A clinical trial to assess the safety and efficacy of seladelpar in patients with primary biliary cholangitis (PBC) and an inadequate response to or intolerance to ursodeoxycholic acid (UDCA).

• Register: EUCTR
• Last refreshed on: 1 February 2020
• Main ID: EUCTR2018-001171-20-FR
• Date of registration: 18/10/2018
• Prospective Registration: Yes
• Primary sponsor: CymaBay Therapeutics, Inc.
• Public title: A clinical trial to assess the safety and efficacy of seladelpar in patients with primary biliary cholangitis (PBC) and an inadequate response to or intolerance to ursodeoxycholic acid (UDCA).
• Scientific title: A 52-week, placebo-controlled, randomized, Phase 3 study to evaluate the safety and efficacy of seladelpar in subjects with primary biliary cholangitis (PBC) and an inadequate response to or intolerance to ursodeoxycholic acid (UDCA).
• Date of first enrolment: 23/01/2019
• Target sample size: 240
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-001171-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Austria, Belgium, Brazil, Canada, France, Germany, Greece, Hungary, Israel, Italy, Korea, Republic of, Mexico, Netherlands, Poland, Romania, Russian Federation, Serbia, Spain, United Kingdom, United States

Contacts

• Name: Senior VP, RA&QA - Klara Dickinson
• Affiliation: CymaBay Therapeutics, Inc.

• Name: Senior VP, RA&QA - 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 6 months
• Positive anti-mitochondrial antibody (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 12 months OR intolerant to UDCA (last dose of UDCA > 3 months prior to Screening)
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 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion criteria:
1. Previous exposure to seladelpar (MBX-8025)
2. 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)
3. AST above 3 × ULN
4. ALT above 3 × ULN
5. Total bilirubin above 2.0 × ULN
6. Advanced PBC as defined by the Rotterdam criteria (albumin below LLN AND total bilirubin above 1 × ULN
7. Creatine kinase (CK) above 1.0 × ULN
8. eGFR below 60 mL/min/1.73 m2 (calculated by MDRD formula)
7. Serum creatinine above 1.0 × ULN
9. International normalized ratio (INR) above 1.0 × ULN
10. Platelet count below 100 × 103/µL
11. Presence of clinically significant hepatic decompensation, including:
- History of liver transplantation, current placement on liver transplantation list, or current Model for End-Stage Liver Disease (MELD) score = 15
- Complications of portal hypertension, including known esophageal varices, history of variceal bleeds or related interventions (e.g., transjugular intrahepatic portosystemic shunt placement), relevant ascites, hepatic encephalopathy
- Cirrhosis with complications, including history or presence of spontaneous bacterial peritonitis
12. Other chronic liver diseases:
a.Current features of auto-immune hepatitis as determined by the investigator based on immunoserology, liver biochemistry and histology
b.Primary sclerosing cholangitis determined by presence of diagnostic cholangiographic findings
c.History or clinical evidence of alcoholic liver disease
d.History or clinical evidence of alpha-1-antitrypsin deficiency
e.Biopsy confirmed nonalcoholic steatohepatitis
f.History or evidence of Gilbert’ Syndrome with elevated total bilirubin
g.History or evidence of hemochromatosis
h.Hepatitis B defined as presence of hepatitis B surface antigen (HBsAg)
i.Hepatitis C defined as presence of HCV RNA
13. Known history of HIV
14. Evidence of significant alcohol consumption
15. Evidence of drug abuse
16. Subjects with inadequate response to obeticholic acid (OCA) or intolerance to OCA: OCA must be discontinued 30 days prior to Screening
17. Use of colchicine, methotrexate, azathioprine, or long-term systemic corticosteroids (> 2 weeks) within two months prior to Screening
18. Use of fibrates within 30 days prior to Screening
19. Use of simvastatin within 7 days prior to Screening
20. Use of an experimental or unapproved treatment for PBC within 30 days prior to Screening
21. Use of experimental or unapproved immunosuppressant within 30 days prior to Screening
22. Treatment with any other investigational therapy or device within 30 days or within five half-lives, whatever is longer, prior to Screening
23. For females, pregnancy or breast-feeding
24. 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

Primary biliary cholangitis (PBC, formerly known as primary biliary cirrhosis) is a serious and potentially life threatening autoimmune disease of the liver characterized by impaired bile flow (cholestasis) and accumulation of toxic bile acids (BA).

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

Intervention(s)

Product Name: Seladelpar
Product Code: MBX-8025
Pharmaceutical Form: Capsule
INN or Proposed INN: SELADELPAR
CAS Number: 928821-40-3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Product Name: Seladelpar
Product Code: MBX-8025
Pharmaceutical Form: Capsule
INN or Proposed INN: SELADELPAR
CAS Number: 928821-40-3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 1- 12 months
2 - Throughout the study

Secondary Objective: Evaluate the effect of seladelpar on normalization of alkaline phosphate (AP) levels and to evaluate the effect of seladelpar on pruritus.
Evaluate the effect of seladelpar on quality of life (QoL), to evaluate the effect of seladelpar on other measures of cholestasis, metabolic outcomes, PBC prognosis criteria, and the effect of seladelpar on PBC clinical outcomes.

Primary end point(s): 1 - Response on the composite endpoint of AP and total bilirubin at 12 months:
o AP < 1.67 × ULN,
o = 15% decrease in AP, and
o Total bilirubin = ULN
2 - Assessment of treatment-emergent AEs (TEAEs) (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] Version 4.0), biochemistry and hematology

Main Objective: Evaluate the safety and effect on cholestasis of two seladelpar regimens (5 mg/day titrated to 10 mg/day and 10 mg/day) over 52 weeks of treatment compared to placebo.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1 - 12 months
2 - 6 months

Secondary end point(s): 1 - Proportion of patients with AP =1.0 × ULN at 12 months
2 - Change from baseline in pruritus NRS at 6 months

Secondary ID(s)

CB8025-31735

2018-001171-20-GR

NCT03602560

Source(s) of Monetary Support

CymaBay Therapeutics, Inc.

Ethics review

Status: Approved
Approval date: 23/01/2019
Contact: