Primary Biliary Cirrhosis
Conditions
Keywords
PBC, Primary Biliary Cholangitis (PBC)
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
Interventions
DRUGMBX-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.
DRUGMBX-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.
DRUGMBX-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.
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relative Change From Baseline in Serum Alkaline Phosphatase (ALP) at Week 8 | 8 weeks | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Aspartate Aminotransferase (AST) From Baseline to 12 Weeks and 52 Weeks | 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. |
| Change in Alanine Aminotransferase (ALT) From Baseline to 12 Weeks and 52 Weeks | 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. |
| Change in Gamma-glutamyl Transferase (GGT) From Baseline to 12 Weeks and 52 Weeks | 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. |
| Change in Bilirubin - Total Bilirubin (TB) From Baseline to 12 Weeks and 52 Weeks | 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. |
| Percentage of Participants Meet Composite Endpoint Criteria of ALP and Total Bilirubin | 12 Weeks and 52 Weeks | 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) |
| Percentage of Participants Meet Published PBC Response Criteria - Paris I | 12 weeks and 52 weeks | 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. |
| Percentage of Participants Meet Published PBC Response Criteria - Paris II | 12 weeks and 52 weeks | 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. |
| Percentage of Participants Meet Published PBC Response Criteria - Toronto I | 12 weeks and 52 weeks | 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. |
| Absolute Change From Baseline in Serum Alkaline Phosphatase (ALP) at Week 12 and Week 52 | 12 weeks and 52 weeks | 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. |
| Change From Baseline in Pruritus Visual Analog Score (VAS) at Week 12 and Week 52 | 12 weeks and 52 weeks | 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. |
| Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | 12 weeks and 52 weeks | 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). |
| Percentage of Participants Meet Published PBC Response Criteria - Barcelona | 12 weeks and 52 weeks | 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. |
| Absolute Change in MELD Score From Baseline to 12 Weeks and 52 Weeks | 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)) |
| Change in GLOBE PBC Score From Baseline to 12 Weeks and 52 Weeks | 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 |
| Participants Meet Rotterdam Criteria | 12 weeks and 52 weeks | 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. |
| Percentage of Participants Meet Composite Endpoint of AP and Total Bilirubin Criteria at Week 12 and Week 52 | 12 weeks and 52 weeks | 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. |
| Percent Change in Serum Alkaline Phosphatase (ALP) | 12 weeks and 52 weeks | 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. |
| UK-PBC Risk Score Value | 12 weeks and 52 weeks | 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. |
Countries
Canada, Germany, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 192 subjects were screened of which 121 subjects randomized (2 subjects were not treated) into the study and 71 were screen failures. Subjects were randomized to the 5 and 10 mg treatment groups for entry to the 8-week initial treatment period study, while those in the 2 mg treatment group entered after being sequentially assigned their dose
Participants by arm
| Arm | Count |
|---|---|
| MBX-8025 (2 mg) MBX-8025 2 mg capsule once daily
MBX-8025 2 mg Capsule: Initial 8-week treatment:
• MBX-8025 2 mg
Subjects received two seladelpar 1 milligram (mg) capsules orally once daily for 8 weeks with a 44-week extension period. Dose up-titration for efficacy reasons could be made after 12 weeks of treatment up to 10 mg. | 11 |
| MBX-8025 (5 mg) MBX-8025 5 mg capsule once daily
MBX-8025 5 mg Capsule: Initial 8-week treatment:
• MBX-8025 5 mg
Subjects were randomized to receive one seladelpar 5 mg capsule orally once daily for 8 weeks with a 44-week extension period. Dose up-titration to 10 mg for efficacy reasons could be made after 12 weeks of treatment. | 53 |
| MBX-8025 (10 mg) MBX-8025 10 mg capsule once daily
MBX-8025 10 mg Capsule: Initial 8-week treatment:
• MBX-8025 10 mg
Subjects were randomized to receive one seladelpar 10 mg capsule orally once daily for 8 weeks with a 44-week extension period. | 55 |
| Total | 119 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 3 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Other | 0 | 1 | 3 |
| Overall Study | Withdrawal of informed consent | 1 | 3 | 2 |
Baseline characteristics
| Characteristic | MBX-8025 (5 mg) | MBX-8025 (2 mg) | MBX-8025 (10 mg) | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 12 Participants | 3 Participants | 14 Participants | 29 Participants |
| Age, Categorical Between 18 and 65 years | 41 Participants | 8 Participants | 41 Participants | 90 Participants |
| Age, Continuous | 57.5 years STANDARD_DEVIATION 8.1 | 55.2 years STANDARD_DEVIATION 9.6 | 57.4 years STANDARD_DEVIATION 9.7 | 56.4 years STANDARD_DEVIATION 9.6 |
| Race/Ethnicity, Customized American Indian or Alaska native | 0 Subjects | 0 Subjects | 1 Subjects | 1 Subjects |
| Race/Ethnicity, Customized Asian | 2 Subjects | 0 Subjects | 1 Subjects | 3 Subjects |
| Race/Ethnicity, Customized Black or African-American | 1 Subjects | 0 Subjects | 3 Subjects | 4 Subjects |
