Phase 2
N=119
Seladelpar (MBX-8025) in Subjects With Primary Biliary Cholangitis (PBC)
Primary Biliary Cirrhosis
Bottom Line
View on ClinicalTrials.gov: NCT02955602 ↗Enrolled (actual)
119
Serious AEs
11.8%
Results posted
Jul 2022
Primary outcome: Primary: Relative Change From Baseline in Serum Alkaline Phosphatase (ALP) at Week 8 — -26.06; -33.38; -41.42 percentage change from baseline — p== 0.2242
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- MBX-8025 2 mg Capsule (Drug); MBX-8025 5 mg Capsule (Drug); MBX-8025 10 mg Capsule (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Gilead Sciences
- Primary completion
- Sep 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Relative Change From Baseline in Serum Alkaline Phosphatase (ALP) at Week 8 |
-26.06; -33.38; -41.42 | = 0.2242 |
| SECONDARY Absolute Change From Baseline in Serum Alkaline Phosphatase (ALP) at Week 12 and Week 52 |
-68.318; -135.902; -127.867; -101.150; -158.310; -133.760 | — |
| SECONDARY Change in Aspartate Aminotransferase (AST) From Baseline to 12 Weeks and 52 Weeks |
-2.50; -1.13; -3.35; -7.05; -6.18; -6.14 | — |
| SECONDARY Change in Alanine Aminotransferase (ALT) From Baseline to 12 Weeks and 52 Weeks |
-5.59; -10.48; -10.87; -14.30; -17.29; -15.32 | — |
| SECONDARY Change in Gamma-glutamyl Transferase (GGT) From Baseline to 12 Weeks and 52 Weeks |
-43.68; -75.35; -80.82; -78.60; -91.37; -88.08 | — |
| SECONDARY Change in Bilirubin - Total Bilirubin (TB) From Baseline to 12 Weeks and 52 Weeks |
-0.010; -0.055; -0.067; 0.002; -0.028; -0.068 | — |
| SECONDARY Percentage of Participants Meet Composite Endpoint Criteria of ALP and Total Bilirubin |
45.5; 48.9; 66.7; 63.6; 53.3; 67.3 | — |
| SECONDARY Percentage of Participants Meet Published PBC Response Criteria - Paris I |
81.8; 76.1; 75.5; 90; 81.0; 79.2 | — |
| SECONDARY Percentage of Participants Meet Published PBC Response Criteria - Paris II |
36.4; 37.0; 59.2; 50.0; 54.8; 60.4 | — |
| SECONDARY Percentage of Participants Meet Published PBC Response Criteria - Toronto I |
63.6; 51.1; 78.4; 63.6; 57.8; 71.4 | — |
| SECONDARY UK-PBC Risk Score Value |
1.3929; 2.2553; 1.8124; 1.3145; 2.3485; 1.7244 | — |
| SECONDARY Change From Baseline in Pruritus Visual Analog Score (VAS) at Week 12 and Week 52 |
-3.7; -5.5; -12.3; -3.3; -9.6; -16.5 | — |
| SECONDARY Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 |
1.9; -0.7; -0.5; 0.3; -1.4; -0.1 | — |
| SECONDARY Percentage of Participants Meet Published PBC Response Criteria - Barcelona |
9.1; 42.6; 62.7; 45.5; 66.7; 65.3 | — |
| SECONDARY Absolute Change in MELD Score From Baseline to 12 Weeks and 52 Weeks |
-0.3; 0.1; 0.1; -0.7; 0.3; 0.2 | — |
| SECONDARY Change in GLOBE PBC Score From Baseline to 12 Weeks and 52 Weeks |
-0.079; -0.292; -0.346; -0.180; -0.271; -0.404 | — |
| SECONDARY Participants Meet Rotterdam Criteria |
11; 38; 40; 10; 36; 42 | — |
| SECONDARY Percentage of Participants Meet Composite Endpoint of AP and Total Bilirubin Criteria at Week 12 and Week 52 |
45.5; 48.9; 66.7; 63.6; 53.3; 67.3 | — |
| SECONDARY Percent Change in Serum Alkaline Phosphatase (ALP) |
-22.56; -34.49; -43.20; -32.72; -40.09; -44.19 | — |
Summary
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)
Eligibility Criteria
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 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
- On a stable and recommended dose of UDCA for the past twelve months or intolerant to UDCA
- AP ≥ 1.67 × ULN
- 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
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)
- AST or ALT > 3 × ULN
- Total bilirubin > 2.0 mg/dL
- Total bilirubin > ULN AND albumin 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 or simvastatin
- Current use of obeticholic acid
- Use of an experimental or unapproved treatment for PBC
- Use of experimental or unapproved immunosuppressant
- Adverse event leading to MBX-8025 discontinuation from CymaBay's phase 2 PBC study (CB8025-21528)
- 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
Data sourced from ClinicalTrials.gov (NCT02955602). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.