Clinical trial NCT02609048: Study to Evaluate the Effects of Two Doses of Seladelpar (MBX-8025) in Subjects With Primary Biliary Cirrhosis (PBC)
Official title: A 12-week, Double-blind, Randomized, Placebo-controlled, Phase 2 Study, to Evaluate the Effects of Two Doses of MBX-8025 in Subjects With Primary Biliary Cirrhosis (PBC) and an Inadequate Response to Ursodeoxycholic Acid (UDCA)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Primary Biliary Cirrhosis (PBC)
Keywords: PBC
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2015-11-20
Enrollment: 41
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: The primary objective of this study is to evaluate the effect of seladelpar (MBX-8025) on alkaline phosphatase (AP) levels in participants with primary biliary cirrhosis (PBC).

Detailed description: Primary:

To evaluate the effect of MBX-8025 on Alkaline Phosphatase (AP) levels

Secondary:

To evaluate the safety and tolerability of MBX-8025 in subjects with Primary Biliary Cirrhosis (PBC) To evaluate the effects of MBX-8025 on Primary Biliary Cirrhosis (PBC) response criteria To evaluate the effects of MBX-8025 on other markers of liver function, lipids, pruritus and Quality of Life (QoL)

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 upper limit of normal (ULN) for at least six months
   * Positive Anti-Mitochondrial Antibodies (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
5. AP ≥ 1.67 × ULN
6. For females of reproductive potential, use of at least one barrier contraceptive and a second effective birth control method during the study and for at least two weeks after the last dose. For male subjects, use of appropriate contraception (e.g., condoms), so their female partners of reproductive potential do not become pregnant during the study and for at least two weeks after the last dose

Exclusion Criteria:

1. 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 on active treatment)
2. Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) \> 3 × ULN
3. Total bilirubin \> 2 × ULN
4. Auto-immune hepatitis
5. Primary sclerosing cholangitis
6. Known history of alpha-1-Antitrypsin deficiency
7. Known history of chronic viral hepatitis
8. Creatine kinase above ULN
9. Serum creatinine above ULN
10. For females, pregnancy or breast-feeding
11. Use of colchicine, methotrexate, azathioprine, or systemic steroids in the two months preceding screening
12. Current use of fibrates, including fenofibrates, or simvastatin
13. Use of an experimental treatment for PBC
14. Use of experimental or unapproved immunosuppressant
15. 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: Baseline Alkaline Phosphatase (AP) Levels
timeFrame: Baseline
measure: Percent Change From Baseline in Alkaline Phosphatase (AP) Levels
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Percentage of Participants With Response as Determined by Composite Endpoint of Alkaline Phosphatase and Total Bilirubin
timeFrame: Week 12
measure: Percent Change From Baseline in Aspartate Aminotransferase (AST)
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in Alanine Aminotransferase (ALT)
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in Gamma-glutamyl Transferase (GGT)
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in 5'Nucleotidase (5NT)
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in Total Bilirubin
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in Conjugated Bilirubin
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in Unconjugated Bilirubin
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in Bone-specific AP Levels
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in Triglycerides (TG)
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in Total Cholesterol (TC)
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C)
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C)
timeFrame: Baseline, Week 12
measure: Number of Participants Who Were Non-responders as Determined by Published PBC Response Criteria (Paris I)
timeFrame: Week 12
measure: Number of Participants Who Were Non-responders as Determined by Published PBC Response Criteria (Paris II)
timeFrame: Week 12
measure: Number of Participants Who Were Non-responders as Determined by Published PBC Response Criteria (Toronto I)
timeFrame: Week 12
measure: Number of Participants Who Were Non-responders as Determined by Published PBC Response Criteria (Toronto II)
timeFrame: Week 12
measure: United Kingdom-Primary Biliary Cirrhosis/Cholangitis (UK-PBC) Risk Score
timeFrame: Week 12
measure: Change From Baseline in 5-Dimension (5-D) Itch Scale Score
timeFrame: Baseline, Week 12
measure: Change From Baseline in Pruritus Visual Analog Scale (VAS) Score
timeFrame: Baseline, Week 12
measure: Change From Baseline in PBC-40 Quality of Life Questionnaire
timeFrame: Baseline, Week 12
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic of Arizona
state: Arizona
city: Sacramento
country: United States
facility: University of California, Davis Medical Center
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Miami
country: United States
facility: University of Miami, Center for Liver Diseases
state: Florida
city: Atlanta
country: United States
facility: Norman Gitlin, MD
state: Georgia
city: Atlanta
country: United States
facility: Digestive Helathcare of Georgia
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University Hospital - Clinical Research Center
state: Indiana
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Wyoming
country: United States
facility: Gastroenterology Associates of Western Michigan, PLC, d.b.a. West Michigan Clinical Research
state: Michigan
city: Kansas City
country: United States
facility: Kansas City Gastroenterology and Hepatology
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center / The Nebraska Medical Center
state: Nebraska
city: Manhasset
country: United States
facility: North Shore-Long Island Jewish Health System / Division of Gastroenterology
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai - The Mount Sinai Medical Center
state: New York
city: Cincinnati
country: United States
facility: Consultants for Clinical Research
state: Ohio
city: Houston
country: United States
facility: CHI St. Luke's Health Baylor College of Medicine Medical Center - Advanced Liver Therapies
state: Texas
city: Live Oak
country: United States
facility: Pinnacle Clinical Research
state: Texas
city: San Antonio
country: United States
facility: American Research Corporation at Texas Liver Institute
state: Texas
city: Newport News
country: United States
facility: Bon Secours St. Mary's Hospital of Richmond
state: Virginia
city: Norfolk
country: United States
facility: Digestive and Liver Disease Specialists
state: Virginia
city: Calgary
country: Canada
facility: University of Calgary Liver Unit (Heritage Medical Research Clinic)
state: Alberta
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Berlin
country: Germany
facility: Charite Universitatsmedizin Berlin - Campus Mitte
city: Berlin
country: Germany
facility: Leber- und Studienzentrum am Checkpoint
city: Bonn
country: Germany
facility: Universitatsklinikum Bonn
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carus an der TU Dresden
city: Erlangen
country: Germany
facility: University Hospital Erlangen
city: Essen
country: Germany
facility: Universitatsklinikum Essen, Zentrum fur Innere Medizin
city: Hamburg
country: Germany
facility: Ifi-Studien und Projekte GmbH, A.d. Asklepios Klinik St. Georg
city: Hamburg
country: Germany
facility: Universitatsklinikum Hamburg-Eppendorf MARTINISTRASSE 52
city: Hannover
country: Germany
facility: Med. Hochschule Hannover, Klinik fur Gastroenterologie
city: Heidelberg
country: Germany
facility: Medizinische Universitatsklinik
city: Herne
country: Germany
facility: Gastroenterologische Gemeinschaftspraxis Herne
city: Kiel
country: Germany
facility: UKSH, Campus Kiel, Klinik fur Allgemeine Innere Medizin 1
city: Kiel
country: Germany
facility: UKSH, Campus Kiel
city: Leipzig
country: Germany
facility: Universitatsklinikum Leipzig AOR
city: Mainz
country: Germany
facility: Universitatsmedizin der Johannes Gutenberg - Universitat Mainz
city: Bydgoszcz
country: Poland
facility: Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza w Bydgoszczy
state: Kujawsko-pomorskie
city: Krakow
country: Poland
facility: SPZOZ Szpital Uniwersytecki w Krakowie
state: Malopolski
city: Warszawa
country: Poland
facility: Centrum Onkologii-Instytut Im. Marii Sklodowskiej-Curie
state: Mazowieckie
city: Katowice
country: Poland
facility: SP CSK im. Prof. K. Gibinskiego SUM w Katowicach
state: Slaskie
city: Myslowice
country: Poland
facility: ID Clinic Arkadiusz Pisula
state: Slaskie
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
state: England
city: Birmingham
country: United Kingdom
facility: University Hospital Birmingham NHS Foundation Trust
city: Cambridge
country: United Kingdom
facility: Addenbrooke Hospital
city: Hull
country: United Kingdom
facility: Hull and East Yorkshire NHS Trust
city: Newcastle upon Tyne
country: United Kingdom
facility: The Newcastle upon Tyne Hospitals NHS Foundation Trust
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
Study officials:
affiliation: Gilead Sciences
name: Pol F Boudes, M.D.
role: STUDY_CHAIR
References:
citation: Jones D, Boudes PF, Swain MG, Bowlus CL, Galambos MR, Bacon BR, Doerffel Y, Gitlin N, Gordon SC, Odin JA, Sheridan D, Worns MA, Clark V, Corless L, Hartmann H, Jonas ME, Kremer AE, Mells GF, Buggisch P, Freilich BL, Levy C, Vierling JM, Bernstein DE, Hartleb M, Janczewska E, Rochling F, Shah H, Shiffman ML, Smith JH, Choi YJ, Steinberg A, Varga M, Chera H, Martin R, McWherter CA, Hirschfield GM. Seladelpar (MBX-8025), a selective PPAR-delta agonist, in patients with primary biliary cholangitis with an inadequate response to ursodeoxycholic acid: a double-blind, randomised, placebo-controlled, phase 2, proof-of-concept study. Lancet Gastroenterol Hepatol. 2017 Oct;2(10):716-726. doi: 10.1016/S2468-1253(17)30246-7. Epub 2017 Aug 14.