| Race/Ethnicity, Customized Multiple | 0 Subjects | 0 Subjects | 1 Subjects | 1 Subjects |
| Race/Ethnicity, Customized Other | 0 Subjects | 1 Subjects | 0 Subjects | 1 Subjects |
| Race/Ethnicity, Customized White | 50 Subjects | 10 Subjects | 49 Subjects | 109 Subjects |
| Region of Enrollment Canada | 5 participants | 0 participants | 1 participants | 6 participants |
| Region of Enrollment Germany | 4 participants | 0 participants | 7 participants | 11 participants |
| Region of Enrollment United Kingdom | 5 participants | 11 participants | 4 participants | 20 participants |
| Region of Enrollment United States | 39 participants | 0 participants | 43 participants | 82 participants |
| Sex: Female, Male Female | 51 Participants | 11 Participants | 50 Participants | 112 Participants |
| Sex: Female, Male Male | 2 Participants | 0 Participants | 5 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 53 | 0 / 55 |
| other Total, other adverse events | 11 / 11 | 45 / 53 | 47 / 55 |
| serious Total, serious adverse events | 1 / 11 | 8 / 53 | 5 / 55 |
Outcome results
Primary
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
Time frame: 8 weeks
Population: mITT Population The mITT population is defined as any enrolled subject who receives at least one dose of medication and has at least one post-baseline AP evaluation and who have confirmed PBC.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MBX-8025 (2 mg) | Relative Change From Baseline in Serum Alkaline Phosphatase (ALP) at Week 8 | -26.06 percentage change from baseline | Standard Deviation 9.15 |
| MBX-8025 (5 mg) | Relative Change From Baseline in Serum Alkaline Phosphatase (ALP) at Week 8 | -33.38 percentage change from baseline | Standard Deviation 17.81 |
| MBX-8025 (10 mg) | Relative Change From Baseline in Serum Alkaline Phosphatase (ALP) at Week 8 | -41.42 percentage change from baseline | Standard Deviation 13.05 |
Comparison: The analyses will assess the change from baseline in each treatment group and will assess the hypothesis that there are no differences in the percent change in ALP serum level between seladelpar 2 mg and 5 mg treatment groups after 8 weeks of treatment.p-value: =0.2242ANCOVA
Comparison: The analyses will assess the change from baseline in each treatment group and will assess the hypothesis that there are no differences in the percent change in ALP serum level between seladelpar 2 mg and 10 mg treatment groups after 8 weeks of treatmentp-value: =0.0021ANCOVA
Comparison: The analyses will assess the change from baseline in each treatment group and will assess the hypothesis that there are no differences in the percent change in ALP serum level between seladelpar 5 mg and 10 mg treatment groups after 8 weeks of treatmentp-value: =0.0024ANCOVA
Secondary
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.
Time frame: 12 weeks and 52 weeks
Population: mITT Population: The mITT population is defined as any enrolled subject who receives at least one dose of medication and has at least one post-baseline AP evaluation and who have confirmed PBC.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MBX-8025 (2 mg) | Absolute Change From Baseline in Serum Alkaline Phosphatase (ALP) at Week 12 and Week 52 | Absolute Change at Week 12 | -68.318 U/L | Standard Deviation 63.276 |
| MBX-8025 (2 mg) | Absolute Change From Baseline in Serum Alkaline Phosphatase (ALP) at Week 12 and Week 52 | Absolute Change at Week 52 | -101.150 U/L | Standard Deviation 107.956 |
| MBX-8025 (5 mg) | Absolute Change From Baseline in Serum Alkaline Phosphatase (ALP) at Week 12 and Week 52 | Absolute Change at Week 12 | -135.902 U/L | Standard Deviation 150.954 |
| MBX-8025 (5 mg) | Absolute Change From Baseline in Serum Alkaline Phosphatase (ALP) at Week 12 and Week 52 | Absolute Change at Week 52 | -158.310 U/L | Standard Deviation 143.668 |
| MBX-8025 (10 mg) | Absolute Change From Baseline in Serum Alkaline Phosphatase (ALP) at Week 12 and Week 52 | Absolute Change at Week 12 | -127.867 U/L | Standard Deviation 60.284 |
| MBX-8025 (10 mg) | Absolute Change From Baseline in Serum Alkaline Phosphatase (ALP) at Week 12 and Week 52 | Absolute Change at Week 52 | -133.760 U/L | Standard Deviation 76.151 |
Secondary
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))
Time frame: 12 weeks and 52 weeks
Population: mITT Population. The mITT population is defined as any enrolled subject who receives at least one dose of medication and has at least one post-baseline AP evaluation and who have confirmed PBC.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MBX-8025 (2 mg) | Absolute Change in MELD Score From Baseline to 12 Weeks and 52 Weeks | Week 52 | -0.7 Change from Baseline | Standard Deviation 1.6 |
| MBX-8025 (2 mg) | Absolute Change in MELD Score From Baseline to 12 Weeks and 52 Weeks | Week 12 | -0.3 Change from Baseline | Standard Deviation 1.6 |
| MBX-8025 (5 mg) | Absolute Change in MELD Score From Baseline to 12 Weeks and 52 Weeks | Week 12 | 0.1 Change from Baseline | Standard Deviation 1.2 |
| MBX-8025 (5 mg) | Absolute Change in MELD Score From Baseline to 12 Weeks and 52 Weeks | Week 52 | 0.3 Change from Baseline | Standard Deviation 1.1 |
| MBX-8025 (10 mg) | Absolute Change in MELD Score From Baseline to 12 Weeks and 52 Weeks | Week 12 | 0.1 Change from Baseline | Standard Deviation 1 |
| MBX-8025 (10 mg) | Absolute Change in MELD Score From Baseline to 12 Weeks and 52 Weeks | Week 52 | 0.2 Change from Baseline | Standard Deviation 1.2 |
Secondary
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).
Time frame: 12 weeks and 52 weeks
Population: mITT Population. The mITT population is defined as any enrolled subject who receives at least one dose of medication and has at least one post-baseline AP evaluation and who have confirmed PBC.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MBX-8025 (2 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | General Symptoms, Week 12 | 1.9 units on a scale | Standard Deviation 2.7 |
| MBX-8025 (2 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | General Symptoms, Week 52 | 0.3 units on a scale | Standard Deviation 2.4 |
| MBX-8025 (2 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | Itch, Week 52 | 0.4 units on a scale | Standard Deviation 2.7 |
| MBX-8025 (2 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | Fatigue, Week 12 | -1.5 units on a scale | Standard Deviation 6.1 |
| MBX-8025 (2 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | Fatigue, Week 52 | -1.2 units on a scale | Standard Deviation 7.8 |
| MBX-8025 (2 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | Cognitive Function, Week 52 | -0.7 units on a scale | Standard Deviation 7.6 |
| MBX-8025 (2 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | Social, Week 52 | -3.3 units on a scale | Standard Deviation 5.2 |
| MBX-8025 (2 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | Emotional, Week 12 | -0.9 units on a scale | Standard Deviation 1.6 |
| MBX-8025 (2 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | Emotional, Week 52 | -2.1 units on a scale | Standard Deviation 2.3 |
| MBX-8025 (2 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | Itch, Week 12 | -0.4 units on a scale | Standard Deviation 2 |
| MBX-8025 (2 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | Cognitive Function, Week 12 | -0.9 units on a scale | Standard Deviation 2.4 |
| MBX-8025 (2 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | Social, Week 12 | 0.8 units on a scale | Standard Deviation 2.8 |
| MBX-8025 (5 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | Cognitive Function, Week 52 | -1.4 units on a scale | Standard Deviation 5.3 |
| MBX-8025 (5 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | General Symptoms, Week 12 | -0.7 units on a scale | Standard Deviation 5.1 |
| MBX-8025 (5 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | Cognitive Function, Week 12 | -0.6 units on a scale | Standard Deviation 5.7 |
| MBX-8025 (5 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | Fatigue, Week 12 | -2.1 units on a scale | Standard Deviation 10.4 |
| MBX-8025 (5 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | General Symptoms, Week 52 | -1.4 units on a scale | Standard Deviation 4.4 |
| MBX-8025 (5 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | Social, Week 12 | -0.5 units on a scale | Standard Deviation 7.9 |
| MBX-8025 (5 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | Emotional, Week 12 | -1.0 units on a scale | Standard Deviation 2.6 |
| MBX-8025 (5 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | Itch, Week 52 | -1.3 units on a scale | Standard Deviation 3.2 |
| MBX-8025 (5 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | Fatigue, Week 52 | -3.0 units on a scale | Standard Deviation 8.5 |
| MBX-8025 (5 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | Emotional, Week 52 | -1.3 units on a scale | Standard Deviation 2.7 |
| MBX-8025 (5 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | Social, Week 52 | -1.6 units on a scale | Standard Deviation 7.2 |
| MBX-8025 (5 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | Itch, Week 12 | -0.5 units on a scale | Standard Deviation 3.4 |
| MBX-8025 (10 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | Social, Week 52 | -1.6 units on a scale | Standard Deviation 6.2 |
| MBX-8025 (10 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | Fatigue, Week 52 | -3.4 units on a scale | Standard Deviation 6.3 |
| MBX-8025 (10 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | Cognitive Function, Week 12 | -0.7 units on a scale | Standard Deviation 2.8 |
| MBX-8025 (10 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | Cognitive Function, Week 52 | -0.6 units on a scale | Standard Deviation 2.5 |
| MBX-8025 (10 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | Social, Week 12 | -1.0 units on a scale | Standard Deviation 6.3 |
| MBX-8025 (10 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | General Symptoms, Week 52 | -0.1 units on a scale | Standard Deviation 4.4 |
| MBX-8025 (10 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | Emotional, Week 52 | -0.9 units on a scale | Standard Deviation 2.1 |
| MBX-8025 (10 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | General Symptoms, Week 12 | -0.5 units on a scale | Standard Deviation 3.6 |
| MBX-8025 (10 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | Itch, Week 12 | -0.8 units on a scale | Standard Deviation 3.1 |
| MBX-8025 (10 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | Itch, Week 52 | -1.4 units on a scale | Standard Deviation 3.7 |
| MBX-8025 (10 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | Emotional, Week 12 | -0.8 units on a scale | Standard Deviation 2.1 |
| MBX-8025 (10 mg) | Change From Baseline in PBC-40 Quality of Life (QoL) at Week 12 and Week 52 | Fatigue, Week 12 | -3.0 units on a scale | Standard Deviation 5.2 |
Secondary
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.
Time frame: 12 weeks and 52 weeks
Population: mITT Population. The mITT population is defined as any enrolled subject who receives at least one dose of medication and has at least one post-baseline AP evaluation and who have confirmed PBC.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MBX-8025 (2 mg) | Change From Baseline in Pruritus Visual Analog Score (VAS) at Week 12 and Week 52 | Week 12 | -3.7 score on a scale | Standard Deviation 6.4 |
| MBX-8025 (2 mg) | Change From Baseline in Pruritus Visual Analog Score (VAS) at Week 12 and Week 52 | Week 52 | -3.3 score on a scale | Standard Deviation 11.7 |
| MBX-8025 (5 mg) | Change From Baseline in Pruritus Visual Analog Score (VAS) at Week 12 and Week 52 | Week 12 | -5.5 score on a scale | Standard Deviation 25 |
| MBX-8025 (5 mg) | Change From Baseline in Pruritus Visual Analog Score (VAS) at Week 12 and Week 52 | Week 52 | -9.6 score on a scale | Standard Deviation 22.5 |
| MBX-8025 (10 mg) | Change From Baseline in Pruritus Visual Analog Score (VAS) at Week 12 and Week 52 | Week 12 | -12.3 score on a scale | Standard Deviation 22.3 |
| MBX-8025 (10 mg) | Change From Baseline in Pruritus Visual Analog Score (VAS) at Week 12 and Week 52 | Week 52 | -16.5 score on a scale | Standard Deviation 23 |
Secondary
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.
Time frame: 12 weeks and 52 weeks
Population: mITT Population The mITT population is defined as any enrolled subject who receives at least one dose of medication and has at least one post-baseline AP evaluation and who have confirmed PBC.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MBX-8025 (2 mg) | Change in Alanine Aminotransferase (ALT) From Baseline to 12 Weeks and 52 Weeks | Week 12 | -5.59 U/L | Standard Deviation 16.07 |
| MBX-8025 (2 mg) | Change in Alanine Aminotransferase (ALT) From Baseline to 12 Weeks and 52 Weeks | Week 52 | -14.30 U/L | Standard Deviation 25.12 |
| MBX-8025 (5 mg) | Change in Alanine Aminotransferase (ALT) From Baseline to 12 Weeks and 52 Weeks | Week 12 | -10.48 U/L | Standard Deviation 21.41 |
| MBX-8025 (5 mg) | Change in Alanine Aminotransferase (ALT) From Baseline to 12 Weeks and 52 Weeks | Week 52 | -17.29 U/L | Standard Deviation 17.46 |
| MBX-8025 (10 mg) | Change in Alanine Aminotransferase (ALT) From Baseline to 12 Weeks and 52 Weeks | Week 12 | -10.87 U/L | Standard Deviation 20.25 |
| MBX-8025 (10 mg) | Change in Alanine Aminotransferase (ALT) From Baseline to 12 Weeks and 52 Weeks | Week 52 | -15.32 U/L | Standard Deviation 13.89 |
Secondary
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.
Time frame: 12 weeks and 52 weeks
Population: mITT Population The mITT population is defined as any enrolled subject who receives at least one dose of medication and has at least one post-baseline AP evaluation and who have confirmed PBC.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MBX-8025 (2 mg) | Change in Aspartate Aminotransferase (AST) From Baseline to 12 Weeks and 52 Weeks | Week 12 | -2.50 U/L | Standard Deviation 16.72 |
| MBX-8025 (2 mg) | Change in Aspartate Aminotransferase (AST) From Baseline to 12 Weeks and 52 Weeks | Week 52 | -7.05 U/L | Standard Deviation 10.5 |
| MBX-8025 (5 mg) | Change in Aspartate Aminotransferase (AST) From Baseline to 12 Weeks and 52 Weeks | Week 12 | -1.13 U/L | Standard Deviation 24.28 |
| MBX-8025 (5 mg) | Change in Aspartate Aminotransferase (AST) From Baseline to 12 Weeks and 52 Weeks | Week 52 | -6.18 U/L | Standard Deviation 13.98 |
| MBX-8025 (10 mg) | Change in Aspartate Aminotransferase (AST) From Baseline to 12 Weeks and 52 Weeks | Week 12 | -3.35 U/L | Standard Deviation 10.55 |
| MBX-8025 (10 mg) | Change in Aspartate Aminotransferase (AST) From Baseline to 12 Weeks and 52 Weeks | Week 52 | -6.14 U/L | Standard Deviation 9.18 |
Secondary
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.
Time frame: 12 weeks and 52 weeks
Population: mITT Population The mITT population is defined as any enrolled subject who receives at least one dose of medication and has at least one post-baseline AP evaluation and who have confirmed PBC.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MBX-8025 (2 mg) | Change in Bilirubin - Total Bilirubin (TB) From Baseline to 12 Weeks and 52 Weeks | Week 12 | -0.010 mg/dL | Standard Deviation 0.121 |
| MBX-8025 (2 mg) | Change in Bilirubin - Total Bilirubin (TB) From Baseline to 12 Weeks and 52 Weeks | Week 52 | 0.002 mg/dL | Standard Deviation 0.152 |
| MBX-8025 (5 mg) | Change in Bilirubin - Total Bilirubin (TB) From Baseline to 12 Weeks and 52 Weeks | Week 12 | -0.055 mg/dL | Standard Deviation 0.161 |
| MBX-8025 (5 mg) | Change in Bilirubin - Total Bilirubin (TB) From Baseline to 12 Weeks and 52 Weeks | Week 52 | -0.028 mg/dL | Standard Deviation 0.263 |
| MBX-8025 (10 mg) | Change in Bilirubin - Total Bilirubin (TB) From Baseline to 12 Weeks and 52 Weeks | Week 52 | -0.068 mg/dL | Standard Deviation 0.19 |
| MBX-8025 (10 mg) | Change in Bilirubin - Total Bilirubin (TB) From Baseline to 12 Weeks and 52 Weeks | Week 12 | -0.067 mg/dL | Standard Deviation 0.199 |
Secondary
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.
Time frame: 12 weeks and 52 weeks
Population: mITT Population The mITT population is defined as any enrolled subject who receives at least one dose of medication and has at least one post-baseline AP evaluation and who have confirmed PBC.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MBX-8025 (2 mg) | Change in Gamma-glutamyl Transferase (GGT) From Baseline to 12 Weeks and 52 Weeks | Week 12 | -43.68 U/L | Standard Deviation 56.87 |
| MBX-8025 (2 mg) | Change in Gamma-glutamyl Transferase (GGT) From Baseline to 12 Weeks and 52 Weeks | Week 52 | -78.60 U/L | Standard Deviation 81.59 |
| MBX-8025 (5 mg) | Change in Gamma-glutamyl Transferase (GGT) From Baseline to 12 Weeks and 52 Weeks | Week 12 | -75.35 U/L | Standard Deviation 87.57 |
| MBX-8025 (5 mg) | Change in Gamma-glutamyl Transferase (GGT) From Baseline to 12 Weeks and 52 Weeks | Week 52 | -91.37 U/L | Standard Deviation 102.23 |
| MBX-8025 (10 mg) | Change in Gamma-glutamyl Transferase (GGT) From Baseline to 12 Weeks and 52 Weeks | Week 12 | -80.82 U/L | Standard Deviation 109.06 |
| MBX-8025 (10 mg) | Change in Gamma-glutamyl Transferase (GGT) From Baseline to 12 Weeks and 52 Weeks | Week 52 | -88.08 U/L | Standard Deviation 122.14 |
Secondary
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
Time frame: 12 weeks and 52 weeks
Population: mITT Population The mITT population is defined as any enrolled subject who receives at least one dose of medication and has at least one post-baseline AP evaluation and who have confirmed PBC.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MBX-8025 (2 mg) | Change in GLOBE PBC Score From Baseline to 12 Weeks and 52 Weeks | Week 52 | -0.180 units on a scale | Standard Deviation 0.217 |
| MBX-8025 (2 mg) | Change in GLOBE PBC Score From Baseline to 12 Weeks and 52 Weeks | Week 12 | -0.079 units on a scale | Standard Deviation 0.26 |
| MBX-8025 (5 mg) | Change in GLOBE PBC Score From Baseline to 12 Weeks and 52 Weeks | Week 12 | -0.292 units on a scale | Standard Deviation 0.304 |
| MBX-8025 (5 mg) | Change in GLOBE PBC Score From Baseline to 12 Weeks and 52 Weeks | Week 52 | -0.271 units on a scale | Standard Deviation 0.354 |
| MBX-8025 (10 mg) | Change in GLOBE PBC Score From Baseline to 12 Weeks and 52 Weeks | Week 12 | -0.346 units on a scale | Standard Deviation 0.269 |
| MBX-8025 (10 mg) | Change in GLOBE PBC Score From Baseline to 12 Weeks and 52 Weeks | Week 52 | -0.404 units on a scale | Standard Deviation 0.298 |
Secondary
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.
Time frame: 12 weeks and 52 weeks
Population: mITT Population. The mITT population is defined as any enrolled subject who receives at least one dose of medication and has at least one post-baseline AP evaluation and who have confirmed PBC.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MBX-8025 (2 mg) | Participants Meet Rotterdam Criteria | Early Stage,12 Weeks | 11 participants |
| MBX-8025 (2 mg) | Participants Meet Rotterdam Criteria | Early Stage, 52 weeks | 10 participants |
| MBX-8025 (2 mg) | Participants Meet Rotterdam Criteria | Moderately advanced at 12 Weeks: Either abnormal Albumin or abnormal Total Bilirubin | 0 participants |
| MBX-8025 (2 mg) | Participants Meet Rotterdam Criteria | Moderately advanced: 52 Weeks, Either abnormal Albumin or abnormal Total Bilirubin | 0 participants |
| MBX-8025 (2 mg) | Participants Meet Rotterdam Criteria | Advanced: 12 Weeks, Both abnormal Albumin and abnormal Total Bilirubin | 0 participants |
| MBX-8025 (2 mg) | Participants Meet Rotterdam Criteria | Advanced: 52 Weeks Both abnormal Albumin and abnormal Total Bilirubin | 0 participants |
| MBX-8025 (5 mg) | Participants Meet Rotterdam Criteria | Advanced: 52 Weeks Both abnormal Albumin and abnormal Total Bilirubin | 3 participants |
| MBX-8025 (5 mg) | Participants Meet Rotterdam Criteria | Early Stage,12 Weeks | 38 participants |
| MBX-8025 (5 mg) | Participants Meet Rotterdam Criteria | Moderately advanced: 52 Weeks, Either abnormal Albumin or abnormal Total Bilirubin | 3 participants |
| MBX-8025 (5 mg) | Participants Meet Rotterdam Criteria | Advanced: 12 Weeks, Both abnormal Albumin and abnormal Total Bilirubin | 1 participants |
| MBX-8025 (5 mg) | Participants Meet Rotterdam Criteria | Early Stage, 52 weeks | 36 participants |
| MBX-8025 (5 mg) | Participants Meet Rotterdam Criteria | Moderately advanced at 12 Weeks: Either abnormal Albumin or abnormal Total Bilirubin | 7 participants |
| MBX-8025 (10 mg) | Participants Meet Rotterdam Criteria | Early Stage, 52 weeks | 42 participants |
| MBX-8025 (10 mg) | Participants Meet Rotterdam Criteria | Moderately advanced at 12 Weeks: Either abnormal Albumin or abnormal Total Bilirubin | 9 participants |
| MBX-8025 (10 mg) | Participants Meet Rotterdam Criteria | Advanced: 52 Weeks Both abnormal Albumin and abnormal Total Bilirubin | 1 participants |
| MBX-8025 (10 mg) | Participants Meet Rotterdam Criteria | Moderately advanced: 52 Weeks, Either abnormal Albumin or abnormal Total Bilirubin | 5 participants |
| MBX-8025 (10 mg) | Participants Meet Rotterdam Criteria | Early Stage,12 Weeks | 40 participants |
| MBX-8025 (10 mg) | Participants Meet Rotterdam Criteria | Advanced: 12 Weeks, Both abnormal Albumin and abnormal Total Bilirubin | 0 participants |
Secondary
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)
Time frame: 12 Weeks and 52 Weeks
Population: mITT Population The mITT population is defined as any enrolled subject who receives at least one dose of medication and has at least one post-baseline AP evaluation and who have confirmed PBC.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MBX-8025 (2 mg) | Percentage of Participants Meet Composite Endpoint Criteria of ALP and Total Bilirubin | Week 12 | 45.5 percentage of participants |
| MBX-8025 (2 mg) | Percentage of Participants Meet Composite Endpoint Criteria of ALP and Total Bilirubin | Week 52 | 63.6 percentage of participants |
| MBX-8025 (5 mg) | Percentage of Participants Meet Composite Endpoint Criteria of ALP and Total Bilirubin | Week 12 | 48.9 percentage of participants |
| MBX-8025 (5 mg) | Percentage of Participants Meet Composite Endpoint Criteria of ALP and Total Bilirubin | Week 52 | 53.3 percentage of participants |
| MBX-8025 (10 mg) | Percentage of Participants Meet Composite Endpoint Criteria of ALP and Total Bilirubin | Week 12 | 66.7 percentage of participants |
| MBX-8025 (10 mg) | Percentage of Participants Meet Composite Endpoint Criteria of ALP and Total Bilirubin | Week 52 | 67.3 percentage of participants |
Secondary
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.
Time frame: 12 weeks and 52 weeks
Population: mITT Population. The mITT population is defined as any enrolled subject who receives at least one dose of medication and has at least one post-baseline AP evaluation and who have confirmed PBC.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MBX-8025 (2 mg) | Percentage of Participants Meet Composite Endpoint of AP and Total Bilirubin Criteria at Week 12 and Week 52 | Week 12 | 45.5 percentage of subjects |
| MBX-8025 (2 mg) | Percentage of Participants Meet Composite Endpoint of AP and Total Bilirubin Criteria at Week 12 and Week 52 | Week 52 | 63.6 percentage of subjects |
| MBX-8025 (5 mg) | Percentage of Participants Meet Composite Endpoint of AP and Total Bilirubin Criteria at Week 12 and Week 52 | Week 12 | 48.9 percentage of subjects |
| MBX-8025 (5 mg) | Percentage of Participants Meet Composite Endpoint of AP and Total Bilirubin Criteria at Week 12 and Week 52 | Week 52 | 53.3 percentage of subjects |
| MBX-8025 (10 mg) | Percentage of Participants Meet Composite Endpoint of AP and Total Bilirubin Criteria at Week 12 and Week 52 | Week 12 | 66.7 percentage of subjects |
| MBX-8025 (10 mg) | Percentage of Participants Meet Composite Endpoint of AP and Total Bilirubin Criteria at Week 12 and Week 52 | Week 52 | 67.3 percentage of subjects |
Secondary
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.
Time frame: 12 weeks and 52 weeks
Population: mITT Population. The mITT population is defined as any enrolled subject who receives at least one dose of medication and has at least one post-baseline AP evaluation and who have confirmed PBC.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MBX-8025 (2 mg) | Percentage of Participants Meet Published PBC Response Criteria - Barcelona | Week 52 | 45.5 percentage of participants |
| MBX-8025 (2 mg) | Percentage of Participants Meet Published PBC Response Criteria - Barcelona | Week 12 | 9.1 percentage of participants |
| MBX-8025 (5 mg) | Percentage of Participants Meet Published PBC Response Criteria - Barcelona | Week 12 | 42.6 percentage of participants |
| MBX-8025 (5 mg) | Percentage of Participants Meet Published PBC Response Criteria - Barcelona | Week 52 | 66.7 percentage of participants |
| MBX-8025 (10 mg) | Percentage of Participants Meet Published PBC Response Criteria - Barcelona | Week 12 | 62.7 percentage of participants |
| MBX-8025 (10 mg) | Percentage of Participants Meet Published PBC Response Criteria - Barcelona | Week 52 | 65.3 percentage of participants |
Secondary
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.
Time frame: 12 weeks and 52 weeks
Population: mITT Population The mITT population is defined as any enrolled subject who receives at least one dose of medication and has at least one post-baseline AP evaluation and who have confirmed PBC.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MBX-8025 (2 mg) | Percentage of Participants Meet Published PBC Response Criteria - Paris I | Week 12 | 81.8 percentage of participants |
| MBX-8025 (2 mg) | Percentage of Participants Meet Published PBC Response Criteria - Paris I | Week 52 | 90 percentage of participants |
| MBX-8025 (5 mg) | Percentage of Participants Meet Published PBC Response Criteria - Paris I | Week 12 | 76.1 percentage of participants |
| MBX-8025 (5 mg) | Percentage of Participants Meet Published PBC Response Criteria - Paris I | Week 52 | 81.0 percentage of participants |
| MBX-8025 (10 mg) | Percentage of Participants Meet Published PBC Response Criteria - Paris I | Week 12 | 75.5 percentage of participants |
| MBX-8025 (10 mg) | Percentage of Participants Meet Published PBC Response Criteria - Paris I | Week 52 | 79.2 percentage of participants |
Secondary
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.
Time frame: 12 weeks and 52 weeks
Population: mITT Population. The mITT population is defined as any enrolled subject who receives at least one dose of medication and has at least one post-baseline AP evaluation and who have confirmed PBC.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MBX-8025 (2 mg) | Percentage of Participants Meet Published PBC Response Criteria - Paris II | Week 12 | 36.4 percentage of participants |
| MBX-8025 (2 mg) | Percentage of Participants Meet Published PBC Response Criteria - Paris II | Week 52 | 50.0 percentage of participants |
| MBX-8025 (5 mg) | Percentage of Participants Meet Published PBC Response Criteria - Paris II | Week 12 | 37.0 percentage of participants |
| MBX-8025 (5 mg) | Percentage of Participants Meet Published PBC Response Criteria - Paris II | Week 52 | 54.8 percentage of participants |
| MBX-8025 (10 mg) | Percentage of Participants Meet Published PBC Response Criteria - Paris II | Week 12 | 59.2 percentage of participants |
| MBX-8025 (10 mg) | Percentage of Participants Meet Published PBC Response Criteria - Paris II | Week 52 | 60.4 percentage of participants |
Secondary
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.
Time frame: 12 weeks and 52 weeks
Population: mITT Population. The mITT population is defined as any enrolled subject who receives at least one dose of medication and has at least one post-baseline AP evaluation and who have confirmed PBC.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MBX-8025 (2 mg) | Percentage of Participants Meet Published PBC Response Criteria - Toronto I | Week 52 | 63.6 percentage of subjects |
| MBX-8025 (2 mg) | Percentage of Participants Meet Published PBC Response Criteria - Toronto I | Week 12 | 63.6 percentage of subjects |
| MBX-8025 (5 mg) | Percentage of Participants Meet Published PBC Response Criteria - Toronto I | Week 12 | 51.1 percentage of subjects |
| MBX-8025 (5 mg) | Percentage of Participants Meet Published PBC Response Criteria - Toronto I | Week 52 | 57.8 percentage of subjects |
| MBX-8025 (10 mg) | Percentage of Participants Meet Published PBC Response Criteria - Toronto I | Week 12 | 78.4 percentage of subjects |
| MBX-8025 (10 mg) | Percentage of Participants Meet Published PBC Response Criteria - Toronto I | Week 52 | 71.4 percentage of subjects |
Secondary
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.
Time frame: 12 weeks and 52 weeks
Population: mITT Population. The mITT population is defined as any enrolled subject who receives at least one dose of medication and has at least one post-baseline AP evaluation and who have confirmed PBC.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MBX-8025 (2 mg) | Percent Change in Serum Alkaline Phosphatase (ALP) | Relative Change at Week 52 | -32.72 percentage Change | Standard Deviation 22.48 |
| MBX-8025 (2 mg) | Percent Change in Serum Alkaline Phosphatase (ALP) | Relative Change at Week 12 | -22.56 percentage Change | Standard Deviation 13.92 |
| MBX-8025 (5 mg) | Percent Change in Serum Alkaline Phosphatase (ALP) | Relative Change at Week 52 | -40.09 percentage Change | Standard Deviation 24.23 |
| MBX-8025 (5 mg) | Percent Change in Serum Alkaline Phosphatase (ALP) | Relative Change at Week 12 | -34.49 percentage Change | Standard Deviation 20.62 |
| MBX-8025 (10 mg) | Percent Change in Serum Alkaline Phosphatase (ALP) | Relative Change at Week 12 | -43.20 percentage Change | Standard Deviation 12.39 |
| MBX-8025 (10 mg) | Percent Change in Serum Alkaline Phosphatase (ALP) | Relative Change at Week 52 | -44.19 percentage Change | Standard Deviation 15.52 |
Secondary
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.
Time frame: 12 weeks and 52 weeks
Population: mITT Population. The mITT population is defined as any enrolled subject who receives at least one dose of medication and has at least one post-baseline AP evaluation and who have confirmed PBC.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MBX-8025 (2 mg) | UK-PBC Risk Score Value | 15 years, week 12 | 8.3008 units on a scale | Standard Deviation 3.9932 |
| MBX-8025 (2 mg) | UK-PBC Risk Score Value | 15 years, week 52 | 7.8325 units on a scale | Standard Deviation 4.3413 |
| MBX-8025 (2 mg) | UK-PBC Risk Score Value | 5 years, week 52 | 1.3145 units on a scale | Standard Deviation 0.7704 |
| MBX-8025 (2 mg) | UK-PBC Risk Score Value | 10 years week 12 | 4.5705 units on a scale | Standard Deviation 2.2479 |
| MBX-8025 (2 mg) | UK-PBC Risk Score Value | 5 years, week 12 | 1.3929 units on a scale | Standard Deviation 0.6976 |
| MBX-8025 (2 mg) | UK-PBC Risk Score Value | 10 years, week 52 | 4.3128 units on a scale | Standard Deviation 2.4649 |
| MBX-8025 (5 mg) | UK-PBC Risk Score Value | 10 years, week 52 | 7.2322 units on a scale | Standard Deviation 9.5794 |
| MBX-8025 (5 mg) | UK-PBC Risk Score Value | 5 years, week 12 | 2.2553 units on a scale | Standard Deviation 2.5145 |
| MBX-8025 (5 mg) | UK-PBC Risk Score Value | 5 years, week 52 | 2.3485 units on a scale | Standard Deviation 3.432 |
| MBX-8025 (5 mg) | UK-PBC Risk Score Value | 15 years, week 12 | 12.4002 units on a scale | Standard Deviation 12.1785 |
| MBX-8025 (5 mg) | UK-PBC Risk Score Value | 15 years, week 52 | 12.3028 units on a scale | Standard Deviation 14.5701 |
| MBX-8025 (5 mg) | UK-PBC Risk Score Value | 10 years week 12 | 7.1229 units on a scale | Standard Deviation 7.4904 |
| MBX-8025 (10 mg) | UK-PBC Risk Score Value | 15 years, week 52 | 9.9008 units on a scale | Standard Deviation 8.5396 |
| MBX-8025 (10 mg) | UK-PBC Risk Score Value | 10 years week 12 | 5.8293 units on a scale | Standard Deviation 5.3605 |
| MBX-8025 (10 mg) | UK-PBC Risk Score Value | 15 years, week 12 | 10.3469 units on a scale | Standard Deviation 9.1269 |
| MBX-8025 (10 mg) | UK-PBC Risk Score Value | 5 years, week 12 | 1.8124 units on a scale | Standard Deviation 1.7267 |
| MBX-8025 (10 mg) | UK-PBC Risk Score Value | 5 years, week 52 | 1.7244 units on a scale | Standard Deviation 1.6121 |
| MBX-8025 (10 mg) | UK-PBC Risk Score Value | 10 years, week 52 | 5.5607 units on a scale | Standard Deviation 5.0092 |