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

NCT ID: NCT02955602

Last Updated: 2022-07-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 119 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-28
• Study Completion Date: 2019-07-08

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

Conditions

Primary Biliary Cirrhosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MBX-8025 (2 mg)

MBX-8025 2 mg capsule once daily

Group Type: EXPERIMENTAL

MBX-8025 2 mg Capsule

Intervention Type: 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.

MBX-8025 (5 mg)

MBX-8025 5 mg capsule once daily

Group Type: EXPERIMENTAL

MBX-8025 5 mg Capsule

Intervention Type: 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.

MBX-8025 (10 mg)

MBX-8025 10 mg capsule once daily

Group Type: EXPERIMENTAL

MBX-8025 10 mg Capsule

Intervention Type: 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.

Interventions

MBX-8025 2 mg Capsule

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.

Intervention Type: DRUG

MBX-8025 5 mg Capsule

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.

Intervention Type: DRUG

MBX-8025 10 mg Capsule

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.

Intervention Type: DRUG

Other Intervention Names

MBX-8025; seladelpar; MBX-8025; seladelpar; MBX-8025; seladelpar

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Institute for Liver Health

Chandler, Arizona, United States

Southern California Research Center

Coronado, California, United States

Standford University Medicine

Palo Alto, California, United States

University of California, Davis Medical Center

Sacramento, California, United States

Ventura Clinical Trials

Ventura, California, United States

Florida Research Institute

Lakewood Rch, Florida, United States

University of Miami - Center for Liver Diseases

Miami, Florida, United States

Atlanta Gastroenterology Associates, LLC

Atlanta, Georgia, United States

Digestive Healthcare of Georgia

Atlanta, Georgia, United States

Northwestern University

Chicago, Illinois, United States

Mercy Medical Center

Baltimore, Maryland, United States

Henry Ford Health System

Novi, Michigan, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

Saint Louis University, Gastroenterology & Hepatology

St Louis, Missouri, United States

Northwell Health - Center for Liver Disease and Transplantation

Manhasset, New York, United States

NYU Langone Medical Center

New York, New York, United States

The Mount Sinai Medical Center

New York, New York, United States

Northest Clinical Research Center, LLC.

Bethlehem, Pennsylvania, United States

UT Southwestern Medical Center Investigation Drug Service

Dallas, Texas, United States

Baylor College of Medicine

Houston, Texas, United States

Gastroenterology Consultants of SA

Live Oak, Texas, United States

Bon Secours St. Mary's Immaculate Hospital

Newport News, Virginia, United States

University of Washington

Seattle, Washington, United States

University of Calgary Liver Unit

Calgary, Alberta, Canada

Toronto Centre for Liver Disease

Toronto, Ontario, Canada

Outpatient Clinic of Internal Medicine

Berlin, , Germany

University Hospital Erlangen

Erlangen, , Germany

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

Hamburg, , Germany

Center of Internal Medicine - Medical School of Hannover

Hanover, , Germany

University Medical Centre of the Johannes Guttenberg-University

Mainz, , Germany

Universitatsklinikum Giessen und Marburg GmbH

Marburg, , Germany

Medizinische Universitatsklinik Tubingen

Tübingen, , Germany

University Hospitals Birmingham

Birmingham, , United Kingdom

Cambridge University Hospitals NHS Foundation Trust

Cambridge, , United Kingdom

Hull and East Yorkshire Hospitals NHS Trust

Hull, , United Kingdom

Royal Free London NHS Foundation Trust

London, , United Kingdom

Plymouth Hospitals NHS Trust

Plymouth, , United Kingdom

Portsmouth Hospitals NHS Trust

Portsmouth, , United Kingdom

Countries

United States; Canada; Germany; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 35367282 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CB8025-21629

Identifier Type: -

Identifier Source: org_study_id