A study evaluating the safety and efficacy of MBX-8025 in subjects with Primary Biliary Cholangitis (PBC) and an inadequate response to or intolerance to ursodeoxycholic acid (UDCA)

• Register: EUCTR
• Last refreshed on: 16 December 2019
• Main ID: EUCTR2016-002996-91-GB
• Date of registration: 21/11/2016
• Prospective Registration: Yes
• Primary sponsor: CymaBay Therapeutics, Inc.
• Public title: A study evaluating the safety and efficacy of MBX-8025 in subjects with Primary Biliary Cholangitis (PBC) and an inadequate response to or intolerance to ursodeoxycholic acid (UDCA)
• Scientific title: An 8-week, dose ranging, open label, randomized, Phase 2 study with a 44-week extension, to evaluate the safety and efficacy of MBX-8025 in subjects with Primary Biliary Cholangitis (PBC) and an inadequate response to or intolerance to ursodeoxycholic acid (UDCA)
• Date of first enrolment: 12/01/2017
• Target sample size: 128
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-002996-91
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: yes Other trial design description: Cohort management If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Canada, Germany, United Kingdom, United States

Contacts

• Name: Klara Dickinson
• Affiliation: CymaBay Therapeutics, Inc.

• Name: Klara Dickinson
• Affiliation: CymaBay Therapeutics, Inc.

Key inclusion & exclusion 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 ULN for at least six months
•Positive 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 or intolerant to UDCA
5.AP = 1.67 × ULN
6.Females of reproductive potential must use at least one barrier contraceptive and a second effective birth control method during the study and for at least 90 days after the last dose. Male subjects who are sexually active with female partners of reproductive potential must use barrier contraception and their female partners must use a second effective birth control method during the study and for at least 90 days 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 96
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 32

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 or simvastatin
13.Current use of obeticholic acid
14.Use of an experimental or unapproved treatment for PBC
15.Use of experimental or unapproved immunosuppressant
16.Adverse event leading to MBX-8025 discontinuation from CymaBay’s phase 2 PBC study CB8025-21528
17.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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Primary Biliary Cholangitis
MedDRA version: 20.1 Level: LLT Classification code 10036680 Term: Primary biliary cirrhosis System Organ Class: 100000004871

Intervention(s)

Product Name: Seladelpar
Product Code: MBX-8025
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Seladelpar
CAS Number: 928821-40-3
Current Sponsor code: MBX-8025
Other descriptive name: MBX-8025
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Product Name: Seladelpar
Product Code: MBX-8025
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Seladelpar
CAS Number: 928821-40-3
Other descriptive name: MBX-8025
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Product Name: Seladelpar
Product Code: MBX-8025
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Seladelpar
CAS Number: 928821-40-3
Current Sponsor code: MBX-8025
Other descriptive name: MBX-8025
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Product Name: Seladelpar
Product Code: MBX-8025
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Seladelpar
CAS Number: 928821-40-3
Current Sponsor code: MBX-8025
Other descriptive name: MBX-8025
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-

Primary Outcome(s)

Secondary Objective: To evaluate the safety and efficacy of MBX-8025 2 mg, 5 mg, 10 mg, and 20 mg over 12 and 26 weeks of treatment
To evaluate the safety and efficacy of MBX-8025 2 mg, 5 mg, 10 mg, and 20 mg over 52 weeks of treatment
To evaluate the pharmacokinetics (PK) of MBX-8025

Main Objective: To evaluate the safety and efficacy of MBX-8025 2mg, 5 mg, 10 mg, and 20 mg over 8 weeks of treatment

Timepoint(s) of evaluation of this end point: Between V1 and V2 (Week-2 and Day 1) for the primary analysis and as
V2 (Day 1) values for other analyses.

Primary end point(s): 1.Serum alkaline phosphatase (AP)
2.Adverse events (AE) and Treatment Emergent Adverse Events (TEAEs), ECG, biochemistry ,hematology, and urinalysis(NCI CTCAE Version 4.0)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Baseline to the end of extension (52-week treatment)

Secondary end point(s): 1. Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Gamma-glutamyl transferase (GGT), 5’nucleotidase, Bilirubin (Total, Conjugated, Unconjugated), Bone-specific AP, Triglycerides (TG), Total Cholesterol (TC), High Density Lipoprotein Cholesterol (HDL-C), and Low Density Lipoprotein Cholesterol (LDL-C)
2.Composite endpoint of AP and Total Bilirubin:
•AP < 1.67 × upper limit of normal (ULN)
•Total Bilirubin within normal limit
•> 15% decrease in AP
3.Published PBC response criteria (Paris I and II, Toronto I and II), UK-PBC risk score
4.5D-itch scale and pruritus Visual Analog Score (VAS)
5.PBC-40 QoL
6.PK of MBX-8025 and metabolites (at 0, 0.5, 1, 2, 4, 6 and 24 hours for Cmax, Tmax, T1/2 and AUC; trough level)

Secondary ID(s)

CB8025-21629

2016-002996-91-DE

Source(s) of Monetary Support

CymaBay Therapeutics, Inc.

Ethics review

Status: Approved
Approval date:
Contact: