E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary Biliary Cholangitis |
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E.1.1.1 | Medical condition in easily understood language |
A long-term liver disease in which the bile ducts in the liver become damaged. This gradually leads 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 | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036680 |
E.1.2 | Term | Primary biliary cirrhosis |
E.1.2 | System Organ Class | 10019805 - Hepatobiliary disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the long-term safety and tolerability of seladelpar |
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E.2.2 | Secondary objectives of the trial |
To evaluate the long-term efficacy of seladelpar, and the effect of seladelpar on patient-reported outcomes (pruritus) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Must have given informed consent (signed and dated) 2. Participated in a previous PBC study with seladelpar (including CB8025-21629, CB8025-31735, or CB8025-21838) or future PBC studies with seladelpar that allow rollover into CB8025-31731-RE, or were previously enrolled in study CB8025-31731 prior to the early termination of the study, and meet eligibility criteria for the current study. 3. 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 |
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E.4 | Principal exclusion criteria |
Exclusion criteria are only applicable for subjects with a study drug interruption greater than 4 weeks prior to Day 1 of this study and for subjects who participated in CB8025-21838 irrespective of seladelpar interruption 1. Treatment-related AE leading to study drug discontinuation in a previous PBC study with seladelpar 2. 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) 3. AST or ALT above 3 × ULN 4. Total bilirubin above 2 × ULN 5. Model for End-Stage Liver Disease (MELD) score ≥ 15 6. Evidence of advanced PBC as defined by the Rotterdam criteria (albumin below 1 × lower limit of normal AND total bilirubin above 1 × ULN) 7. Estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m2 (calculated by Modification of Diet in Renal Disease formula) 8. Auto-immune hepatitis 9. Primary sclerosing cholangitis 10. Known history of alpha-1-antitrypsin deficiency 11. Known history of chronic viral hepatitis 12. For females, pregnancy or breast-feeding 13. Use of colchicine, methotrexate, azathioprine or long-term use of systemic steroids (e.g. prednisone, prednisolone, budesonide) (>2 weeks) within 2 months prior to Screening 14. Current use of fibrates or use of fibrates within 3 months prior to Screening 15. Current use of obeticholic acid or use of obeticholic acid within 3 months prior to Screening 16. Use of an experimental or unapproved treatment for PBC within 3 months prior to Screening 17. History of malignancy diagnosed or treated, actively or within 2 years, or active evaluation for malignancy; localized treatment of squamous or non-invasive basal cell skin cancers and cervical carcinoma in-situ is allowed if appropriately treated prior to Screening 18. Treatment with any other investigational therapy or medical device within 30 days or within 5 half-lives, whatever is longer, prior to Screening 19. 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) |
Treatment-emergent AEs (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] Version 5.0), biochemistry and hematology results are collected |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Occurrence of the following adjudicated PBC clinical outcomes: -Overall death -Liver transplantation -MELD score ≥ 15 for at least 2 consecutive visits -Ascites requiring treatment -Hospitalization for new onset or recurrence, of any: -Variceal bleeding, Hepatic encephalopathy (as defined by a West Haven score ≥ 2), Spontaneous bacterial peritonitis (confirmed by culture from diagnostic paracentesis) 2. Biochemical markers: -Response on composite of ALP and total bilirubin -Proportion of subjects with normalization of ALP -Relative and absolute changes of the following: -Alkaline phosphatase (ALP) -Aspartate aminotransferase (AST) -Alanine aminotransferase (ALT) -Gamma-glutamyl transferase (GGT) -Bilirubin (total, direct, indirect) 3. Change from Baseline in pruritus NRS |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 72 |
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 |
Argentina |
Chile |
New Zealand |
Australia |
Canada |
Israel |
Korea, Republic of |
Mexico |
Russian Federation |
United Kingdom |
United States |
Belgium |
France |
Germany |
Greece |
Hungary |
Italy |
Netherlands |
Poland |
Romania |
Spain |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |