We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 3 for:    Cymabay | PBC
Previous Study | Return to List | Next Study

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

This study is currently recruiting participants.
Verified December 2017 by CymaBay Therapeutics, Inc.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02955602
First Posted: November 4, 2016
Last Update Posted: December 7, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
CymaBay Therapeutics, Inc.
  Purpose
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)

Condition Intervention Phase
Primary Biliary Cirrhosis Drug: MBX-8025 2 mg Capsule Drug: MBX-8025 5 mg Capsule Drug: MBX-8025 10 mg Capsule Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by CymaBay Therapeutics, Inc.:

Primary Outcome Measures:
  • Serum Alkaline Phosphatase (AP) [ Time Frame: over 8 weeks ]
  • Adverse events (AE) and Treatment Emergent Adverse Events (TEAEs), ECG, biochemistry, hematology and urinalysis (NCI CTCAE Version 4.0) [ Time Frame: over 52 weeks ]

Secondary Outcome Measures:
  • Serum Alkaline Phosphatase (AP) [ Time Frame: over 8 weeks, 12 weeks, 26 weeks and 52 weeks ]
  • Aspartate Aminotransferase (AST) [ Time Frame: over 8 weeks, 12 weeks, 26 weeks and 52 weeks ]
  • Alanine Aminotransferase (ALT) [ Time Frame: over 8 weeks, 12 weeks, 26 weeks and 52 weeks ]
  • Gamma-glutamyl Transferase (GGT) [ Time Frame: over 8 weeks, 12 weeks, 26 weeks and 52 weeks ]
  • 5'nucleotidase [ Time Frame: over 8 weeks, 12 weeks, 26 weeks and 52 weeks ]
  • Bilirubin - Total Bilirubin [ Time Frame: over 8 weeks, 12 weeks, 26 weeks and 52 weeks ]
  • Bilirubin - Conjugated Bilirubin [ Time Frame: over 8 weeks, 12 weeks, 26 weeks and 52 weeks ]
  • Bilirubin - Unconjugated Bilirubin [ Time Frame: over 8 weeks, 12 weeks, 26 weeks and 52 weeks ]
  • Bone Specific Alkaline Phosphatase (AP) [ Time Frame: over 8 weeks, 12 weeks, 26 weeks and 52 weeks ]
  • Triglycerides (TG) [ Time Frame: over 8 weeks, 12 weeks, 26 weeks and 52 weeks ]
  • Total Cholesterol (TC) [ Time Frame: over 8 weeks, 12 weeks, 26 weeks and 52 weeks ]
  • High Density Lipoprotein Cholesterol (HDL-C) [ Time Frame: over 8 weeks, 12 weeks, 26 weeks and 52 weeks ]
  • Low Density Lipoprotein Cholesterol (LDL-C) [ Time Frame: over 8 weeks, 12 weeks, 26 weeks and 52 weeks ]
  • Composite Endpoint of AP and Total Bilirubin [ Time Frame: over 8 weeks, 12 weeks, 26 weeks and 52 weeks ]
    • AP < 1.67 × upper limit of normal (ULN)
    • Total Bilirubin within normal limit
    • > 15% decrease in AP

  • Published PBC Response Criteria - Paris I [ Time Frame: over 8 weeks, 12 weeks, 26 weeks and 52 weeks ]
  • Published PBC Response Criteria - Paris II [ Time Frame: over 8 weeks, 12 weeks, 26 weeks and 52 weeks ]
  • Published PBC Response Criteria - Toronto I [ Time Frame: over 8 weeks, 12 weeks, 26 weeks and 52 weeks ]
  • Published PBC Response Criteria - Toronto II [ Time Frame: over 8 weeks, 12 weeks, 26 weeks and 52 weeks ]
  • Published PBC Response Criteria - UK-PBC Risk Score [ Time Frame: over 8 weeks, 12 weeks, 26 weeks and 52 weeks ]
  • 5D-itch Scale [ Time Frame: over 8 weeks, 12 weeks, 26 weeks and 52 weeks ]
  • Pruritus Visual Analog Score (VAS) [ Time Frame: over 8 weeks, 12 weeks, 26 weeks and 52 weeks ]
  • PBC-40 Quality of Life (QoL) [ Time Frame: over 8 weeks, 12 weeks, 26 weeks and 52 weeks ]
  • PK of MBX-8025 and Metabolites [ Time Frame: (at 0, 0.5, 1, 2, 4, 6 and 24 hours for Cmax, Tmax, T1/2, AUC and trough level) ]
  • Published PBC Response Criteria - Barcelona [ Time Frame: over 8 weeks, 12 weeks, 26 weeks and 52 weeks ]

Estimated Enrollment: 116
Actual Study Start Date: November 28, 2016
Estimated Study Completion Date: January 2020
Estimated Primary Completion Date: July 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MBX-8025 (2 mg)
MBX-8025 2 mg capsule once daily
Drug: 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.

Other Names:
  • MBX-8025
  • seladelpar
Experimental: MBX-8025 (5 mg)
MBX-8025 5 mg capsule once daily
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.

Other Names:
  • MBX-8025
  • seladelpar
Experimental: MBX-8025 (10 mg)
MBX-8025 10 mg capsule once daily
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.

Other Names:
  • MBX-8025
  • seladelpar

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02955602


Contacts
Contact: Pol F Boudes, MD 510-293-8815 PBoudes@cymabay.com
Contact: Alexandra (Sasha) Steinberg, MD, PhD 510-293-8817 ASteinberg@cymabay.com

  Show 32 Study Locations
Sponsors and Collaborators
CymaBay Therapeutics, Inc.
Investigators
Study Chair: Pol F Boudes, MD CymaBay Therapeutics, Inc.
  More Information

Responsible Party: CymaBay Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02955602     History of Changes
Other Study ID Numbers: CB8025-21629
First Submitted: November 2, 2016
First Posted: November 4, 2016
Last Update Posted: December 7, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by CymaBay Therapeutics, Inc.:
PBC
Primary Biliary Cholangitis (PBC)

Additional relevant MeSH terms:
Cholangitis
Liver Cirrhosis, Biliary
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Cholestasis, Intrahepatic
Cholestasis
Liver Diseases
Liver Cirrhosis
Ursodeoxycholic Acid
Cholagogues and Choleretics
Gastrointestinal Agents