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

NCT ID: NCT03602560

Last Updated: 2022-08-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 265 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-01
• Study Completion Date: 2020-02-16

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

Conditions

Primary Biliary Cholangitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Seladelpar 5-10 mg

Group Type: EXPERIMENTAL

seladelpar 5-10 mg

Intervention Type: 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 10 mg

Group Type: EXPERIMENTAL

seladelpar 10 mg

Intervention Type: 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

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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

Interventions

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Institute for Liver Health

Chandler, Arizona, United States

Mayo Clinic Arizona - PPDS

Phoenix, Arizona, United States

The Institute for Liver Health-Tucson

Tucson, Arizona, United States

Cedars Sinai Medical Center

Los Angeles, California, United States

Stanford University School of Medicine

Redwood City, California, 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

Excel Medical Clinical Trials, LLC

Boca Raton, Florida, United States

Florida Reserach Institute

Lakewood Rch, Florida, United States

Schiff Center for Liver Diseases University of Miami

Miami, Florida, United States

Tampa General Medical Group

Tampa, Florida, United States

Digestive Healthcare of Georgia

Atlanta, Georgia, United States

University of Chicago Medical Center

Chicago, Illinois, 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

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Henry Ford Health System

Novi, Michigan, United States

Minnesota Gastroenterlogy, P.A.

Maplewood, Minnesota, United States

University of Minnesota Medical Center, Fairview

Minneapolis, Minnesota, United States

Southern Therapy and Advance Research (STAR) LLC

Jackson, Mississippi, United States

Digestive Health Specialists PA

Tupelo, Mississippi, United States

Kansas City Research Institute

Kansas City, Missouri, United States

Concorde Medical Group

New York, New York, United States

NYU Langone Health

New York, New York, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Center for Liver Disease and Transplantation

New York, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

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

Asheville, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

UH Cleveland Medical Center

Cleveland, Ohio, United States

Northeast Clinical Research Center, LLC

Bethlehem, Pennsylvania, United States

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Gastro One

Germantown, Tennessee, United States

GIA Clinical Trials, LLC

Knoxville, Tennessee, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Liver Institute at Methodist Dallas

Dallas, Texas, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Texas Digestive Disease Consultants

Fort Worth, Texas, United States

American Research Corporation

Houston, Texas, United States

Baylor College of Medicine

Houston, Texas, United States

American Research Corporation at Texas Liver Institute

San Antonio, Texas, United States

Pinnacle Clinical Research

San Antonio, Texas, United States

Intermountain Medical Center

Murray, Utah, United States

Mary Immaculate Hospital

Newport News, Virginia, United States

Bon Secours Richmond Community Hospital

Richmond, Virginia, United States

Swedish Medical Center

Seattle, Washington, United States

Hospital Universitario Austral

Pilar, Buenos Aires, Argentina

Fundación Sanatorio Güemes

Buenos Aires, Ciudad Autónoma de BuenosAires, Argentina

Hospital Provincial Del Centenario

Rosario, Santa Fe Province, Argentina

DIM Clínica Privada

Ramos Mejía, , Argentina

The Canberra Hospital

Garran, Australian Capital Territory, Australia

Royal Brisbane & Women's Hospital

Herston, Queensland, Australia

St Vincents Hospital Melbourne

Fitzroy, Victoria, Australia

Royal Melbourne Hospital

Parkville, Victoria, Australia

Royal Perth Hospital

Perth, Western Australia, Australia

Medizinische Universitat Wien

Vienna, Vienna, Austria

LKH-Universitätsklinikum Klinikum Graz

Graz, , Austria

Salzburger Landeskliniken

Salzburg, , Austria

Klinikum Wels-Grieskirchen GmbH

Wels, , Austria

UZ Antwerpen

Edegem, Antwerpen, Belgium

UZ Gent

Ghent, Oost-Vlaanderen, Belgium

UZ Leuven

Leuven, Vlaams Brabant, Belgium

University of Calgary Medicine

Calgary, Alberta, Canada

University of Manitoba

Winnipeg, Manitoba, Canada

University Health Network

Toronto, Ontario, Canada

Toronto Digestive Disease Associates Inc

Vaughan, Ontario, Canada

McGill University Health Centre (MUHC)

Montreal, Quebec, Canada

Pontificia Universidad Catolica de Chile

Santiago, Región-MetropolitanadeSantiago, Chile

Centro Clinico Mediterraneo

La Serena, , Chile

Centro de Investigaciones Clínicas Vina del Mar

Viña del Mar, , Chile

Hôpital Jean Verdier

Bondy, , France

CHU de GRENOBLE

Grenoble, , France

Hôpital Saint Antoine

Paris, , France

Universitätsklinikum Tübingen

Tübingen, Baden-Wurttemberg, Germany

Uniklinik Köln

Cologne, North Rhine-Westphalia, Germany

Gastroenterologische Gemeinschaftspraxis Herne

Herne, North Rhine-Westphalia, Germany

Gastroenterologisch Hepatologisches Zentrum Kiel

Kiel, Schleswig-Holstein, Germany

Charité - Universitätsmedizin Berlin

Berlin, , Germany

Universitätsklinikum Erlangen

Erlangen, , Germany

ifi-Institute for Interdisciplinary Medicine

Hamburg, , Germany

Universitatsklinikum Leipzig

Leipzig, , Germany

University General Hospital of Heraklion

Heraklion, , Greece

University General Hospital of Larissa

Larissa, , Greece

University General Hospital of Patras

Pátrai, , Greece

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont

Szeged, Csongrád megye, Hungary

Budai Hepatológiai Centrum

Budapest, , Hungary

Debreceni Egyetem Klinikai Kozpont

Debrecen, , Hungary

Somogy Megyei Kaposi Mór Oktató Kórház

Kaposvár, , Hungary

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

Rehovot, , Israel

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Azienda Ospedaliera Universitaria Careggi

Florence, , Italy

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

Milan, , Italy

Ospedale Civile di Baggiovara

Modena, , Italy

Azienda Ospedaliera Di Padova

Padua, , Italy

ASST di Monza - Azienda Ospedaliera San Gerardo

Rozzano, , Italy

Centro de Diabetes y Obesidad Graber

Pachuca, Hidalgo, Mexico

Consultorio de la Doctora Maria Sarai Gonzalez Huezo

Metepec, , Mexico

Consultorio Medico - Distrito Federal

Mexico City, , Mexico

Radboud Universitair Medisch Centrum

Nijmegen, Gelderland, Netherlands

Christchurch Hospital

Christchurch, South Island, New Zealand

Dunedin Hospital

Dunedin, South Island, New Zealand

Waikato Hospital

Hamilton, , New Zealand

Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza w Bydgoszczy

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland

Centrum Onkologii Instytut im. Marii Sklodowskiej-Curie

Warsaw, Masovian Voivodeship, Poland

Samodzielny Publiczny Szpital Kliniczny Nr 7 Slaskiego Uniwersytetu Medycznego w Katowicach

Katowice, Silesian Voivodeship, Poland

Wojewodzki Szpital Zespolony w Kielcach

Kielce, , Poland

SP ZOZ Szpital Uniwersytecki w Krakowie

Krakow, , Poland

ID Clinic

Mysłowice, , Poland

Pius Brinzeu Emergency Clinical County Hospital

Timișoara, Timiș County, Romania

Colentina Clinical Hospital

Bucharest, , Romania

Fundeni Clinical Institute

Bucharest, , Romania

Sana Monitoring SRL

Bucharest, , Romania

Peoples Friendship University of Russia

Moscow, Moscow, Russia

City Hospital #31

Saint Petersburg, , Russia

Ulyanovsk Regional Clinical Hospital

Ulyanovsk, , Russia

Clinical Hospital Centar Zvezdara

Belgrade, , Serbia

KBC Zemun

Belgrade, , Serbia

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggido, South Korea

Pusan National University Hospital

Busan, , South Korea

Kyungpook National University Hospital

Daegu, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Inje University Ilsan Paik Hospital

Seoul, , South Korea

Gangnam Severance Hospital, Yonsei University Health System

Seoul, , South Korea

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

Seoul, , South Korea

Severance Hospital Yonsei University Health System

Seoul, , South Korea

Hospital Universitario Puerta de Hierro - Majadahonda

Majadahonda, Madrid, Spain

Hospital Universitario Vall d'Hebrón - PPDS

Barcelona, , Spain

Hospital Clinic de Barcelona

Barcelona, , Spain

Hospital Universitario Germans Trias i Pujol

Barcelona, , Spain

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Universitario Virgen de la Victoria

Málaga, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, , Spain

Queen Alexandra Hospital

Portsmouth, Hampshire, 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

Royal Free London NHS Foundation Trust

London, , United Kingdom

Kings College Hospital

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

Singleton Hospital

Swansea, , United Kingdom

Countries

United States; Argentina; Australia; Austria; Belgium; Canada; Chile; France; Germany; Greece; Hungary; Israel; Italy; Mexico; Netherlands; New Zealand; Poland; Romania; Russia; Serbia; South Korea; Spain; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CB8025-31735

Identifier Type: -

Identifier Source: org_study_id