E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary Sclerosing Cholangitis (PSC) is a slowly progressing chronic cholestatic liver disease of assumed autoimmune, but finally unidentified etiology, characterized by a chronic inflammatory and fibro-obliterative destruction of extra-, and intrahepatic bile ducts. The disease is characterized by diffuse inflammation, fibrosis, and strictures of the intra- and/or extrahepatic bile ducts with an impaired biliary secretion of potentially aggressive bile fluid often leading to cirrhosis. |
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E.1.1.1 | Medical condition in easily understood language |
Primary Sclerosing Cholangitis (PSC) is a slowly progressing chronic liver disease characterized by changes in the gall ducts inside and/or outside the liver, such as narrowing or enlargement. |
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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 | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036732 |
E.1.2 | Term | Primary sclerosing cholangitis |
E.1.2 | System Organ Class | 100000004871 |
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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 show the superiority of norursodeoxycholic acid (norUDCA) compared to placebo in the treatment of Primary Sclerosing Cholangitis (PSC) with regard to prevention of disease progression. |
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E.2.2 | Secondary objectives of the trial |
To study safety and tolerability (Adverse Events, laboratory parameters) of norUDCA,
To assess quality of life.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent.
2. Males or females.
3. Verified PSC.
4. Liver biopsy available.
5. If pre-treated with ursodeoxycholic acid (UDCA), then stable UDCA dose for ≥ 3 months prior to baseline and must not have exceeded 20 mg/kg/d.
6. Alkaline Phosphatase > 1.5 x upper limit of normal (ULN) at baseline.
7. PSC patients with or without Inflammatory Bowel Disease (IBD; patients without a definite diagnostic exclusion of IBD need a colonoscopy with segmental biopsy prior to the baseline visit)
8. Women of child-bearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile, who are sexually active have to apply a highly effective method of birth control with a low failure rate (i.e., less than 1% per year) when used constantly and correctly such as combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner, or sexual abstinence, throughout the treatment period and for four weeks following the last dose of study treatment. Hormonal methods other than levonorgestrel containing devices or medroxyprogesterone injections should be supplemented with use of a male condom. Women of non-childbearing potential may be included if surgically sterile or post-menopausal for at least 2 years. The investigator is responsible for determining whether the patient has this adequate birth control for study participation. |
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E.4 | Principal exclusion criteria |
1. History or presence of other concomitant liver diseases
4. Secondary causes of Sclerosing Cholangitis.
11. Total bilirubin > 4.0 mg/dl (> 68 µmol/L) at screening or baseline.
13. Any known relevant infectious disease (e.g., active tuberculosis, AIDS defining diseases).14. Abnormal renal function.
15. Thyroid-stimulating hormone (TSH) > ULN at screening.
17. Any active malignant disease.
18. Known intolerance/hypersensitivity to study drug, or drugs of similar chemical structure or pharmacological profile.
19. Well-founded doubt about the patient’s cooperation.
20. Existing or intended pregnancy or breast-feeding.
21. Participation in another clinical trial within the last 30 days.
22. Patients who have an absolute contraindication for liver biopsy. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Partial normalization of s-ALP and no worsening of disease stage.
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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) |
Secondary endpoints with regard to liver stiffness, fibrosis stage, liver histology, s-ALP levels, dominant strictures, quality of life |
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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 | No |
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) | 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 | 2 |
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 | 70 |
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 |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | 6 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 3 |