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

Primary Biliary Cirrhosis (PBC) Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02609048
• Other study ID #: CB8025-21528
• Status: Terminated
• Phase: Phase 2
• First received: November 13, 2015
• Last updated: January 25, 2018
• Start date: November 2015
• Est. completion date: July 2016

Study information

• Verified date: January 2018
• Source: CymaBay Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 41
• Est. completion date: July 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Fibrosis
• Liver Cirrhosis
• Liver Cirrhosis, Biliary
• Primary Biliary Cirrhosis (PBC)

Intervention

Drug:
• Placebo Comparator
Placebo Capsule (2 taken once daily)
• Experimental: Seladelpar / MBX-8025 50 mg
MBX-8025 50 mg capsule (1 taken once daily)
• Experimental: Seladelpar / MBX-8025 200 mg
MBX-8025 100 mg capsules (2 taken once daily)

Locations

Country	Name	City	State
Canada	University of Calgary Liver Unit (Heritage Medical Research Clinic)	Calgary	Alberta
Canada	Toronto General Hospital	Toronto	Ontario
Germany	Charite Universitatsmedizin Berlin - Campus Mitte	Berlin
Germany	Leber- und Studienzentrum am Checkpoint	Berlin
Germany	Universitatsklinikum Bonn	Bonn
Germany	Universitatsklinikum Carl Gustav Carus an der TU Dresden	Dresden
Germany	University Hospital Erlangen	Erlangen
Germany	Universitatsklinikum Essen, Zentrum fur Innere Medizin	Essen
Germany	Ifi-Studien und Projekte GmbH, A.d. Asklepios Klinik St. Georg	Hamburg
Germany	Universitatsklinikum Hamburg-Eppendorf MARTINISTRASSE 52	Hamburg
Germany	Med. Hochschule Hannover, Klinik fur Gastroenterologie	Hannover
Germany	Medizinische Universitatsklinik	Heidelberg
Germany	Gastroenterologische Gemeinschaftspraxis Herne	Herne
Germany	UKSH, Campus Kiel	Kiel
Germany	UKSH, Campus Kiel, Klinik fur Allgemeine Innere Medizin 1	Kiel
Germany	Universitatsklinikum Leipzig AOR	Leipzig
Germany	Universitatsmedizin der Johannes Gutenberg - Universitat Mainz	Mainz
Poland	Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza w Bydgoszczy	Bydgoszcz	Kujawsko-pomorskie
Poland	SP CSK im. Prof. K. Gibinskiego SUM w Katowicach	Katowice	Slaskie
Poland	SPZOZ Szpital Uniwersytecki w Krakowie	Krakow	Malopolski
Poland	ID Clinic Arkadiusz Pisula	Myslowice	Slaskie
Poland	Centrum Onkologii-Instytut Im. Marii Sklodowskiej-Curie	Warszawa	Mazowieckie
United Kingdom	University Hospital Birmingham NHS Foundation Trust	Birmingham
United Kingdom	Addenbrooke Hospital	Cambridge
United Kingdom	Hull and East Yorkshire NHS Trust	Hull
United Kingdom	The Newcastle upon Tyne Hospitals NHS Foundation Trust	Newcastle upon Tyne
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham
United Kingdom	Derriford Hospital	Plymouth	England
United States	Digestive Helathcare of Georgia	Atlanta	Georgia
United States	Norman Gitlin, MD	Atlanta	Georgia
United States	Consultants for Clinical Research	Cincinnati	Ohio
United States	Henry Ford Health System	Detroit	Michigan
United States	University of Florida	Gainesville	Florida
United States	CHI St. Luke's Health Baylor College of Medicine Medical Center - Advanced Liver Therapies	Houston	Texas
United States	Indiana University Hospital - Clinical Research Center	Indianapolis	Indiana
United States	Kansas City Gastroenterology and Hepatology	Kansas City	Missouri
United States	Pinnacle Clinical Research	Live Oak	Texas
United States	North Shore-Long Island Jewish Health System / Division of Gastroenterology	Manhasset	New York
United States	University of Miami, Center for Liver Diseases	Miami	Florida
United States	Icahn School of Medicine at Mount Sinai - The Mount Sinai Medical Center	New York	New York
United States	NYU Langone Medical Center	New York	New York
United States	Bon Secours St. Mary's Hospital of Richmond	Newport News	Virginia
United States	Digestive and Liver Disease Specialists	Norfolk	Virginia
United States	University of Nebraska Medical Center / The Nebraska Medical Center	Omaha	Nebraska
United States	Mayo Clinic of Arizona	Phoenix	Arizona
United States	University of California, Davis Medical Center	Sacramento	California
United States	St. Louis University School of Medicine	Saint Louis	Missouri
United States	American Research Corporation at Texas Liver Institute	San Antonio	Texas
United States	Gastroenterology Associates of Western Michigan, PLC, d.b.a. West Michigan Clinical Research	Wyoming	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
CymaBay Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Canada,  Germany,  Poland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum Alkaline Phosphatase (AP)		12-Weeks
Secondary	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
Secondary	Laboratory Values	Aspartate aminotransferase (AST)	12-Weeks
Secondary	Laboratory Values	Alanine aminotransferase (ALT)	12-Weeks
Secondary	Laboratory Values	Gamma-glutamyl transferase (GGT)	12-Weeks
Secondary	Laboratory Values	5'nucleotidase	12-Weeks
Secondary	Laboratory Values	Bilirubin (Total, Conjugated, Unconjugated)	12-Weeks
Secondary	Laboratory Values	Bone-specific AP	12-Weeks
Secondary	Laboratory Values	Triglycerides (TG)	12-Weeks
Secondary	Laboratory Values	Total Cholesterol (TC)	12-Weeks
Secondary	Laboratory Values	High Density Lipoprotein Cholesterol (HDL-C)	12-Weeks
Secondary	Laboratory Values	Low Density Lipoprotein Cholesterol (LDL-C)	12-Weeks
Secondary	Published PBC response criteria	Paris I	12-Weeks
Secondary	Published PBC response criteria	Paris II	12-Weeks
Secondary	Published PBC response criteria	Toronto I	12-Weeks
Secondary	Published PBC response criteria	Toronto II	12-Weeks
Secondary	Published PBC response criteria	United Kingdom (UK) UK-PBC risk score	12-Weeks
Secondary	5D-itch scale		12-Weeks
Secondary	Visual Analog Score (VAS)		12-Weeks
Secondary	PBC-40 Quality of Life (QoL)		12-Weeks