ENHANCE: Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and an Inadequate Response to or an Intolerance to Ursodeoxycholic Acid (UDCA)

NCT03602560 | Completed Phase 3 Results FDA Drug

• 1 other identifier: CB8025-31735
• Study Type: interventional
• Target: 265
• Locations: 22 countries
• Sites: 151

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.

Conditions

Primary Biliary Cholangitis

Keywords

PBC; Primary Biliary Cholangitis (PBC)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Percentage of Participants With Response Defined by Normalized Alkaline Phosphatase Levels at Month 3

  Month 3

• Change From Baseline in Pruritus NRS for Subjects With Baseline NRS ≥4 at Month 3

  Month 3

Study Arms (3)

Seladelpar 5-10 mg

EXPERIMENTAL

Drug: seladelpar 5-10 mg

Seladelpar 10 mg

EXPERIMENTAL

Drug: seladelpar 10 mg

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

seladelpar 5-10 mg DRUG

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 5-10 mg

seladelpar 10 mg DRUG

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

Seladelpar 10 mg

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have given written informed consent (signed and dated) and any authorizations required by local law
• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (156)

Institute for Liver Health

Chandler, Arizona, 85224, United States

Location

Mayo Clinic Arizona - PPDS

Phoenix, Arizona, 85054, United States

Location

The Institute for Liver Health-Tucson

Tucson, Arizona, 85711, United States

Location

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Stanford University School of Medicine

Redwood City, California, 94063, United States

Location

University of California Davis Medical Center

Sacramento, California, 95817, United States

Location

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

Univeristy of Colorado Denver and Hospital

Aurora, Colorado, 80045, United States

Location

Yale School of Medicine Digestive Diseases, Internal Medicine

New Haven, Connecticut, 06510, United States

Location

Excel Medical Clinical Trials, LLC

Boca Raton, Florida, 33434, United States

Location

Florida Reserach Institute

Lakewood Rch, Florida, 34211, United States

Location

Schiff Center for Liver Diseases University of Miami

Miami, Florida, 33136, United States

Location

Tampa General Medical Group

Tampa, Florida, 33606, United States

Location

Digestive Healthcare of Georgia

Atlanta, Georgia, 30309, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Indianapolis Gastroenterology Research Foundation

Indianapolis, Indiana, 46237, United States

Location

University of Kansas Hospital

Kansas City, Kansas, 66160, United States

Location

Tulane University School of Medicine

New Orleans, Louisiana, 70112, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02114, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Henry Ford Health System

Novi, Michigan, 48377, United States

Location

Minnesota Gastroenterlogy, P.A.

Maplewood, Minnesota, 55117, United States

Location

University of Minnesota Medical Center, Fairview

Minneapolis, Minnesota, 55455, United States

Location

Southern Therapy and Advance Research (STAR) LLC

Jackson, Mississippi, 39216, United States

Location

Digestive Health Specialists PA

Tupelo, Mississippi, 38801, United States

Location

Kansas City Research Institute

Kansas City, Missouri, 64131, United States

Location

Concorde Medical Group

New York, New York, 10016, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Center for Liver Disease and Transplantation

New York, New York, 10032, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Asheville Gastroenterology Associates, a Division of Digestive Health Partners, P.A.

Asheville, North Carolina, 28801, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

UH Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Northeast Clinical Research Center, LLC

Bethlehem, Pennsylvania, 18017, United States

Location

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Gastro One

Germantown, Tennessee, 38138, United States

Location

GIA Clinical Trials, LLC

Knoxville, Tennessee, 37909, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Liver Institute at Methodist Dallas

Dallas, Texas, 75203, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Texas Digestive Disease Consultants

