Seladelpar (MBX-8025) in Subjects With Primary Biliary Cholangitis (PBC)

NCT02955602 | Completed Phase 2 Results

• 1 other identifier: CB8025-21629
• Study Type: interventional
• Target: 119
• Locations: 4 countries
• Sites: 38

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)

Conditions

Primary Biliary Cirrhosis

Keywords

PBC; Primary Biliary Cholangitis (PBC)

Outcome Measures

Primary Outcomes (1)

• Relative Change From Baseline in Serum Alkaline Phosphatase (ALP) at Week 8

  Relative change from baseline in serum ALP levels at Week 8 (endpoint). The modified Intent-to-Treat (mITT) analysis set included all randomized subjects with confirmed PBC who received at least one study drug dose and had at least one post baseline ALP evaluation on treatment. n, denotes number of subjects evaluable for the respective timepoints

  8 weeks

Secondary Outcomes (18)

• Absolute Change From Baseline in Serum Alkaline Phosphatase (ALP) at Week 12 and Week 52

  12 weeks and 52 weeks

• Change in Aspartate Aminotransferase (AST) From Baseline to 12 Weeks and 52 Weeks

  12 weeks and 52 weeks

• Change in Alanine Aminotransferase (ALT) From Baseline to 12 Weeks and 52 Weeks

  12 weeks and 52 weeks

• Change in Gamma-glutamyl Transferase (GGT) From Baseline to 12 Weeks and 52 Weeks

  12 weeks and 52 weeks

• Change in Bilirubin - Total Bilirubin (TB) From Baseline to 12 Weeks and 52 Weeks

  12 weeks and 52 weeks

Study Arms (3)

MBX-8025 (2 mg)

EXPERIMENTAL

MBX-8025 2 mg capsule once daily

Drug: MBX-8025 2 mg Capsule

MBX-8025 (5 mg)

EXPERIMENTAL

MBX-8025 5 mg capsule once daily

Drug: MBX-8025 5 mg Capsule

MBX-8025 (10 mg)

EXPERIMENTAL

MBX-8025 10 mg capsule once daily

Drug: MBX-8025 10 mg Capsule

Interventions

MBX-8025 2 mg Capsule DRUG

Initial 8-week treatment: • MBX-8025 2 mg Extension: The 2 mg group will be started after safety and efficacy review of the 5 mg and the 10 mg groups has been completed. Subjects will initially enter the extension on their assigned dose. The dose might be up- or down-titrated after safety and efficacy data review of the first 8 weeks of treatment. During the extension, a subject's dose might be re-adjusted for safety or efficacy reasons.

Also known as: MBX-8025, seladelpar

MBX-8025 (2 mg)

MBX-8025 5 mg Capsule DRUG

Initial 8-week treatment: • MBX-8025 5 mg Extension: Subjects will initially enter the extension on their assigned dose. The dose might be up- or down-titrated after safety and efficacy data review of the first 8 weeks of treatment. During the extension, a subject's dose might be re-adjusted for safety or efficacy reasons.

Also known as: MBX-8025, seladelpar

MBX-8025 (5 mg)

MBX-8025 10 mg Capsule DRUG

Initial 8-week treatment: • MBX-8025 10 mg Extension: Subjects will initially enter the extension on their assigned dose. The dose might be up- or down-titrated after safety and efficacy data review of the first 8 weeks of treatment. During the extension, a subject's dose might be re-adjusted for safety or efficacy reasons.

