🇳🇿Hamilton, New Zealand
Toronto Digestive Disease Associates Inc
🇨🇦Vaughan, Ontario, Canada
Gangnam Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Gyeonggido, Korea, Republic of
Mayo Clinic Arizona - PPDS
🇺🇸Phoenix, Arizona, United States
University of California Davis Medical Center
🇺🇸Sacramento, California, United States
California Pacific Medical Center
🇺🇸San Francisco, California, United States
Univeristy of Colorado Denver and Hospital
🇺🇸Aurora, Colorado, United States
Yale School of Medicine Digestive Diseases, Internal Medicine
🇺🇸New Haven, Connecticut, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Tampa General Medical Group
🇺🇸Tampa, Florida, United States
University of Minnesota Medical Center, Fairview
🇺🇸Minneapolis, Minnesota, United States
American Research Corporation at Texas Liver Institute
🇺🇸San Antonio, Texas, United States
Pinnacle Clinical Research
🇺🇸San Antonio, Texas, United States
Kansas City Research Institute
🇺🇸Kansas City, Missouri, United States
Royal Free London NHS Foundation Trust
🇬🇧London, United Kingdom
University of Nottingham
🇬🇧Nottingham, United Kingdom