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Primary Biliary CirrhosisPhase 2NCT02955602

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

A Phase 2 study testing MBX-8025 2 mg Capsule, MBX-8025 5 mg Capsule and MBX-8025 10 mg Capsule in people with Primary Biliary Cirrhosis, run by Gilead Sciences at 38 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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) Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Primary Biliary Cirrhosis
What is being tested?
MBX-8025 2 mg Capsule, MBX-8025 5 mg Capsule and MBX-8025 10 mg Capsule
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
119 participants
Where
38 sitesin 4 countries
Study dates
28 Nov 2016to 8 Jul 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 9Show fewer
  • 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

Who cannot join

  • 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
Show all 18Show fewer
  • 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

Trial locations and contacts

38 sites in 4 countries.

38 sites in 4 countries

United States23 sites

  • Atlanta Gastroenterology Associates, LLC

    Atlanta, Georgia, 30308

  • Digestive Healthcare of Georgia

    Atlanta, Georgia, 30309

  • Mercy Medical Center

    Baltimore, Maryland, 21202

  • Northest Clinical Research Center, LLC.

    Bethlehem, Pennsylvania, 18017

  • Institute for Liver Health

    Chandler, Arizona, 85224

  • Northwestern University

    Chicago, Illinois, 60611

  • Southern California Research Center

    Coronado, California, 92118

  • UT Southwestern Medical Center Investigation Drug Service

    Dallas, Texas, 75390

  • Baylor College of Medicine

    Houston, Texas, 77030

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Florida Research Institute

    Lakewood Rch, Florida, 34211

  • Gastroenterology Consultants of SA

    Live Oak, Texas, 78233

  • Northwell Health - Center for Liver Disease and Transplantation

    Manhasset, New York, 11030

  • University of Miami - Center for Liver Diseases

    Miami, Florida, 33136

  • NYU Langone Medical Center

    New York, New York, 10016

  • The Mount Sinai Medical Center

    New York, New York, 10029

  • Bon Secours St. Mary's Immaculate Hospital

    Newport News, Virginia, 23602

  • Henry Ford Health System

    Novi, Michigan, 48377

  • Standford University Medicine

    Palo Alto, California, 94305

  • University of California, Davis Medical Center

    Sacramento, California, 95817

  • University of Washington

    Seattle, Washington, 98104

  • Saint Louis University, Gastroenterology & Hepatology

    St Louis, Missouri, 63104

  • Ventura Clinical Trials

    Ventura, California, 93003

Other trials in United States

Germany7 sites

  • Outpatient Clinic of Internal Medicine

    Berlin, 10117

  • University Hospital Erlangen

    Erlangen, 91054

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

    Hamburg, 20099

  • Center of Internal Medicine - Medical School of Hannover

    Hanover, 30625

  • University Medical Centre of the Johannes Guttenberg-University

    Mainz, 55131

  • Universitatsklinikum Giessen und Marburg GmbH

    Marburg, 35043

  • Medizinische Universitatsklinik Tubingen

    Tübingen, 72076

Other trials in Germany

United Kingdom6 sites

  • University Hospitals Birmingham

    Birmingham, B15 2GW

  • Cambridge University Hospitals NHS Foundation Trust

    Cambridge, CB2 0QQ

  • Hull and East Yorkshire Hospitals NHS Trust

    Hull, HU3 2JZ

  • Royal Free London NHS Foundation Trust

    London, NW3 2QR

  • Plymouth Hospitals NHS Trust

    Plymouth, PL6 8DH

  • Portsmouth Hospitals NHS Trust

    Portsmouth, PO6 3LY

Other trials in United Kingdom

Canada2 sites

  • University of Calgary Liver Unit

    Calgary, Alberta, T2N 4Z6

  • Toronto Centre for Liver Disease

    Toronto, Ontario, M5G 2C4

Other trials in Canada

About this study

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)

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)

Read the 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

Being tested
MBX-8025 2 mg Capsule, MBX-8025 5 mg Capsule, MBX-8025 10 mg Capsule
Keywords
PBC, Primary Biliary Cholangitis (PBC)
Medical subject headings
Liver Cirrhosis, Biliary

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MBX-8025 2 mg CapsuleDrug

    Also called MBX-8025, seladelpar

    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 CapsuleDrug

    Also called MBX-8025, seladelpar

    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 CapsuleDrug

    Also called MBX-8025, seladelpar

    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.

