Clinical trial NCT02955602: Seladelpar (MBX-8025) in Subjects With Primary Biliary Cholangitis (PBC)
Official 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Biliary Cirrhosis
Keywords: PBC
Primary Biliary Cholangitis (PBC)
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2016-11-04
Enrollment: 119
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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)

Detailed description: Primary:

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

Secondary:

To evaluate the safety and efficacy of MBX-8025 2 mg, 5 mg, and 10 mg over 12 and 26 weeks of treatment

To evaluate the safety and efficacy of MBX-8025 2 mg, 5 mg, and 10 mg over 52 weeks of treatment

To evaluate the pharmacokinetics (PK) of MBX-8025

Exploratory:

To evaluate the effect of MBX-8025 on bile acids, additional markers of inflammation and renal function

MBX-8025 doses of 1 mg and 15 mg may be evaluated if dose adjustment occurs

Eligibility 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

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 \> 2.0 mg/dL
4. Total bilirubin \> ULN AND albumin \< LLN with the exception to subjects with Gilbert's Syndrome. Subjects with Gilbert's syndrome are excluded if Direct Bilirubin \> ULN.
5. Auto-immune hepatitis
6. Primary sclerosing cholangitis
7. Known history of alpha-1-Antitrypsin deficiency
8. Known history of chronic viral hepatitis
9. Creatine kinase above ULN
10. Serum creatinine above ULN
11. For females, pregnancy or breast-feeding
12. Use of colchicine, methotrexate, azathioprine, or systemic steroids in the two months preceding screening
13. Current use of fibrates or simvastatin
14. Current use of obeticholic acid
15. Use of an experimental or unapproved treatment for PBC
16. Use of experimental or unapproved immunosuppressant
17. Adverse event leading to MBX-8025 discontinuation from CymaBay's phase 2 PBC study (CB8025-21528)
18. 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

Primary outcomes:
measure: Relative Change From Baseline in Serum Alkaline Phosphatase (ALP) at Week 8
timeFrame: 8 weeks
Secondary outcomes:
measure: Absolute Change From Baseline in Serum Alkaline Phosphatase (ALP) at Week 12 and Week 52
timeFrame: 12 weeks and 52 weeks
measure: Change in Aspartate Aminotransferase (AST) From Baseline to 12 Weeks and 52 Weeks
timeFrame: 12 weeks and 52 weeks
measure: Change in Alanine Aminotransferase (ALT) From Baseline to 12 Weeks and 52 Weeks
timeFrame: 12 weeks and 52 weeks
measure: Change in Gamma-glutamyl Transferase (GGT) From Baseline to 12 Weeks and 52 Weeks
timeFrame: 12 weeks and 52 weeks
measure: Change in Bilirubin - Total Bilirubin (TB) From Baseline to 12 Weeks and 52 Weeks
timeFrame: 12 weeks and 52 weeks
measure: Percentage of Participants Meet Composite Endpoint Criteria of ALP and Total Bilirubin
timeFrame: 12 Weeks and 52 Weeks
measure: Percentage of Participants Meet Published PBC Response Criteria - Paris I
timeFrame: 12 weeks and 52 weeks
measure: Percentage of Participants Meet Published PBC Response Criteria - Paris II
timeFrame: 12 weeks and 52 weeks
measure: Percentage of Participants Meet Published PBC Response Criteria - Toronto I
timeFrame: 12 weeks and 52 weeks
measure: UK-PBC Risk Score Value
timeFrame: 12 weeks and 52 weeks
measure: Change From Baseline in Pruritus Visual Analog Score (VAS) at Week 12 and Week 52
timeFrame: 12 weeks and 52 weeks
measure: Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52
timeFrame: 12 weeks and 52 weeks
measure: Percentage of Participants Meet Published PBC Response Criteria - Barcelona
timeFrame: 12 weeks and 52 weeks
measure: Absolute Change in MELD Score From Baseline to 12 Weeks and 52 Weeks
timeFrame: 12 weeks and 52 weeks
measure: Change in GLOBE PBC Score From Baseline to 12 Weeks and 52 Weeks
timeFrame: 12 weeks and 52 weeks
measure: Participants Meet Rotterdam Criteria
timeFrame: 12 weeks and 52 weeks
measure: Percentage of Participants Meet Composite Endpoint of AP and Total Bilirubin Criteria at Week 12 and Week 52
timeFrame: 12 weeks and 52 weeks
measure: Percent Change in Serum Alkaline Phosphatase (ALP)
timeFrame: 12 weeks and 52 weeks
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Institute for Liver Health
state: Arizona
city: Coronado
country: United States
facility: Southern California Research Center
state: California
city: Palo Alto
country: United States
facility: Standford University Medicine
state: California
city: Sacramento
country: United States
facility: University of California, Davis Medical Center
state: California
city: Ventura
country: United States
facility: Ventura Clinical Trials
state: California
city: Lakewood Ranch
country: United States
facility: Florida Research Institute
state: Florida
city: Miami
country: United States
facility: University of Miami - Center for Liver Diseases
state: Florida
city: Atlanta
country: United States
facility: Atlanta Gastroenterology Associates, LLC
state: Georgia
city: Atlanta
country: United States
facility: Digestive Healthcare of Georgia
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Baltimore
country: United States
facility: Mercy Medical Center
state: Maryland
city: Novi
country: United States
facility: Henry Ford Health System
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Saint Louis
country: United States
facility: Saint Louis University, Gastroenterology & Hepatology
state: Missouri
city: Manhasset
country: United States
facility: Northwell Health - Center for Liver Disease and Transplantation
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: New York
country: United States
facility: The Mount Sinai Medical Center
state: New York
city: Bethlehem
country: United States
facility: Northest Clinical Research Center, LLC.
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern Medical Center Investigation Drug Service
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Live Oak
country: United States
facility: Gastroenterology Consultants of SA
state: Texas
city: Newport News
country: United States
facility: Bon Secours St. Mary's Immaculate Hospital
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Calgary
country: Canada
facility: University of Calgary Liver Unit
state: Alberta
city: Toronto
country: Canada
facility: Toronto Centre for Liver Disease
state: Ontario
city: Berlin
country: Germany
facility: Outpatient Clinic of Internal Medicine
city: Erlangen
country: Germany
facility: University Hospital Erlangen
city: Hamburg
country: Germany
facility: Ifi-Studien und Projekte GmbH, An der Asklepios Klinik St. Georg
city: Hannover
country: Germany
facility: Center of Internal Medicine - Medical School of Hannover
city: Mainz
country: Germany
facility: University Medical Centre of the Johannes Guttenberg-University
city: Marburg
country: Germany
facility: Universitatsklinikum Giessen und Marburg GmbH
city: Tubingen
country: Germany
facility: Medizinische Universitatsklinik Tubingen
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
city: Hull
country: United Kingdom
facility: Hull and East Yorkshire Hospitals NHS Trust
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust
city: Plymouth
country: United Kingdom
facility: Plymouth Hospitals NHS Trust
city: Portsmouth
country: United Kingdom
facility: Portsmouth Hospitals NHS Trust
Study officials:
References:
citation: Bowlus CL, Galambos MR, Aspinall RJ, Hirschfield GM, Jones DEJ, Dorffel Y, Gordon SC, Harrison SA, Kremer AE, Mayo MJ, Thuluvath PJ, Levy C, Swain MG, Neff GW, Sheridan DA, Stanca CM, Berg CP, Goel A, Shiffman ML, Vierling JM, Boudes P, Steinberg A, Choi YJ, McWherter CA. A phase II, randomized, open-label, 52-week study of seladelpar in patients with primary biliary cholangitis. J Hepatol. 2022 Aug;77(2):353-364. doi: 10.1016/j.jhep.2022.02.033. Epub 2022 Mar 30.