A study to compare norursodeoxycholic acid with placebo in the treatment of primary sclerosing cholangitis

• Register: EUCTR
• Last refreshed on: 3 February 2025
• Main ID: EUCTR2016-003367-19-NL
• Date of registration: 06/02/2018
• Prospective Registration: Yes
• Primary sponsor: Dr. Falk Pharma GmbH
• Public title: A study to compare norursodeoxycholic acid with placebo in the treatment of primary sclerosing cholangitis
• Scientific title: Double-blind, randomized, placebo-controlled, phase III study comparing norursodeoxycholic acid capsules with placebo in the treatment of primary sclerosing cholangitis
• Date of first enrolment: 22/01/2019
• Target sample size: 300
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-003367-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Czech Republic, Czechia, Denmark, Finland, France, Germany, Hungary, Ireland, Italy, Lithuania, Netherlands, Norway, Poland, Russian Federation, Spain, Sweden, Switzerland, United Kingdom

Contacts

• Name: Department of Clinical Research
• Affiliation: Dr. Falk Pharma GmbH

• Name: Department of Clinical Research
• Affiliation: Dr. Falk Pharma GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
1. Signed informed consent.
2. Males or females.
3. Verified PSC.
4. Liver biopsy available.
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 (only accepted as highly effective contraceptive measure if it is the usual and preferred lifestyle of the patient), throughout the treatment period and for four weeks following the last dose of the study drug. Hormonal methods other than levonorgestrel containing devices or medroxyprogestrone injections should be supplemented with use of 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 determing whether the patient has this adequate birth control for study participation.

Inclusion criteria for the OLE phase:
1. Signed additional informed consent for OLE phase
2. DBE phase completed with Visit 22
Are the trial subjects under 18? yes
Number of subjects for this age range: 50
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 210
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

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 relevant infectious disease (e.g., active tuberculosis, AIDS defining diseases).
14. Abnormal renal function.
15. Thyroid-stimulating hormone (TSH) > ULN at screening (elevated levels are acceptable if fT4 is measured and within normal range).
16. Any severe concomitant cardiovascular, renal, endocrine, or psychiatric disorder, which in the opinion of the investigator might have an influence on the patient's compliance or on the interpretation of results, or patient with atrial fibrillation or any disorder which in the opinion of the investigator may affect the patient's safety.
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 prior to screening visit.
22. patients who have an absolute contraindication for liver biopsy.
23. imprisoned persons, persons admitted to nursing homes, persons under legal guardianship, and persons not bale to express their consent (e.g. due to mental impairment).


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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.
MedDRA version: 20.1 Level: LLT Classification code 10036732 Term: Primary sclerosing cholangitis System Organ Class: 10019805 - Hepatobiliary disorders

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Product Name: Norursodeoxycholic acid
Pharmaceutical Form: Capsule
INN or Proposed INN: Norucholic acid
CAS Number: 99697-24-2
Current Sponsor code: NorUDCA
Other descriptive name: Norursodeoxycholic acid, NCA
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: 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.

Primary end point(s): Partial normalization of s-ALP to < 1.5x ULN and no worsening of disease stage as determined by the Ludwig stage at the week 96 visit compared to baseline

Secondary Objective: To study safety and tolerability (Adverse Events, laboratory parameters) of norUDCA,
To assess quality of life.

Timepoint(s) of evaluation of this end point: Visit 2 and Visit 14

Secondary Outcome(s)

Secondary end point(s): Partial normalization of s-ALP to < 1.5x ULN and no worsening of disease stage as determined by the modified Nakanuma score at the week 96 visit compared to baseline (derivation according to derivation of the primary efficacy variable)

Timepoint(s) of evaluation of this end point: week 96

Secondary ID(s)

2016-003367-19-DE

NUC-5/PSC

Source(s) of Monetary Support

Dr. Falk Pharma GmbH

Ethics review

Status: Approved
Approval date: 22/01/2019
Contact: