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)
Trial Snapshot
- Phase
- Phase 2
- Status
- Terminated
- Sponsor
- Gilead Sciences
- Enrollment
- 41
- Locations
- 49
- Primary Endpoint
- Baseline Alkaline Phosphatase (AP) Levels
Study Overview
Brief Summary
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).
Detailed 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)
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Must have given written informed consent (signed and dated) and any authorizations required by local law
- •18 to 75 years old (inclusive)
- •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
- •On a stable and recommended dose of UDCA for the past twelve months
- •AP ≥ 1.67 × ULN
- •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
- •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)
- •Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) > 3 × ULN
- •Total bilirubin > 2 × ULN
- •Auto-immune hepatitis
- •Primary sclerosing cholangitis
- •Known history of alpha-1-Antitrypsin deficiency
- •Known history of chronic viral hepatitis
- •Creatine kinase above ULN
- •Serum creatinine above ULN
- •For females, pregnancy or breast-feeding
- •Use of colchicine, methotrexate, azathioprine, or systemic steroids in the two months preceding screening
- •Current use of fibrates, including fenofibrates, or simvastatin
- •Use of an experimental treatment for PBC
- •Use of experimental or unapproved immunosuppressant
- •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
Arms & Interventions
Placebo Dose
Participants received 2 placebo-to-match (PTM) seladelpar capsules, orally, once daily for 12 weeks.
Intervention: Placebo Comparator (Drug)
Seladelpar 50 mg Dose
Participants received seladelpar 50 mg capsule (1 x 50 mg capsule) and a PTM seladelpar capsule, orally, once daily for 12 weeks.
Intervention: Placebo Comparator (Drug)
Outcomes
Primary Outcomes
Baseline Alkaline Phosphatase (AP) Levels
Time Frame: Baseline
Baseline for AP level was defined as the mean between assessments at Visit 1 (Week -4 to Week 0) and Visit 2 (Week 0).
Percent Change From Baseline in Alkaline Phosphatase (AP) Levels
Time Frame: Baseline, Week 12
Percent change in AP serum levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by last observation carried forward (LOCF). Baseline for AP level was defined as the mean between assessments at Visit 1 (Week -4 to Week 0) and Visit 2 (Week 0).
Secondary Outcomes
- Percentage of Participants With Response as Determined by Composite Endpoint of Alkaline Phosphatase and Total Bilirubin(Week 12)
- Percent Change From Baseline in Aspartate Aminotransferase (AST)(Baseline, Week 12)
- Percent Change From Baseline in Alanine Aminotransferase (ALT)(Baseline, Week 12)
- Percent Change From Baseline in Gamma-glutamyl Transferase (GGT)(Baseline, Week 12)
- Percent Change From Baseline in 5'Nucleotidase (5NT)(Baseline, Week 12)
- Percent Change From Baseline in Total Bilirubin(Baseline, Week 12)
- Percent Change From Baseline in Conjugated Bilirubin(Baseline, Week 12)
- Percent Change From Baseline in Unconjugated Bilirubin(Baseline, Week 12)
- Percent Change From Baseline in Bone-specific AP Levels(Baseline, Week 12)
- Percent Change From Baseline in Triglycerides (TG)(Baseline, Week 12)
- Percent Change From Baseline in Total Cholesterol (TC)(Baseline, Week 12)
- Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C)(Baseline, Week 12)
- Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C)(Baseline, Week 12)
- Number of Participants Who Were Non-responders as Determined by Published PBC Response Criteria (Paris I)(Week 12)
- Number of Participants Who Were Non-responders as Determined by Published PBC Response Criteria (Paris II)(Week 12)
- Number of Participants Who Were Non-responders as Determined by Published PBC Response Criteria (Toronto I)(Week 12)
- Number of Participants Who Were Non-responders as Determined by Published PBC Response Criteria (Toronto II)(Week 12)
- United Kingdom-Primary Biliary Cirrhosis/Cholangitis (UK-PBC) Risk Score(Week 12)
- Change From Baseline in 5-Dimension (5-D) Itch Scale Score(Baseline, Week 12)
- Change From Baseline in Pruritus Visual Analog Scale (VAS) Score(Baseline, Week 12)
- Change From Baseline in PBC-40 Quality of Life Questionnaire(Baseline, Week 12)