E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary Biliary Cirrhosis |
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E.1.1.1 | Medical condition in easily understood language |
Primary biliary cirrhosis (PBC) is a liver disease in which the bile ducts in the liver become damaged, leading to a build-up of bile in the liver which can damage it and eventually lead to scarring. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036680 |
E.1.2 | Term | Primary biliary cirrhosis |
E.1.2 | System Organ Class | 100000004871 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to evaluate the effect of MBX-8025 on AP levels. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are: 1. To evaluate the safety and tolerability of MBX-8025 in subjects with PBC 2. To evaluate the effects of MBX-8025 on PBC response criteria 3. To evaluate the effects of MBX-8025 on other markers of liver function, lipids, pruritus and Quality of Life (QoL)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 (Anti-Mitochondrial Antibodies) titers (>1/40 on immunofluorescence or M2 positive by 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 six months 5. AP ≥ 1.67 ULN 6. For females of reproductive potential, use of at least one barrier contraceptive and a second effective birth control method, during the study, and for at least two weeks after the last dose For male subjects, use of appropriate contraception (e.g., condoms) so their female partners of reproductive potential do not become pregnant during the study, and for at least two weeks after the last dose
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E.4 | Principal 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 ≥ 2 times ULN 3. Total bilirubin >2 times ULN 4. Auto-immune hepatitis 5. Primary sclerosing cholangitis 6. Known histroy of alpha-1-Antitrypsin deficiency 7. Known history of chronic viral hepatitis 8. Creatine kinase above ULN 9. For females, pregnancy or breast-feeding 10. Use of colchicine, methotrexate, azathioprine or systemic steroids in the two months preceding screening 11. Use of an experimental treatment for PBC 12. Use of an experimental or unapproved immunosuppressant 13. 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
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E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate the effect of MBX-8025 on Alkaline Phosphatase (AP) Levels |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
End of Treatment - Week 12 |
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E.5.2 | Secondary end point(s) |
1. Composite endpoint of AP and Total Bilirubin: • AP < 1.67 ULN and Total Bilirubin within normal limit and • > 15% decrease in AP 2. Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Gamma-Glutamyl Transpeptidase (GGT), 5’nucleotidase, Bilirubin (Total, Conjugated, Unconjugated), and bone-specific AP Triglycerides (TG), Total Cholesterol (TC), High Density Lipoprotein Cholesterol (HDL-C), and Low Density Lipoprotein Cholesterol (LDL-C). 3. Published PBC response criteria (Paris I and II, Toronto I and II), UK-PBC risk score 4. 5D-itch scale, pruritus VAS 5. PBC-40 QoL
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Visit 2 (Week 0), Visit 3 (Week 2), Visit 4 (Week 4), Visit 5 (Week 8), Visit 6 (Week 12). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Germany |
Poland |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |