Clinical trial NCT03602560: ENHANCE: Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and an Inadequate Response to or an Intolerance to Ursodeoxycholic Acid (UDCA)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Biliary Cholangitis
Keywords: PBC
Primary Biliary Cholangitis (PBC)
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2018-07-27
Enrollment: 265
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: 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
timeFrame: Month 3
Secondary outcomes:
measure: Percentage of Participants With Response Defined by Normalized Alkaline Phosphatase Levels at Month 3
timeFrame: Month 3
measure: Change From Baseline in Pruritus NRS for Subjects With Baseline NRS ≥4 at Month 3
timeFrame: Month 3
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Institute for Liver Health
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic Arizona - PPDS
state: Arizona
city: Tucson
country: United States
facility: The Institute for Liver Health-Tucson
state: Arizona
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Redwood City
country: United States
facility: Stanford University School of Medicine
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Aurora
country: United States
facility: Univeristy of Colorado Denver and Hospital
state: Colorado
city: New Haven
country: United States
facility: Yale School of Medicine Digestive Diseases, Internal Medicine
state: Connecticut
city: Boca Raton
country: United States
facility: Excel Medical Clinical Trials, LLC
state: Florida
city: Lakewood Ranch
country: United States
facility: Florida Reserach Institute
state: Florida
city: Miami
country: United States
facility: Schiff Center for Liver Diseases University of Miami
state: Florida
city: Tampa
country: United States
facility: Tampa General Medical Group
state: Florida
city: Atlanta
country: United States
facility: Digestive Healthcare of Georgia
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indianapolis Gastroenterology Research Foundation
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Hospital
state: Kansas
city: New Orleans
country: United States
facility: Tulane University School of Medicine
state: Louisiana
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Novi
country: United States
facility: Henry Ford Health System
state: Michigan
city: Maplewood
country: United States
facility: Minnesota Gastroenterlogy, P.A.
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center, Fairview
state: Minnesota
city: Jackson
country: United States
facility: Southern Therapy and Advance Research (STAR) LLC
state: Mississippi
city: Tupelo
country: United States
facility: Digestive Health Specialists PA
state: Mississippi
city: Kansas City
country: United States
facility: Kansas City Research Institute
state: Missouri
city: New York
country: United States
facility: Concorde Medical Group
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Center for Liver Disease and Transplantation
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Asheville
country: United States
facility: Asheville Gastroenterology Associates, a Division of Digestive Health Partners, P.A.
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: UH Cleveland Medical Center
state: Ohio
city: Bethlehem
country: United States
facility: Northeast Clinical Research Center, LLC
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Milton S Hershey Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Germantown
country: United States
facility: Gastro One
state: Tennessee
city: Knoxville
country: United States
facility: GIA Clinical Trials, LLC
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Liver Institute at Methodist Dallas
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Fort Worth
country: United States
facility: Texas Digestive Disease Consultants
state: Texas
city: Houston
country: United States
facility: American Research Corporation
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: San Antonio
country: United States
facility: American Research Corporation at Texas Liver Institute
state: Texas
city: San Antonio
country: United States
facility: Pinnacle Clinical Research
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Newport News
country: United States
facility: Mary Immaculate Hospital
state: Virginia
city: Richmond
country: United States
facility: Bon Secours Richmond Community Hospital
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Pilar
country: Argentina
facility: Hospital Universitario Austral
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Fundación Sanatorio Güemes
state: Ciudad Autónoma De BuenosAires
city: Rosario
country: Argentina
facility: Hospital Provincial Del Centenario
state: Santa Fe
city: Ramos Mejía
country: Argentina
facility: DIM Clínica Privada
city: Garran
country: Australia
facility: The Canberra Hospital
state: Australian Capital Territory
city: Herston
country: Australia
facility: Royal Brisbane & Women's Hospital
state: Queensland
city: Fitzroy
country: Australia
facility: St Vincents Hospital Melbourne
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Vienna
country: Austria
facility: Medizinische Universitat Wien
state: Wien
city: Graz
country: Austria
facility: LKH-Universitätsklinikum Klinikum Graz
city: Salzburg
country: Austria
facility: Salzburger Landeskliniken
city: Wels
country: Austria
facility: Klinikum Wels-Grieskirchen GmbH
city: Edegem
country: Belgium
facility: UZ Antwerpen
state: Antwerpen
city: Gent
country: Belgium
facility: UZ Gent
state: Oost-Vlaanderen
city: Leuven
country: Belgium
facility: UZ Leuven
state: Vlaams Brabant
city: Calgary
country: Canada
facility: University of Calgary Medicine
state: Alberta
city: Winnipeg
country: Canada
facility: University of Manitoba
state: Manitoba
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Vaughan
country: Canada
facility: Toronto Digestive Disease Associates Inc
state: Ontario
city: Montréal
country: Canada
facility: McGill University Health Centre (MUHC)
state: Quebec
city: Santiago
country: Chile
facility: Pontificia Universidad Catolica de Chile
state: Región-MetropolitanadeSantiago
city: La Serena
country: Chile
facility: Centro Clinico Mediterraneo
city: Viña Del Mar
country: Chile
facility: Centro de Investigaciones Clínicas Vina del Mar
city: Bondy
country: France
facility: Hôpital Jean Verdier
city: Grenoble
country: France
facility: CHU de GRENOBLE
city: Paris
country: France
facility: Hôpital Saint Antoine
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
state: Baden-Württemberg
city: Herne
country: Germany
facility: Gastroenterologische Gemeinschaftspraxis Herne
state: Nordrhein-Westfalen
city: Köln
country: Germany
facility: Uniklinik Köln
state: Nordrhein-Westfalen
city: Kiel
country: Germany
facility: Gastroenterologisch Hepatologisches Zentrum Kiel
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
city: Hamburg
country: Germany
facility: ifi-Institute for Interdisciplinary Medicine
city: Leipzig
country: Germany
facility: Universitatsklinikum Leipzig
city: Heraklion
country: Greece
facility: University General Hospital of Heraklion
city: Larissa
country: Greece
facility: University General Hospital of Larissa
city: Patras
country: Greece
facility: University General Hospital of Patras
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
state: Csongrád
city: Budapest
country: Hungary
facility: Budai Hepatológiai Centrum
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Kaposvár
country: Hungary
facility: Somogy Megyei Kaposi Mór Oktató Kórház
city: Hadera
country: Israel
facility: Hillel Yaffe Medical Center
city: Haifa
country: Israel
facility: Carmel Medical Center
city: Haifa
country: Israel
facility: Rambam Health Corporation
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Nahariya
country: Israel
facility: The Galilli Medical Center
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Reẖovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
city: Milano
country: Italy
facility: ASST Santi Paolo e Carlo - Azienda Universitaria-Polo Universitario San Paolo
city: Modena
country: Italy
facility: Ospedale Civile di Baggiovara
city: Padova
country: Italy
facility: Azienda Ospedaliera Di Padova
city: Rozzano
country: Italy
facility: ASST di Monza - Azienda Ospedaliera San Gerardo
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggido
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Inje University Ilsan Paik Hospital
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Pachuca de Soto
country: Mexico
facility: Centro de Diabetes y Obesidad Graber
state: Hidalgo
city: Ciudad de Mexico
country: Mexico
facility: Consultorio Medico - Distrito Federal
city: Metepec
country: Mexico
facility: Consultorio de la Doctora Maria Sarai Gonzalez Huezo
city: Nijmegen
country: Netherlands
facility: Radboud Universitair Medisch Centrum
state: Gelderland
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
state: South Island
city: Dunedin
country: New Zealand
facility: Dunedin Hospital
state: South Island
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Bydgoszcz
country: Poland
facility: Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza w Bydgoszczy
state: Kujawsko-pomorskie
city: Warszawa
country: Poland
facility: Centrum Onkologii Instytut im. Marii Sklodowskiej-Curie
state: Mazowieckie
city: Katowice
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 7 Slaskiego Uniwersytetu Medycznego w Katowicach
state: Slaskie
city: Kielce
country: Poland
facility: Wojewodzki Szpital Zespolony w Kielcach
city: Kraków
country: Poland
facility: SP ZOZ Szpital Uniwersytecki w Krakowie
city: Mysłowice
country: Poland
facility: ID Clinic
city: Timişoara
country: Romania
facility: Pius Brinzeu Emergency Clinical County Hospital
state: Timis
city: Bucharest
country: Romania
facility: Colentina Clinical Hospital
city: Bucharest
country: Romania
facility: Fundeni Clinical Institute
city: Bucharest
country: Romania
facility: Sana Monitoring SRL
city: Moscow
country: Russian Federation
facility: Peoples Friendship University of Russia
state: Moskva
city: St. Petersburg
country: Russian Federation
facility: City Hospital #31
city: Ulyanovsk
country: Russian Federation
facility: Ulyanovsk Regional Clinical Hospital
city: Belgrade
country: Serbia
facility: Clinical Hospital Centar Zvezdara
city: Belgrade
country: Serbia
facility: KBC Zemun
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro - Majadahonda
state: Madrid
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebrón - PPDS
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: Portsmouth
country: United Kingdom
facility: Queen Alexandra Hospital
state: Hampshire
city: Birmingham
country: United Kingdom
facility: University Hospital Birmingham
city: Hull
country: United Kingdom
facility: Hull and East Yorkshire Hospitals NHS Trust
city: London
country: United Kingdom
facility: Barts Health NHS Trust, Royal London Hospital, Ambrose King Centre
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust
city: London
country: United Kingdom
facility: Kings College Hospital
city: Newcastle
country: United Kingdom
facility: The Newcastle Upon Tyne Hospital NHS Foundation Trust
city: Nottingham
country: United Kingdom
facility: University of Nottingham
city: Plymouth
country: United Kingdom
facility: Plymouth Hospitals NHS Trust
city: Swansea
country: United Kingdom
facility: Singleton Hospital
Study officials:
References: