Study to Evaluate the Effects of Two Doses of MBX-8025 in Subjects With Primary Biliary Cirrhosis (PBC)

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)

A 12-week, double-blind, randomized, placebo-controlled, Phase 2 study, to evaluate the effects of two doses of seladelpar/MBX-8025 in subjects with Primary Biliary Cirrhosis (PBC) and an inadequate response to ursodeoxycholic acid (UDCA)

Study Overview

• Status: Terminated
• Conditions: Primary Biliary Cirrhosis (PBC)
• Intervention / Treatment: Drug: Placebo Comparator; Drug: Experimental: Seladelpar / MBX-8025 50 mg; Drug: Experimental: Seladelpar / MBX-8025 200 mg

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)

Exploratory:

To evaluate the effect of MBX-8025 on liver imaging and other biochemical markers that may be relevant to the pathophysiology of PBC or the mechanism of action of the drug

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • University of Calgary Liver Unit (Heritage Medical Research Clinic)
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital
• Germany
  • Berlin, Germany, 10969
    • Leber- und Studienzentrum am Checkpoint
  • Berlin, Germany, 10117
    • Charité Universitätsmedizin Berlin - Campus Mitte
  • Bonn, Germany, 53127
    • Universitätsklinikum Bonn
  • Dresden, Germany, 01307
    • Universitätsklinikum Carl Gustav Carus an der TU Dresden
  • Erlangen, Germany, 91054
    • University Hospital Erlangen
  • Essen, Germany, 45157
    • Universitatsklinikum Essen, Zentrum fur Innere Medizin
  • Hamburg, Germany, 20099
    • Ifi-Studien und Projekte GmbH, A.d. Asklepios Klinik St. Georg
  • Hamburg, Germany, 20246
    • Universitatsklinikum Hamburg-Eppendorf MARTINISTRASSE 52
  • Hannover, Germany, 30625
    • Med. Hochschule Hannover, Klinik fur Gastroenterologie
  • Heidelberg, Germany, 69120
    • Medizinische Universitätsklinik
  • Herne, Germany, 44623
    • Gastroenterologische Gemeinschaftspraxis Herne
  • Kiel, Germany, 24105
    • UKSH, Campus Kiel, Klinik fur Allgemeine Innere Medizin 1
  • Kiel, Germany, 24105
    • UKSH, Campus Kiel
  • Leipzig, Germany, 04103
    • Universitätsklinikum Leipzig AöR
  • Mainz, Germany, 55131
    • Universitätsmedizin der Johannes Gutenberg - Universität Mainz
• Poland
  • Kujawsko-pomorskie
    • Bydgoszcz, Kujawsko-pomorskie, Poland, 85-030
      • Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza w Bydgoszczy
  • Malopolski
    • Krakow, Malopolski, Poland, 31-531
      • SPZOZ Szpital Uniwersytecki w Krakowie
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 02-781
      • Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie
  • Slaskie
    • Katowice, Slaskie, Poland, 40-752
      • SP CSK im. Prof. K. Gibinskiego SUM w Katowicach
    • Myslowice, Slaskie, Poland, 41-400
      • ID Clinic Arkadiusz Pisula
• United Kingdom
  • Birmingham, United Kingdom, B15 2GW
    • University Hospital Birmingham NHS Foundation Trust
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrooke Hospital
  • Hull, United Kingdom, HU3 2jZ
    • Hull and East Yorkshire NHS Trust
  • Newcastle upon Tyne, United Kingdom, NE1 4LP
    • The Newcastle upon Tyne Hospitals NHS Foundation Trust
  • Nottingham, United Kingdom, NG7 2UH
    • Nottingham University Hospitals NHS Trust
  • England
    • Plymouth, England, United Kingdom, PL6 8DH
      • Derriford Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic of Arizona
  • California
    • Sacramento, California, United States, 95817
      • University of California, Davis Medical Center
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Miami, Florida, United States, 33136
      • University of Miami, Center for Liver Diseases
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Norman Gitlin, MD
    • Atlanta, Georgia, United States, 30309
      • Digestive Helathcare of Georgia
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Hospital - Clinical Research Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
    • Wyoming, Michigan, United States, 49519
      • Gastroenterology Associates of Western Michigan, PLC, d.b.a. West Michigan Clinical Research
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • Kansas City Gastroenterology and Hepatology
    • Saint Louis, Missouri, United States, 63110
      • St. Louis University School of Medicine
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center / The Nebraska Medical Center
  • New York
    • Manhasset, New York, United States, 11030
      • North Shore-Long Island Jewish Health System / Division of Gastroenterology
    • New York, New York, United States, 10016
      • NYU Langone Medical Center
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai - The Mount Sinai Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45249
      • Consultants for Clinical Research
  • Texas
    • Houston, Texas, United States, 77030
      • CHI St. Luke's Health Baylor College of Medicine Medical Center - Advanced Liver Therapies
    • Live Oak, Texas, United States, 78233
      • Pinnacle Clinical Research
    • San Antonio, Texas, United States, 78215
      • American Research Corporation at Texas Liver Institute
  • Virginia
    • Newport News, Virginia, United States, 23602
      • Bon Secours St. Mary's Hospital of Richmond
    • Norfolk, Virginia, United States, 23502
      • Digestive and Liver Disease Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 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. AST or 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Dose; Placebo Capsule Two Capsules Daily	Drug: Placebo Comparator; Placebo Capsule (2 taken once daily); Other Names: Placebo
Experimental: Seladelpar / MBX-8025 50 mg Dose; MBX-8025 50 mg capsule One Capsule Daily	Drug: Experimental: Seladelpar / MBX-8025 50 mg; MBX-8025 50 mg capsule (1 taken once daily); Other Names: MBX-8025 50 mg dose
Experimental: Seladelpar / MBX-8025 200 mg Dose; MBX-8025 100 mg capsules (2 taken once daily)	Drug: Experimental: Seladelpar / MBX-8025 200 mg; MBX-8025 100 mg capsules (2 taken once daily); Other Names: MBX-8025 100 mg capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Serum Alkaline Phosphatase (AP)	12-Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite Endpoint of AP and Bilirubin	AP < 1.67 × upper limit of normal (ULN) and Total Bilirubin within normal limit and; > 15% decrease in AP	12-Weeks
Laboratory Values	Aspartate aminotransferase (AST)	12-Weeks
Laboratory Values	Alanine aminotransferase (ALT)	12-Weeks
Laboratory Values	Gamma-glutamyl transferase (GGT)	12-Weeks
Laboratory Values	5'nucleotidase	12-Weeks
Laboratory Values	Bilirubin (Total, Conjugated, Unconjugated)	12-Weeks
Laboratory Values	Bone-specific AP	12-Weeks
Laboratory Values	Triglycerides (TG)	12-Weeks
Laboratory Values	Total Cholesterol (TC)	12-Weeks
Laboratory Values	High Density Lipoprotein Cholesterol (HDL-C)	12-Weeks
Laboratory Values	Low Density Lipoprotein Cholesterol (LDL-C)	12-Weeks
Published PBC response criteria	Paris I	12-Weeks
Published PBC response criteria	Paris II	12-Weeks
Published PBC response criteria	Toronto I	12-Weeks
Published PBC response criteria	Toronto II	12-Weeks
Published PBC response criteria	United Kingdom (UK) UK-PBC risk score	12-Weeks
5D-itch scale		12-Weeks
Visual Analog Score (VAS)		12-Weeks
PBC-40 Quality of Life (QoL)		12-Weeks

Collaborators and Investigators

• Sponsor: CymaBay Therapeutics, Inc.
• Investigators: Study Chair: Pol F Boudes, M.D., CymaBay Therapeutics, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2015
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: November 13, 2015
• First Submitted That Met QC Criteria: November 18, 2015
• First Posted (Estimate): November 20, 2015

Study Record Updates

• Last Update Posted (Actual): January 29, 2018
• Last Update Submitted That Met QC Criteria: January 25, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: PBC
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Biliary Tract Diseases; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Fibrosis; Liver Cirrhosis; Liver Cirrhosis, Biliary; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Seladelpar
• Other Study ID Numbers: CB8025-21528