A Phase 2 interventional study of MBX-8025 2 mg Capsule and MBX-8025 5 mg Capsule in Primary Biliary Cirrhosis, sponsored by Gilead Sciences. Completed at 38 sites in 4 countries. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2022-07-14.
Sponsored by Gilead Sciences · Phase 2, Interventional, and Treatment
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)
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
228 studies on the registry are indexed under Cholangitis; 32 are open to participants now.
This study's enrollment of 119 is above the median of 56 across 150 interventional studies indexed under Cholangitis.
Browse Cholangitis studies →Gilead Sciences is the lead sponsor of 680 studies on the registry; 24 are open to participants now.
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Male or female with a diagnosis of PBC, by at least two of the following criteria:
Exclusion Criteria:
MBX-8025 2 mg capsule once daily
Drug: MBX-8025 2 mg Capsule
MBX-8025 5 mg capsule once daily
Drug: MBX-8025 5 mg Capsule
MBX-8025 10 mg capsule once daily
Drug: MBX-8025 10 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.
Also known as: 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.
Also known as: 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.
Also known as: MBX-8025, seladelpar
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
| Milestone | MBX-8025 (2 mg) | MBX-8025 (5 mg) | MBX-8025 (10 mg) |
|---|---|---|---|
| Started | 11 | 53 | 55 |
| Completed | 10 | 46 | 49 |
| Not completed | 1 | 7 | 6 |
| Withdrew: Adverse event | 0 | 3 | 0 |
| Withdrew: Withdrawal of informed consent | 1 | 3 | 2 |
| Withdrew: Lost to follow-up | 0 | 0 | 1 |
| Withdrew: Other | 0 | 1 | 3 |
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
| percentage change from baseline | MBX-8025 (2 mg) | MBX-8025 (5 mg) | MBX-8025 (10 mg) |
|---|---|---|---|
| Relative Change From Baseline in Serum Alkaline Phosphatase (ALP) at Week 8 | -26.06 ± 9.15 | -33.38 ± 17.81 | -41.42 ± 13.05 |
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.
| U/L | MBX-8025 (2 mg) | MBX-8025 (5 mg) | MBX-8025 (10 mg) |
|---|---|---|---|
| Absolute Change at Week 12 | -68.318 ± 63.276 | -135.902 ± 150.954 | -127.867 ± 60.284 |
| Absolute Change at Week 52 | -101.150 ± 107.956 | -158.310 ± 143.668 | -133.760 ± 76.151 |
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.
| U/L | MBX-8025 (2 mg) | MBX-8025 (5 mg) | MBX-8025 (10 mg) |
|---|---|---|---|
| Week 12 | -2.50 ± 16.72 | -1.13 ± 24.28 | -3.35 ± 10.55 |
| Week 52 | -7.05 ± 10.50 | -6.18 ± 13.98 | -6.14 ± 9.18 |
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.
| U/L | MBX-8025 (2 mg) | MBX-8025 (5 mg) | MBX-8025 (10 mg) |
|---|---|---|---|
| Week 12 | -5.59 ± 16.07 | -10.48 ± 21.41 | -10.87 ± 20.25 |
| Week 52 | -14.30 ± 25.12 | -17.29 ± 17.46 | -15.32 ± 13.89 |
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.
| U/L | MBX-8025 (2 mg) | MBX-8025 (5 mg) | MBX-8025 (10 mg) |
|---|---|---|---|
| Week 12 | -43.68 ± 56.87 | -75.35 ± 87.57 | -80.82 ± 109.06 |
| Week 52 | -78.60 ± 81.59 | -91.37 ± 102.23 | -88.08 ± 122.14 |
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.
| mg/dL | MBX-8025 (2 mg) | MBX-8025 (5 mg) | MBX-8025 (10 mg) |
|---|---|---|---|
| Week 12 | -0.010 ± 0.121 | -0.055 ± 0.161 | -0.067 ± 0.199 |
| Week 52 | 0.002 ± 0.152 | -0.028 ± 0.263 | -0.068 ± 0.190 |
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 | MBX-8025 (2 mg) | MBX-8025 (5 mg) | MBX-8025 (10 mg) |
|---|---|---|---|
| Week 12 | 45.5 | 48.9 | 66.7 |
| Week 52 | 63.6 | 53.3 | 67.3 |
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 | MBX-8025 (2 mg) | MBX-8025 (5 mg) | MBX-8025 (10 mg) |
|---|---|---|---|
| Week 12 | 81.8 | 76.1 | 75.5 |
| Week 52 | 90 | 81.0 | 79.2 |
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 | MBX-8025 (2 mg) | MBX-8025 (5 mg) | MBX-8025 (10 mg) |
|---|---|---|---|
| Week 12 | 36.4 | 37.0 | 59.2 |
| Week 52 | 50.0 | 54.8 | 60.4 |
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.
| percentage of subjects | MBX-8025 (2 mg) | MBX-8025 (5 mg) | MBX-8025 (10 mg) |
|---|---|---|---|
| Week 12 | 63.6 | 51.1 | 78.4 |
| Week 52 | 63.6 | 57.8 | 71.4 |
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.
