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

Primary Purpose

Primary Biliary Cirrhosis (PBC)

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Placebo Comparator
Experimental: Seladelpar / MBX-8025 50 mg
Experimental: Seladelpar / MBX-8025 200 mg
Sponsored by
CymaBay Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Biliary Cirrhosis (PBC) focused on measuring PBC

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic of Arizona
  • University of California, Davis Medical Center
  • University of Florida
  • University of Miami, Center for Liver Diseases
  • Norman Gitlin, MD
  • Digestive Helathcare of Georgia
  • Indiana University Hospital - Clinical Research Center
  • Henry Ford Health System
  • Gastroenterology Associates of Western Michigan, PLC, d.b.a. West Michigan Clinical Research
  • Kansas City Gastroenterology and Hepatology
  • St. Louis University School of Medicine
  • University of Nebraska Medical Center / The Nebraska Medical Center
  • North Shore-Long Island Jewish Health System / Division of Gastroenterology
  • NYU Langone Medical Center
  • Icahn School of Medicine at Mount Sinai - The Mount Sinai Medical Center
  • Consultants for Clinical Research
  • CHI St. Luke's Health Baylor College of Medicine Medical Center - Advanced Liver Therapies
  • Pinnacle Clinical Research
  • American Research Corporation at Texas Liver Institute
  • Bon Secours St. Mary's Hospital of Richmond
  • Digestive and Liver Disease Specialists
  • University of Calgary Liver Unit (Heritage Medical Research Clinic)
  • Toronto General Hospital
  • Charite Universitatsmedizin Berlin - Campus Mitte
  • Leber- und Studienzentrum am Checkpoint
  • Universitatsklinikum Bonn
  • Universitatsklinikum Carl Gustav Carus an der TU Dresden
  • University Hospital Erlangen
  • Universitatsklinikum Essen, Zentrum fur Innere Medizin
  • Ifi-Studien und Projekte GmbH, A.d. Asklepios Klinik St. Georg
  • Universitatsklinikum Hamburg-Eppendorf MARTINISTRASSE 52
  • Med. Hochschule Hannover, Klinik fur Gastroenterologie
  • Medizinische Universitatsklinik
  • Gastroenterologische Gemeinschaftspraxis Herne
  • UKSH, Campus Kiel, Klinik fur Allgemeine Innere Medizin 1
  • UKSH, Campus Kiel
  • Universitatsklinikum Leipzig AOR
  • Universitatsmedizin der Johannes Gutenberg - Universitat Mainz
  • Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza w Bydgoszczy
  • SPZOZ Szpital Uniwersytecki w Krakowie
  • Centrum Onkologii-Instytut Im. Marii Sklodowskiej-Curie
  • SP CSK im. Prof. K. Gibinskiego SUM w Katowicach
  • ID Clinic Arkadiusz Pisula
  • Derriford Hospital
  • University Hospital Birmingham NHS Foundation Trust
  • Addenbrooke Hospital
  • Hull and East Yorkshire NHS Trust
  • The Newcastle upon Tyne Hospitals NHS Foundation Trust
  • Nottingham University Hospitals NHS Trust

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Experimental

Experimental

Arm Label

Placebo Dose

Seladelpar / MBX-8025 50 mg Dose

Seladelpar / MBX-8025 200 mg Dose

Arm Description

Placebo Capsule Two Capsules Daily

MBX-8025 50 mg capsule One Capsule Daily

MBX-8025 100 mg capsules (2 taken once daily)

Outcomes

Primary Outcome Measures

Serum Alkaline Phosphatase (AP)

Secondary Outcome Measures

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
Laboratory Values
Aspartate aminotransferase (AST)
Laboratory Values
Alanine aminotransferase (ALT)
Laboratory Values
Gamma-glutamyl transferase (GGT)
Laboratory Values
5'nucleotidase
Laboratory Values
Bilirubin (Total, Conjugated, Unconjugated)
Laboratory Values
Bone-specific AP
Laboratory Values
Triglycerides (TG)
Laboratory Values
Total Cholesterol (TC)
Laboratory Values
High Density Lipoprotein Cholesterol (HDL-C)
Laboratory Values
Low Density Lipoprotein Cholesterol (LDL-C)
Published PBC response criteria
Paris I
Published PBC response criteria
Paris II
Published PBC response criteria
Toronto I
Published PBC response criteria
Toronto II
Published PBC response criteria
United Kingdom (UK) UK-PBC risk score
5D-itch scale
Visual Analog Score (VAS)
PBC-40 Quality of Life (QoL)

Full Information

First Posted
November 13, 2015
Last Updated
January 25, 2018
Sponsor
CymaBay Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02609048
Brief Title
Study to Evaluate the Effects of Two Doses of 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

2. Study Status

Record Verification Date
January 2018
Overall Recruitment Status
Terminated
Why Stopped
Study stopped early after review of safety and efficacy demonstrated efficacy proof-of-concept and need for dose reduction.
Study Start Date
November 2015 (Actual)
Primary Completion Date
July 2016 (Actual)
Study Completion Date
July 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CymaBay Therapeutics, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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)
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Biliary Cirrhosis (PBC)
Keywords
PBC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
41 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo Dose
Arm Type
Placebo Comparator
Arm Description
Placebo Capsule Two Capsules Daily
Arm Title
Seladelpar / MBX-8025 50 mg Dose
Arm Type
Experimental
Arm Description
MBX-8025 50 mg capsule One Capsule Daily
Arm Title
Seladelpar / MBX-8025 200 mg Dose
Arm Type
Experimental
Arm Description
MBX-8025 100 mg capsules (2 taken once daily)
Intervention Type
Drug
Intervention Name(s)
Placebo Comparator
Other Intervention Name(s)
Placebo
Intervention Description
Placebo Capsule (2 taken once daily)
Intervention Type
Drug
Intervention Name(s)
Experimental: Seladelpar / MBX-8025 50 mg
Other Intervention Name(s)
MBX-8025 50 mg dose
Intervention Description
MBX-8025 50 mg capsule (1 taken once daily)
Intervention Type
Drug
Intervention Name(s)
Experimental: Seladelpar / MBX-8025 200 mg
Other Intervention Name(s)
MBX-8025 100 mg capsules
Intervention Description
MBX-8025 100 mg capsules (2 taken once daily)
Primary Outcome Measure Information:
Title
Serum Alkaline Phosphatase (AP)
Time Frame
12-Weeks
Secondary Outcome Measure Information:
Title
Composite Endpoint of AP and Bilirubin
Description
AP < 1.67 × upper limit of normal (ULN) and Total Bilirubin within normal limit and > 15% decrease in AP
Time Frame
12-Weeks
Title
Laboratory Values
Description
Aspartate aminotransferase (AST)
Time Frame
12-Weeks
Title
Laboratory Values
Description
Alanine aminotransferase (ALT)
Time Frame
12-Weeks
Title
Laboratory Values
Description
Gamma-glutamyl transferase (GGT)
Time Frame
12-Weeks
Title
Laboratory Values
Description
5'nucleotidase
Time Frame
12-Weeks
Title
Laboratory Values
Description
Bilirubin (Total, Conjugated, Unconjugated)
Time Frame
12-Weeks
Title
Laboratory Values
Description
Bone-specific AP
Time Frame
12-Weeks
Title
Laboratory Values
Description
Triglycerides (TG)
Time Frame
12-Weeks
Title
Laboratory Values
Description
Total Cholesterol (TC)
Time Frame
12-Weeks
Title
Laboratory Values
Description
High Density Lipoprotein Cholesterol (HDL-C)
Time Frame
12-Weeks
Title
Laboratory Values
Description
Low Density Lipoprotein Cholesterol (LDL-C)
Time Frame
12-Weeks
Title
Published PBC response criteria
Description
Paris I
Time Frame
12-Weeks
Title
Published PBC response criteria
Description
Paris II
Time Frame
12-Weeks
Title
Published PBC response criteria
Description
Toronto I
Time Frame
12-Weeks
Title
Published PBC response criteria
Description
Toronto II
Time Frame
12-Weeks
Title
Published PBC response criteria
Description
United Kingdom (UK) UK-PBC risk score
Time Frame
12-Weeks
Title
5D-itch scale
Time Frame
12-Weeks
Title
Visual Analog Score (VAS)
Time Frame
12-Weeks
Title
PBC-40 Quality of Life (QoL)
Time Frame
12-Weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Must have given written informed consent (signed and dated) and any authorizations required by local law 18 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 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 On a stable and recommended dose of UDCA for the past twelve months AP ≥ 1.67 × ULN 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: 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) AST or ALT > 3 × ULN Total bilirubin > 2 × ULN Auto-immune hepatitis Primary sclerosing cholangitis Known history of alpha-1-Antitrypsin deficiency Known history of chronic viral hepatitis Creatine kinase above ULN Serum creatinine above ULN For females, pregnancy or breast-feeding Use of colchicine, methotrexate, azathioprine, or systemic steroids in the two months preceding screening Current use of fibrates, including fenofibrates, or simvastatin Use of an experimental treatment for PBC Use of experimental or unapproved immunosuppressant 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pol F Boudes, M.D.
Organizational Affiliation
CymaBay Therapeutics, Inc.
Official's Role
Study Chair
Facility Information:
Facility Name
Mayo Clinic of Arizona
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Facility Name
University of California, Davis Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
University of Miami, Center for Liver Diseases
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Norman Gitlin, MD
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30308
Country
United States
Facility Name
Digestive Helathcare of Georgia
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30309
Country
United States
Facility Name
Indiana University Hospital - Clinical Research Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Henry Ford Health System
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Gastroenterology Associates of Western Michigan, PLC, d.b.a. West Michigan Clinical Research
City
Wyoming
State/Province
Michigan
ZIP/Postal Code
49519
Country
United States
Facility Name
Kansas City Gastroenterology and Hepatology
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64131
Country
United States
Facility Name
St. Louis University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
University of Nebraska Medical Center / The Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
North Shore-Long Island Jewish Health System / Division of Gastroenterology
City
Manhasset
State/Province
New York
ZIP/Postal Code
11030
Country
United States
Facility Name
NYU Langone Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Icahn School of Medicine at Mount Sinai - The Mount Sinai Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Consultants for Clinical Research
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45249
Country
United States
Facility Name
CHI St. Luke's Health Baylor College of Medicine Medical Center - Advanced Liver Therapies
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Pinnacle Clinical Research
City
Live Oak
State/Province
Texas
ZIP/Postal Code
78233
Country
United States
Facility Name
American Research Corporation at Texas Liver Institute
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
Facility Name
Bon Secours St. Mary's Hospital of Richmond
City
Newport News
State/Province
Virginia
ZIP/Postal Code
23602
Country
United States
Facility Name
Digestive and Liver Disease Specialists
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23502
Country
United States
Facility Name
University of Calgary Liver Unit (Heritage Medical Research Clinic)
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4Z6
Country
Canada
Facility Name
Toronto General Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada
Facility Name
Charite Universitatsmedizin Berlin - Campus Mitte
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Leber- und Studienzentrum am Checkpoint
City
Berlin
ZIP/Postal Code
10969
Country
Germany
Facility Name
Universitatsklinikum Bonn
City
Bonn
ZIP/Postal Code
53127
Country
Germany
Facility Name
Universitatsklinikum Carl Gustav Carus an der TU Dresden
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
University Hospital Erlangen
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
Facility Name
Universitatsklinikum Essen, Zentrum fur Innere Medizin
City
Essen
ZIP/Postal Code
45157
Country
Germany
Facility Name
Ifi-Studien und Projekte GmbH, A.d. Asklepios Klinik St. Georg
City
Hamburg
ZIP/Postal Code
20099
Country
Germany
Facility Name
Universitatsklinikum Hamburg-Eppendorf MARTINISTRASSE 52
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Med. Hochschule Hannover, Klinik fur Gastroenterologie
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Medizinische Universitatsklinik
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Gastroenterologische Gemeinschaftspraxis Herne
City
Herne
ZIP/Postal Code
44623
Country
Germany
Facility Name
UKSH, Campus Kiel, Klinik fur Allgemeine Innere Medizin 1
City
Kiel
ZIP/Postal Code
24105
Country
Germany
Facility Name
UKSH, Campus Kiel
City
Kiel
ZIP/Postal Code
24105
Country
Germany
Facility Name
Universitatsklinikum Leipzig AOR
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Universitatsmedizin der Johannes Gutenberg - Universitat Mainz
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza w Bydgoszczy
City
Bydgoszcz
State/Province
Kujawsko-pomorskie
ZIP/Postal Code
85-030
Country
Poland
Facility Name
SPZOZ Szpital Uniwersytecki w Krakowie
City
Krakow
State/Province
Malopolski
ZIP/Postal Code
31-531
Country
Poland
Facility Name
Centrum Onkologii-Instytut Im. Marii Sklodowskiej-Curie
City
Warszawa
State/Province
Mazowieckie
ZIP/Postal Code
02-781
Country
Poland
Facility Name
SP CSK im. Prof. K. Gibinskiego SUM w Katowicach
City
Katowice
State/Province
Slaskie
ZIP/Postal Code
40-752
Country
Poland
Facility Name
ID Clinic Arkadiusz Pisula
City
Myslowice
State/Province
Slaskie
ZIP/Postal Code
41-400
Country
Poland
Facility Name
Derriford Hospital
City
Plymouth
State/Province
England
ZIP/Postal Code
PL6 8DH
Country
United Kingdom
Facility Name
University Hospital Birmingham NHS Foundation Trust
City
Birmingham
ZIP/Postal Code
B15 2GW
Country
United Kingdom
Facility Name
Addenbrooke Hospital
City
Cambridge
ZIP/Postal Code
CB2 0QQ
Country
United Kingdom
Facility Name
Hull and East Yorkshire NHS Trust
City
Hull
ZIP/Postal Code
HU3 2jZ
Country
United Kingdom
Facility Name
The Newcastle upon Tyne Hospitals NHS Foundation Trust
City
Newcastle upon Tyne
ZIP/Postal Code
NE1 4LP
Country
United Kingdom
Facility Name
Nottingham University Hospitals NHS Trust
City
Nottingham
ZIP/Postal Code
NG7 2UH
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
28818518
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.
Results Reference
derived

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

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