Fort Worth, Texas, 76104, United States

Location

American Research Corporation

Houston, Texas, 77030, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

American Research Corporation at Texas Liver Institute

San Antonio, Texas, 78215, United States

Location

Pinnacle Clinical Research

San Antonio, Texas, 78229, United States

Location

Intermountain Medical Center

Murray, Utah, 84107, United States

Location

Mary Immaculate Hospital

Newport News, Virginia, 23602, United States

Location

Bon Secours Richmond Community Hospital

Richmond, Virginia, 23226, United States

Location

Swedish Medical Center

Seattle, Washington, 98104, United States

Location

Hospital Universitario Austral

Pilar, Buenos Aires, B1629AHJ, Argentina

Location

Fundación Sanatorio Güemes

Buenos Aires, Ciudad Autónoma de BuenosAires, C1180AAX, Argentina

Location

Hospital Provincial Del Centenario

Rosario, Santa Fe Province, S2000KDS, Argentina

Location

DIM Clínica Privada

Ramos Mejía, B1704ETD, Argentina

Location

The Canberra Hospital

Garran, Australian Capital Territory, 2605, Australia

Location

Royal Brisbane & Women's Hospital

Herston, Queensland, 4029, Australia

Location

St Vincents Hospital Melbourne

Fitzroy, Victoria, 3065, Australia

Location

Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

Location

Medizinische Universitat Wien

Vienna, Vienna, A-1090, Austria

Location

LKH-Universitätsklinikum Klinikum Graz

Graz, 8036, Austria

Location

Salzburger Landeskliniken

Salzburg, 5020, Austria

Location

Klinikum Wels-Grieskirchen GmbH

Wels, 4600, Austria

Location

UZ Antwerpen

Edegem, Antwerpen, 2650, Belgium

Location

UZ Gent

Ghent, Oost-Vlaanderen, 9000, Belgium

Location

UZ Leuven

Leuven, Vlaams Brabant, 3000, Belgium

Location

University of Calgary Medicine

Calgary, Alberta, T2N 4Z6, Canada

Location

University of Manitoba

Winnipeg, Manitoba, R3E 3P4, Canada

Location

University Health Network

Toronto, Ontario, M5G 2C4, Canada

Location

Toronto Digestive Disease Associates Inc

Vaughan, Ontario, M3N 2V7, Canada

Location

McGill University Health Centre (MUHC)

Montreal, Quebec, H4A 3J1, Canada

Location

Pontificia Universidad Catolica de Chile

Santiago, Región-MetropolitanadeSantiago, 8330034, Chile

Location

Centro Clinico Mediterraneo

La Serena, 1720506, Chile

Location

Centro de Investigaciones Clínicas Vina del Mar

Viña del Mar, 2540364, Chile

Location

Hôpital Jean Verdier

Bondy, 93140, France

Location

CHU de GRENOBLE

Grenoble, 38043, France

Location

Hôpital Saint Antoine

Paris, 75012, France

Location

Universitätsklinikum Tübingen

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Uniklinik Köln

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Gastroenterologische Gemeinschaftspraxis Herne

