| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Primary Biliary Cholangitis |
|
| 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. |
|
| 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 | 100000004871 |
|
| 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 |
|
| E.2.2 | Secondary objectives of the trial |
- To evaluate the long-term efficacy of seladelpar
- To evaluate the effect of seladelpar on patient reported outcome (pruritus)
- To evaluate population pharmacokinetics and exposure-response
relationship of seladelpar |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subjects who successfully completed a previous study with seladelpar will be invited to continue their treatment in the long-term study.
1. Must have given written informed consent (signed and dated)
2. Participated in a PBC study with seladelpar and successfully completed the study
3. In the investigator’s opinion, subject derived a net benefit, from participation in a PBC study with seladelpar
4. 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 |
|
| E.4 | Principal exclusion criteria |
Exclusion criteria are applicable only for:
- subjects with study drug interruption greater than four weeks prior to Day 1 of this study.
- Subjects participated in CB8025-21838 irrespective of study drug interruption
1. Treatment-related adverse event 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 x ULN
5. MELD ≥ 15
6. Evidence of advanced PBC as defined by the Rotterdam criteria
(albumin below 1× LLN AND total bilirubin above 1 × ULN)
7. Creatine kinase above 2.5 × ULN
8. eGFR below 60 mL/min/1.73 m2 (calculated by MDRD formula)
9. Auto-immune hepatitis
10. Primary sclerosing cholangitis
11. Known history of alpha-1-antitrypsin deficiency
12. Known history of chronic viral hepatitis
13. For females, pregnancy or breast-feeding
14. Use of colchicine, methotrexate, azathioprine or long-term use of systemic steroids (>2 weeks) within two months prior to screening
15. Current use of fibrates
16. Current use of obeticholic acid
17. Use of an experimental or unapproved treatment for PBC 16. Use of experimental or unapproved immunosuppressant
18. Treatment with any other investigational therapy or medical device
within 30 days or within five 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 |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Treatment Emergent Adverse Events (TEAEs) (NCI CTCAE Version 5.0),
biochemistry and hematology results |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
1. Occurrence of the following adjudicated Clinical Events:
* Death (any cause)
* Liver transplantation
* MELD score ≥ 15
* Uncontrolled ascites (diuretic resistant)
* Hepatocellular carcinoma
* 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 AP and Total Bilirubin
* Proportion of subjects with normalization of AP
- Relative and absolute changes of: Alkaline phosphatase (AP)
- Aspartate aminotransferase (AST)
- Alanine aminotransferase (ALT)
- Gamma-glutamyl transferase (GGT)
- Bilirubin (Total, Direct, Indirect)
- Triglycerides (TG)
- Total Cholesterol (TC)
- High Density Lipoprotein Cholesterol (HDL-C)
- Low Density Lipoprotein Cholesterol (LDL-C)
3. Change in pruritus numerical rating scale (NRS)
4. Pharmacokinetics of seladelpar and its metabolites (M1, M2, M3) and exposure-response relationship of seladelpar |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | 9 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 64 |
| 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 |
| Australia |
| Belgium |
| Canada |
| Chile |
| France |
| Germany |
| Greece |
| Hungary |
| Israel |
| Italy |
| Korea, Republic of |
| Mexico |
| Netherlands |
| New Zealand |
| Poland |
| Romania |
| Russian Federation |
| Serbia |
| Spain |
| United Kingdom |
| United States |
|
| 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
|
|
| 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 |
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