Also known as: MBX-8025, seladelpar

MBX-8025 (10 mg)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have given written informed consent (signed and dated) and any authorizations required by local law
• 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

You may not qualify if:

• 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 \< LLN with the exception to subjects with Gilbert's Syndrome. Subjects with Gilbert's syndrome are excluded if Direct Bilirubin \> 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (38)

Institute for Liver Health

Chandler, Arizona, 85224, United States

Location

Southern California Research Center

Coronado, California, 92118, United States

Location

Standford University Medicine

Palo Alto, California, 94305, United States

Location

University of California, Davis Medical Center

Sacramento, California, 95817, United States

Location

Ventura Clinical Trials

Ventura, California, 93003, United States

Location

Florida Research Institute

Lakewood Rch, Florida, 34211, United States

Location

University of Miami - Center for Liver Diseases

Miami, Florida, 33136, United States

Location

Atlanta Gastroenterology Associates, LLC

Atlanta, Georgia, 30308, United States

Location

Digestive Healthcare of Georgia

Atlanta, Georgia, 30309, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Mercy Medical Center

Baltimore, Maryland, 21202, United States

Location

Henry Ford Health System

Novi, Michigan, 48377, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Saint Louis University, Gastroenterology & Hepatology

St Louis, Missouri, 63104, United States

Location

Northwell Health - Center for Liver Disease and Transplantation

Manhasset, New York, 11030, United States

Location

NYU Langone Medical Center

New York, New York, 10016, United States

Location

The Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Northest Clinical Research Center, LLC.

Bethlehem, Pennsylvania, 18017, United States

Location

UT Southwestern Medical Center Investigation Drug Service

Dallas, Texas, 75390, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Gastroenterology Consultants of SA

Live Oak, Texas, 78233, United States

Location

Bon Secours St. Mary's Immaculate Hospital

Newport News, Virginia, 23602, United States

Location

University of Washington

Seattle, Washington, 98104, United States

Location

University of Calgary Liver Unit

Calgary, Alberta, T2N 4Z6, Canada

Location

Toronto Centre for Liver Disease

Toronto, Ontario, M5G 2C4, Canada

Location

Outpatient Clinic of Internal Medicine

Berlin, 10117, Germany

Location

University Hospital Erlangen

Erlangen, 91054, Germany

Location

Ifi-Studien und Projekte GmbH, An der Asklepios Klinik St. Georg

Hamburg, 20099, Germany

Location

Center of Internal Medicine - Medical School of Hannover

Hanover, 30625, Germany

Location

University Medical Centre of the Johannes Guttenberg-University

Mainz, 55131, Germany

Location

Universitatsklinikum Giessen und Marburg GmbH

Marburg, 35043, Germany

Location

Medizinische Universitatsklinik Tubingen

Tübingen, 72076, Germany

Location

University Hospitals Birmingham

Birmingham, B15 2GW, United Kingdom

Location

Cambridge University Hospitals NHS Foundation Trust

Cambridge, CB2 0QQ, United Kingdom

Location

Hull and East Yorkshire Hospitals NHS Trust

Hull, HU3 2JZ, United Kingdom

Location

Royal Free London NHS Foundation Trust

London, NW3 2QR, United Kingdom

Location

Plymouth Hospitals NHS Trust

Plymouth, PL6 8DH, United Kingdom

Location

Portsmouth Hospitals NHS Trust

Portsmouth, PO6 3LY, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 35367282 DERIVED

MeSH Terms

Conditions

Liver Cirrhosis, Biliary

Interventions

(2-methyl-4-(5-methyl-2-(4-trifluoromethyl-phenyl)-2H-(1,2,3)triazol-4-ylmethylsulfanyl)phenoxy)acetic acid; seladelpar

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

First, there was an imbalance in baseline ALP levels among cohorts. Second, the criteria for dose uptitration were not standardized, except that uptitration could only be done at or after Week 12. Third, this was not a placebo-controlled study. Finally, multiplicity adjustments were not made for efficacy endpoints. Nominal p-values were provided for descriptive purposes.

Results Point of Contact

• Title: Elaine Watkins, DO, MSPH, Vice President of Clinical Development
• Organization: CymaBay Therapeutics, Inc.

medinfo@cymabay.com

510-293-8800

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2016
• First Posted: November 4, 2016
• Study Start: November 28, 2016
• Primary Completion: September 7, 2018
• Study Completion: July 8, 2019
• Last Updated: July 14, 2022
• Results First Posted: July 14, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (23); CA (2); DE (7); GB (6)