| units on a scale | MBX-8025 (2 mg) | MBX-8025 (5 mg) | MBX-8025 (10 mg) |
|---|---|---|---|
| 5 years, week 12 | 1.3929 ± 0.6976 | 2.2553 ± 2.5145 | 1.8124 ± 1.7267 |
| 5 years, week 52 | 1.3145 ± 0.7704 | 2.3485 ± 3.432 | 1.7244 ± 1.6121 |
| 10 years week 12 | 4.5705 ± 2.2479 | 7.1229 ± 7.4904 | 5.8293 ± 5.3605 |
| 10 years, week 52 | 4.3128 ± 2.4649 | 7.2322 ± 9.5794 | 5.5607 ± 5.0092 |
| 15 years, week 12 | 8.3008 ± 3.9932 | 12.4002 ± 12.1785 | 10.3469 ± 9.1269 |
| 15 years, week 52 | 7.8325 ± 4.3413 | 12.3028 ± 14.5701 | 9.9008 ± 8.5396 |
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.
| score on a scale | MBX-8025 (2 mg) | MBX-8025 (5 mg) | MBX-8025 (10 mg) |
|---|---|---|---|
| Week 12 | -3.7 ± 6.4 | -5.5 ± 25.0 | -12.3 ± 22.3 |
| Week 52 | -3.3 ± 11.7 | -9.6 ± 22.5 | -16.5 ± 23.0 |
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).
| units on a scale | MBX-8025 (2 mg) | MBX-8025 (5 mg) | MBX-8025 (10 mg) |
|---|---|---|---|
| General Symptoms, Week 12 | 1.9 ± 2.7 | -0.7 ± 5.1 | -0.5 ± 3.6 |
| General Symptoms, Week 52 | 0.3 ± 2.4 | -1.4 ± 4.4 | -0.1 ± 4.4 |
| Itch, Week 12 | -0.4 ± 2.0 | -0.5 ± 3.4 | -0.8 ± 3.1 |
| Itch, Week 52 | 0.4 ± 2.7 | -1.3 ± 3.2 | -1.4 ± 3.7 |
| Fatigue, Week 12 | -1.5 ± 6.1 | -2.1 ± 10.4 | -3.0 ± 5.2 |
| Fatigue, Week 52 | -1.2 ± 7.8 | -3.0 ± 8.5 | -3.4 ± 6.3 |
| Cognitive Function, Week 12 | -0.9 ± 2.4 | -0.6 ± 5.7 | -0.7 ± 2.8 |
| Cognitive Function, Week 52 | -0.7 ± 7.6 | -1.4 ± 5.3 | -0.6 ± 2.5 |
| Social, Week 12 | 0.8 ± 2.8 | -0.5 ± 7.9 | -1.0 ± 6.3 |
| Social, Week 52 | -3.3 ± 5.2 | -1.6 ± 7.2 | -1.6 ± 6.2 |
| Emotional, Week 12 | -0.9 ± 1.6 | -1.0 ± 2.6 | -0.8 ± 2.1 |
| Emotional, Week 52 | -2.1 ± 2.3 | -1.3 ± 2.7 | -0.9 ± 2.1 |
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.
| percentage of participants | MBX-8025 (2 mg) | MBX-8025 (5 mg) | MBX-8025 (10 mg) |
|---|---|---|---|
| Week 12 | 9.1 | 42.6 | 62.7 |
| Week 52 | 45.5 | 66.7 | 65.3 |
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 from Baseline | MBX-8025 (2 mg) | MBX-8025 (5 mg) | MBX-8025 (10 mg) |
|---|---|---|---|
| Week 12 | -0.3 ± 1.6 | 0.1 ± 1.2 | 0.1 ± 1.0 |
| Week 52 | -0.7 ± 1.6 | 0.3 ± 1.1 | 0.2 ± 1.2 |
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
| units on a scale | MBX-8025 (2 mg) | MBX-8025 (5 mg) | MBX-8025 (10 mg) |
|---|---|---|---|
| Week 12 | -0.079 ± 0.260 | -0.292 ± 0.304 | -0.346 ± 0.269 |
| Week 52 | -0.180 ± 0.217 | -0.271 ± 0.354 | -0.404 ± 0.298 |
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.
| participants | MBX-8025 (2 mg) | MBX-8025 (5 mg) | MBX-8025 (10 mg) |
|---|---|---|---|
| Early Stage,12 Weeks | 11 | 38 | 40 |
| Early Stage, 52 weeks | 10 | 36 | 42 |
| Moderately advanced at 12 Weeks: Either abnormal Albumin or abnormal Total Bilirubin | 0 | 7 | 9 |
| Moderately advanced: 52 Weeks, Either abnormal Albumin or abnormal Total Bilirubin | 0 | 3 | 5 |
| Advanced: 12 Weeks, Both abnormal Albumin and abnormal Total Bilirubin | 0 | 1 | 0 |
| Advanced: 52 Weeks Both abnormal Albumin and abnormal Total Bilirubin | 0 | 3 | 1 |
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.
| percentage of subjects | MBX-8025 (2 mg) | MBX-8025 (5 mg) | MBX-8025 (10 mg) |
|---|---|---|---|
| Week 12 | 45.5 | 48.9 | 66.7 |
| Week 52 | 63.6 | 53.3 | 67.3 |
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.
| percentage Change | MBX-8025 (2 mg) | MBX-8025 (5 mg) | MBX-8025 (10 mg) |
|---|---|---|---|
| Relative Change at Week 12 | -22.56 ± 13.92 | -34.49 ± 20.62 | -43.20 ± 12.39 |
| Relative Change at Week 52 | -32.72 ± 22.48 | -40.09 ± 24.23 | -44.19 ± 15.52 |
Collected over Up to Week 56. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| MBX-8025 2 mg | 0/11 (0%) | 1/11 (9.1%) | 11/11 (100%) |
| MBX-8025 5 mg | 0/53 (0%) | 8/53 (15.1%) | 45/53 (84.9%) |
| MBX-8025 10 mg | 0/55 (0%) | 5/55 (9.1%) | 47/55 (85.5%) |
| Event | MBX-8025 2 mg | MBX-8025 5 mg | MBX-8025 10 mg |
|---|---|---|---|
| Rib fractureInjury, poisoning and procedural complications | 1/11 | 0/53 | 0/55 |
| Febrile neutropeniaBlood and lymphatic system disorders | 0/11 | 1/53 | 0/55 |
| Atrial fibrillationCardiac disorders | 0/11 | 1/53 | 0/55 |
| Abdominal pain upperGastrointestinal disorders | 0/11 | 1/53 | 0/55 |
| PneumoniaInfections and infestations | 0/11 | 1/53 | 1/55 |
| Femoral neck fractureInjury, poisoning and procedural complications | 0/11 | 1/53 | 0/55 |
| Post procedural haemorrhageInjury, poisoning and procedural complications | 0/11 | 1/53 | 0/55 |
| Procedural painInjury, poisoning and procedural complications | 0/11 | 1/53 | 0/55 |
| Intervertebral disc protrusionMusculoskeletal and connective tissue disorders | 0/11 | 1/53 | 0/55 |
| SyncopeNervous system disorders | 0/11 | 1/53 | 1/55 |
| Event | MBX-8025 2 mg | MBX-8025 5 mg | MBX-8025 10 mg |
|---|---|---|---|
| PruritusSkin and subcutaneous tissue disorders | 6/11 | 11/53 | 12/55 |
| DiarrhoeaGastrointestinal disorders | 4/11 | 7/53 | 9/55 |
| NauseaGastrointestinal disorders | 4/11 | 9/53 | 6/55 |
| NasopharyngitisInfections and infestations | 4/11 | 5/53 | 6/55 |
| Abdominal painGastrointestinal disorders | 3/11 | 3/53 | 3/55 |
| Abdominal pain upperGastrointestinal disorders | 3/11 | 7/53 | 5/55 |
| DyspepsiaGastrointestinal disorders | 3/11 | 2/53 | 1/55 |
| VomitingGastrointestinal disorders | 3/11 | 4/53 | 5/55 |
| FatigueGeneral disorders | 3/11 | 9/53 | 6/55 |
| Back painMusculoskeletal and connective tissue disorders | 3/11 | 5/53 | 3/55 |
18 to 75 years of age (inclusive)
| Age, Categorical(Participants) | MBX-8025 (2 mg) | MBX-8025 (5 mg) | MBX-8025 (10 mg) | Total |
|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 8 | 41 | 41 | 90 |
| >=65 years | 3 | 12 | 14 | 29 |
| Age, Continuous(years) | MBX-8025 (2 mg) | MBX-8025 (5 mg) | MBX-8025 (10 mg) | Total |
|---|---|---|---|---|
| Mean | 55.2 ± 9.6 | 57.5 ± 8.1 | 57.4 ± 9.7 | 56.4 ± 9.6 |
| Sex: Female, Male(Participants) | MBX-8025 (2 mg) | MBX-8025 (5 mg) | MBX-8025 (10 mg) | Total |
|---|---|---|---|---|
| Female | 11 | 51 | 50 | 112 |
| Male | 0 | 2 | 5 | 7 |
| Race/Ethnicity, Customized(Subjects) | MBX-8025 (2 mg) | MBX-8025 (5 mg) | MBX-8025 (10 mg) | Total |
|---|---|---|---|---|
| White | 10 | 50 | 49 | 109 |
| Black or African-American | 0 | 1 | 3 | 4 |
| Asian | 0 | 2 | 1 | 3 |
| American Indian or Alaska native | 0 | 0 | 1 | 1 |
| Other | 1 | 0 | 0 | 1 |
| Multiple | 0 | 0 | 1 | 1 |
| Region of Enrollment(participants) | MBX-8025 (2 mg) | MBX-8025 (5 mg) | MBX-8025 (10 mg) | Total |
|---|---|---|---|---|
| Canada | 0 | 5 | 1 | 6 |
| United States | 0 | 39 | 43 | 82 |
| United Kingdom | 11 | 5 | 4 | 20 |
| Germany | 0 | 4 | 7 | 11 |
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