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

Gilead Sciences

Status and phase: Terminated; Phase 2

Conditions: Primary Biliary Cirrhosis (PBC)

Treatments: Drug: Experimental: Seladelpar / MBX-8025 200 mg; Drug: Experimental: Seladelpar 50 mg; Drug: Placebo Comparator

Study type: Interventional

Funder types: Industry

Identifiers

NCT02609048

2015-002698-39 (EudraCT Number)

CB8025-21528

Details and patient eligibility

About

The primary objective of this study is to evaluate the effect of seladelpar (MBX-8025) on alkaline phosphatase (AP) levels in participants with primary biliary cirrhosis (PBC).

Full 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)

Enrollment: 41 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No 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 upper limit of normal (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. Aspartate Aminotransferase (AST) or Alanine Aminotransferase (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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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41 participants in 3 patient groups, including a placebo group

Placebo Dose

Placebo Comparator group

Description:

Participants received 2 placebo-to-match (PTM) seladelpar capsules, orally, once daily for 12 weeks.

Treatment:

Drug: Placebo Comparator

Seladelpar 50 mg Dose

Experimental group

Description:

Participants received seladelpar 50 mg capsule (1 x 50 mg capsule) and a PTM seladelpar capsule, orally, once daily for 12 weeks.

Treatment:

Drug: Placebo Comparator

Drug: Experimental: Seladelpar 50 mg

Seladelpar 200 mg Dose

Experimental group

Description:

Participants received seladelpar 200 mg capsules (2 x 100 mg capsules), orally, once daily for 12 weeks.

Treatment:

Drug: Experimental: Seladelpar / MBX-8025 200 mg