Study groups in NCT02955602
Study groupRoleWhat they receive
MBX-8025 (2 mg)ExperimentalMBX-8025 2 mg capsule once daily
Receives: Drug: MBX-8025 2 mg Capsule
MBX-8025 (5 mg)ExperimentalMBX-8025 5 mg capsule once daily
Receives: Drug: MBX-8025 5 mg Capsule
MBX-8025 (10 mg)ExperimentalMBX-8025 10 mg capsule once daily
Receives: Drug: MBX-8025 10 mg Capsule

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 8 weeks

Secondary outcomes (18)

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

    Absolute change in ALP from baseline to Weeks 12 and 52 The 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.

    Measured: 12 weeks and 52 weeks

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

    Change from baseline in AST levels at endpoint was reported. The 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.

    Measured: 12 weeks and 52 weeks

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

    Change from baseline in ALT levels at endpoint was reported. The 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.

    Measured: 12 weeks and 52 weeks

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

    Change from baseline in GGT levels at endpoint was reported. The 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.

    Measured: 12 weeks and 52 weeks

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

    Change from baseline in TB levels at endpoint is being reported. The 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.

    Measured: 12 weeks and 52 weeks

  6. Percentage of Participants Meet Composite Endpoint Criteria of ALP and Total Bilirubin

    Participant meets composite endpoint is defined by participant meets all of the following criteria:

    • ALP < 1.67 × upper limit of normal (ULN)
    • Total Bilirubin within normal limit
    • > 15% decrease in ALP

    Endpoint of Alkaline Phosphatase and Total Bilirubin by Visit (mITT Population)

    Measured: 12 Weeks and 52 Weeks

  7. Percentage of Participants Meet Published PBC Response Criteria - Paris I

    Percentage of participants with response based on Paris I risk score was defined as ALP less than or equal to (≤) 3x ULN and aspartate aminotransferase (AST) less than or equal to (≤) 2 x ULN and Total Bilirubin ≤ 1 mg/dL.

    The 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.

    Measured: 12 weeks and 52 weeks

  8. Percentage of Participants Meet Published PBC Response Criteria - Paris II

    Percentage of participants with response based on Paris II risk score was defined as ALP≤1.5xULN and AST≤1.5xULN and Total Bilirubin ≤ 1 mg/dL.

    The 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.

    Measured: 12 weeks and 52 weeks

  9. Percentage of Participants Meet Published PBC Response Criteria - Toronto I

    Percentage of participants with response based on Toronto I risk score defined as ALP ≤ 1.67 x ULN. The 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.

    Measured: 12 weeks and 52 weeks

  10. UK-PBC Risk Score Value

    The UK-PBC Risk Score at endpoint is defined by the mean percentage risk that a PBC patient treated with ursodeoxycholic acid (UDCA) would develop liver failure requiring liver transplantation in 5, 10 and 15 years from diagnosis. The higher the score might indicate higher risk to death or live transplantation. Formula used for UK-PBC risk score = 1- 0.982 ^EXP(0.0287854*(ALP12 x ULN-1.722136304) - 0.0422873*(((TA12 xULN/10)^-1) - 8.675729006) + 1.4199 * (LN(BIL12 x ULN/10)+2.709607778)-1.960303*(Albumin x LLN-1.17673001)-0.4161954*(Platelet x LLN-1.873564875)). Where, Baseline survivor function = 0.982, 0.941, and 0.893 for 5 years, 10 years and 15 years respectively. ALP12, TA12 and BIL12 refers to the ALP, transaminases (ALT, AST), and total bilirubin assessments, respectively. 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.

    Measured: 12 weeks and 52 weeks

  11. Change From Baseline in Pruritus Visual Analog Score (VAS) at Week 12 and Week 52

    VAS is the commonly used graphic tool for self-reporting of pruritus intensity in patients. VAS is a simple to use, validated, reliable and widely applicable tool that does not determine the impact of pruritus to quality of life. It comprises of a 100-mm horizontal line labelled as "no symptom" on left end and "worst imaginable symptom" on right end. Based on the intensity of the itch patient is instructed to draw a vertical line on the horizontal scale having a range [VAS values (unit: mm) ranging from 0 to 100, where 0 represents "no itching" and 100 "worst possible itching"].

    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.

