A Study Evaluating the Effects of Two Doses of MBX-8025 Compared to a Placebo in Patients with Primary Biliary Cirrhosis (PBC) who have not responded to previous treatment with ursodeoxycholic acid (UDCA).

Phase 1

Conditions: Primary Biliary Cirrhosis
MedDRA version: 18.1Level: LLTClassification code 10036680Term: Primary biliary cirrhosisSystem Organ Class: 100000004871
Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Registration Number: EUCTR2015-002698-39-GB

Lead Sponsor: CymaBay Therapeutics Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 41

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 AMA (Anti-Mitochondrial Antibodies) titers (>1/40 on immunofluorescence or M2 positive by 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 six 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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 25

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 = 2 times ULN
3. Total bilirubin >2 times ULN
4. Auto-immune hepatitis
5. Primary sclerosing cholangitis
6. Known histroy of alpha-1-Antitrypsin deficiency
7. Known history of chronic viral hepatitis
8. Creatine kinase above ULN
9. For females, pregnancy or breast-feeding
10. Use of colchicine, methotrexate, azathioprine or systemic steroids in the two months preceding screening
11. Use of an experimental treatment for PBC
12. Use of an experimental or unapproved immunosuppressant
13. 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 & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this study is to evaluate the effect of MBX-8025 on AP levels.;Secondary Objective: The secondary objectives of this study are:<br>1. To evaluate the safety and tolerability of MBX-8025 in subjects with PBC<br>2. To evaluate the effects of MBX-8025 on PBC response criteria <br>3. To evaluate the effects of MBX-8025 on other markers of liver function, lipids, pruritus and Quality of Life (QoL)<br>;Primary end point(s): To evaluate the effect of MBX-8025 on Alkaline Phosphatase (AP) Levels ;Timepoint(s) of evaluation of this end point: End of Treatment - Week 12

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Composite endpoint of AP and Total Bilirubin: <br>• AP < 1.67 ULN and Total Bilirubin within normal limit <br>and<br>• > 15% decrease in AP<br>2. Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Gamma-Glutamyl Transpeptidase (GGT), 5’nucleotidase, Bilirubin (Total, Conjugated, Unconjugated), and bone-specific AP<br>Triglycerides (TG), Total Cholesterol (TC), High Density Lipoprotein Cholesterol (HDL-C), and Low Density Lipoprotein Cholesterol (LDL-C).<br>3. Published PBC response criteria (Paris I and II, Toronto I and II), UK-PBC risk score<br>4. 5D-itch scale, pruritus VAS<br>5. PBC-40 QoL<br>;Timepoint(s) of evaluation of this end point: Visit 2 (Week 0), Visit 3 (Week 2), Visit 4 (Week 4), Visit 5 (Week 8), Visit 6 (Week 12).

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