Herne, North Rhine-Westphalia, 44623, Germany

Location

Gastroenterologisch Hepatologisches Zentrum Kiel

Kiel, Schleswig-Holstein, 24146, Germany

Location

Charité - Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

Universitätsklinikum Erlangen

Erlangen, 91054, Germany

Location

ifi-Institute for Interdisciplinary Medicine

Hamburg, 20246, Germany

Location

Universitatsklinikum Leipzig

Leipzig, 04103, Germany

Location

University General Hospital of Heraklion

Heraklion, 71110, Greece

Location

University General Hospital of Larissa

Larissa, 41110, Greece

Location

University General Hospital of Patras

Pátrai, 26504, Greece

Location

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont

Szeged, Csongrád megye, 6720, Hungary

Location

Budai Hepatológiai Centrum

Budapest, 1111, Hungary

Location

Debreceni Egyetem Klinikai Kozpont

Debrecen, 4032, Hungary

Location

Somogy Megyei Kaposi Mór Oktató Kórház

Kaposvár, 7400, Hungary

Location

Hillel Yaffe Medical Center

Hadera, 38100, Israel

Location

Carmel Medical Center

Haifa, 31048, Israel

Location

Rambam Health Corporation

Haifa, 31096, Israel

Location

Hadassah Medical Center

Jerusalem, 91120, Israel

Location

The Galilli Medical Center

Nahariya, 22100, Israel

Location

Chaim Sheba Medical Center

Ramat Gan, 52662, Israel

Location

Kaplan Medical Center

Rehovot, 76100, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

Azienda Ospedaliera Universitaria Careggi

Florence, 50134, Italy

Location

ASST Santi Paolo e Carlo - Azienda Universitaria-Polo Universitario San Paolo

Milan, 20142, Italy

Location

Ospedale Civile di Baggiovara

Modena, 41126, Italy

Location

Azienda Ospedaliera Di Padova

Padua, 35128, Italy

Location

ASST di Monza - Azienda Ospedaliera San Gerardo

Rozzano, 20090, Italy

Location

Centro de Diabetes y Obesidad Graber

Pachuca, Hidalgo, 42086, Mexico

Location

Consultorio de la Doctora Maria Sarai Gonzalez Huezo

Metepec, 52140, Mexico

Location

Consultorio Medico - Distrito Federal

Mexico City, 06700, Mexico

Location

Radboud Universitair Medisch Centrum

Nijmegen, Gelderland, 6525 GA, Netherlands

Location

Christchurch Hospital

Christchurch, South Island, 8011, New Zealand

Location

Dunedin Hospital

Dunedin, South Island, 9001, New Zealand

Location

Waikato Hospital

Hamilton, 3240, New Zealand

Location

Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza w Bydgoszczy

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-030, Poland

Location

Centrum Onkologii Instytut im. Marii Sklodowskiej-Curie

Warsaw, Masovian Voivodeship, 02-781, Poland

Location

Samodzielny Publiczny Szpital Kliniczny Nr 7 Slaskiego Uniwersytetu Medycznego w Katowicach

Katowice, Silesian Voivodeship, 40-752, Poland

Location

Wojewodzki Szpital Zespolony w Kielcach

Kielce, 25-317, Poland

Location

SP ZOZ Szpital Uniwersytecki w Krakowie

Krakow, 31-531, Poland

Location

ID Clinic

Mysłowice, 41-400, Poland

Location

Pius Brinzeu Emergency Clinical County Hospital

Timișoara, Timiș County, 300723, Romania

Location

Colentina Clinical Hospital

Bucharest, 020125, Romania

Location

Fundeni Clinical Institute

Bucharest, 022328, Romania

Location

Sana Monitoring SRL

Bucharest, Romania

Location

Peoples Friendship University of Russia

Moscow, Moscow, 117198, Russia

Location

City Hospital #31

Saint Petersburg, 197110, Russia

Location

Ulyanovsk Regional Clinical Hospital

Ulyanovsk, 432063, Russia

Location

Clinical Hospital Centar Zvezdara

Belgrade, 11000, Serbia

Location

KBC Zemun

Belgrade, 11080, Serbia

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggido, 13620, South Korea

Location

Pusan National University Hospital

Busan, 49241, South Korea

Location

Kyungpook National University Hospital

Daegu, 700-721, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Inje University Ilsan Paik Hospital

Seoul, 03722, South Korea

Location

Gangnam Severance Hospital, Yonsei University Health System

Seoul, 06273, South Korea

Location

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, 137 701, South Korea

Location

Severance Hospital Yonsei University Health System

Seoul, South Korea

Location

Hospital Universitario Puerta de Hierro - Majadahonda

Majadahonda, Madrid, 28222, Spain

Location

Hospital Universitario Vall d'Hebrón - PPDS

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario Germans Trias i Pujol

Barcelona, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, 46026, Spain

Location

Queen Alexandra Hospital

Portsmouth, Hampshire, PO6 3LY, United Kingdom

Location

University Hospital Birmingham

Birmingham, B15 2TT, United Kingdom

Location

Hull and East Yorkshire Hospitals NHS Trust

Hull, HU3 2JZ, United Kingdom

Location

Barts Health NHS Trust, Royal London Hospital, Ambrose King Centre

London, E1 1BB, United Kingdom

Location

Royal Free London NHS Foundation Trust

London, NW3 2QG, United Kingdom

Location

Kings College Hospital

London, SE5 9RS, United Kingdom

Location

The Newcastle Upon Tyne Hospital NHS Foundation Trust

Newcastle, NE7 7DN, United Kingdom

Location

University of Nottingham

Nottingham, NG7 2UH, United Kingdom

Location

Plymouth Hospitals NHS Trust

Plymouth, PL6 8DH, United Kingdom

Location

Singleton Hospital

Swansea, SA2 8QA, United Kingdom

Location

MeSH Terms

Conditions

Liver Cirrhosis, Biliary

Interventions

seladelpar

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Elaine Watkins, DO, MSPH, Vice President of Clinical Development
• Organization: CymaBay Therapeutics, Inc.

medinfo@cymabay.com

510-293-8800

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2018
• First Posted: July 27, 2018
• Study Start: October 1, 2018
• Primary Completion: February 16, 2020
• Study Completion: February 16, 2020
• Last Updated: August 2, 2022
• Results First Posted: May 31, 2022

Record last verified: 2022-07

Locations

IT (5); PL (6); IL (8); ES (10); SE (2); HU (4); BE (3); FR (3); GR (3); GB (10); NL (1); DE (8); RU (3); KR (8); AU (4); CL (3); ME (3); NZ (3); RO (4); US (51); AR (4); CA (5)