    Measured: 12 weeks and 52 weeks

  12. Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52

    The PBC-40 QoL questionnaire is a disease-specific health-related tool developed for measuring the psychometric profile in PBC patients. It has 10 domains and 43 questions relevant to PBC, including Cognitive, Social, Emotional Function, Fatigue, Itch, and Other Symptoms. Questions in domains: 1) digestion and diet (questions 1-3); 2) experiences (questions 4-7); 3) itching (questions 8-10); 4) fatigue (questions 11-18); 5) effort and planning (questions 19-21); 6) memory and concentration (questions 22-27); 7) affects to you as person (questions 28-33); 8) affects to your social life (questions 34-37); 9) overall impact on your life (questions 38-40); 10) general health and well-being (questions A-C). Within a domain, items are scored from 1 to 5 and the individual item scores are summed to give a total domain score. High scores represent high impact and low scores low impact of PBC on QoL (mITT Population).

    Measured: 12 weeks and 52 weeks

  13. Percentage of Participants Meet Published PBC Response Criteria - Barcelona

    Percentage of participants with response based on Barcelona risk scores was defined as Normalization of ALP or a Decrease of ALP ≥ 40%. The 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.

    Measured: 12 weeks and 52 weeks

  14. Absolute Change in MELD Score From Baseline to 12 Weeks and 52 Weeks

    Change from baseline to 12 weeks and 52 weeks in Model for End-stage Liver Disease (MELD) Score (mITT Population) The MELD score ranges from 6 to 40 and is a measure of how severe a patient's liver disease is. The higher the score, the more likely the patients will need a liver transplant. A calculated prognostic risk factor used to assess the potential need for a liver transplant.

    MELD(i) score = 10*[0.957*ln(creatinine mg/dL) + 0. 378*ln(total bilirubin mg/dL) + 1.120*ln (INR) + 0.643].

    If MELD(i) is less than or equal to 11 then MELD = MELD(i). If MELD(i) is greater than 11 then MELD = MELD(i) + (1.32 *(137 - (Na)) - (0.033*MELD(i)*(137 - Na))

    Measured: 12 weeks and 52 weeks

  15. Change in GLOBE PBC Score From Baseline to 12 Weeks and 52 Weeks

    Change from Baseline to 12 weeks and 52 weeks in Global PBC Study Group (GLOBE) score (mITT Population)

    The GLOBE score is a validated risk assessment tool providing an estimate of transplant-free survival for patients with PBC. It was developed by the Global PBC Study Group using Cox regression model on over 4,000 patients with PBC. Lower GLOBE score predicts lower risk. It is calculated from the following equation:

    GLOBE score = (0.044378 * age + 0.93982 * LN(total bilirubin/ULN) +(0.335648 * LN(alkaline phosphatase/ULN)) - 2.266708 * albumin /LLN -0.002581 * platelet count per 109/L) + 1.216865

    Measured: 12 weeks and 52 weeks

  16. Participants Meet Rotterdam Criteria

    participants with Response Based on Rotterdam Criteria at Weeks 12 and 52 Rotterdam Published PBC Response Criteria by Visit (mITT Population) Rotterdam criteria: Early (normal total bilirubin and normal albumin), Moderately advanced (either abnormal albumin or abnormal total bilirubin), and Advanced (both abnormal albumin and abnormal total bilirubin). From Early stage to Moderate Stage and to Advanced Stage, it becomes worse and worse in abnormality.

    Measured: 12 weeks and 52 weeks

  17. Percentage of Participants Meet Composite Endpoint of AP and Total Bilirubin Criteria at Week 12 and Week 52

    Percentage of participants with Response Defined by Composite Endpoint (ALP< 1.67 * Upper Limit of Normal [ULN] at Endpoint, Total Bilirubin [BIL] within Normal Limits at Endpoint, and Greater Than Equal To [≥] 15% ALP Reduction) from Baseline to Week 12 and Week 52 The 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.

    Measured: 12 weeks and 52 weeks

  18. Percent Change in Serum Alkaline Phosphatase (ALP)

    Percent change in ALP from baseline to Weeks 12 and 52 The 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.

    Measured: 12 weeks and 52 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Nov 2016 (estimated)
  2. Study start28 Nov 2016
  3. Primary completion7 Sep 2018
  4. Study completion8 Jul 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
119 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02955602
Sponsor's protocol ID
CB8025-21629
Status last verified
Jun 2022
First submitted
2 Nov 2016
Last updated
14 Jul 2022
Individual data sharing
No

Publications

  • 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.

    PubMed 35367282

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing MBX-8025 2 mg Capsule, MBX-8025 5 mg Capsule and MBX-8025 10 mg Capsule in people with Primary Biliary Cirrhosis, run by Gilead Sciences at 38 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 38 sites in United States, Germany, United Kingdom, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Jul 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Relative Change From Baseline in Serum Alkaline Phosphatase (ALP) at Week 8 (time frame: 8 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02955602, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2022.

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