Double-blind, randomized, placebo-controlled Phase III study comparing Norursodeoxycholic acid capsules versus placebo in the treatment of primary sclerosing cholangitis

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

Identifiant de l'essai ICTRP
EUCTR2016-003367-19 (ICTRP)

Titre officiel (approuvé par le comité d'éthique)
Double-blind, randomized, placebo-controlled, phase III study comparing norursodeoxycholic acid capsules with placebo in the treatment of primary sclerosing cholangitis (BASEC)

Titre académique
Double-blind, randomized, placebo-controlled, phase III study comparing norursodeoxycholic acid capsules with placebo in the treatment of primary sclerosing cholangitis (ICTRP)

Titre public
A study to compare norursodeoxycholic acid with placebo in the treatment of primary sclerosing cholangitis (ICTRP)

Maladie en cours d'investigation
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: 20.1Level: LLTClassification code 10036732Term: Primary sclerosing cholangitisSystem Organ Class: 10019805 - Hepatobiliary disorders;Therapeutic area: Diseases [C] - Digestive System Diseases [C06] (ICTRP)

Intervention étudiée

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

(ICTRP)

Type d'essai
Interventional clinical trial of medicinal product (ICTRP)

Plan de l'étude
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 (ICTRP)

Critères d'inclusion/exclusion
Gender:
Female: yes
Male: yes

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 a 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 study drug. 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.

Inclusion Criteria for the open-label extension {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
(ICTRP)

Exclusion criteria:
1. History or presence of other concomitant liver diseases including.
4. Secondary causes of Sclerosing Cholangitis
11. Total bilirubin > 4.0 mg/dL (> 68 ?mol/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 (elevated levels [4.2-10 ?U/mL] are acceptable if fT4 is measured and within the 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 the 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 able to express their consent (e.g. due to mental impairment).


Critères d'évaluation principaux et secondaires
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.;Secondary Objective: To study safety and tolerability (Adverse Events, laboratory parameters) of norUDCA,
To assess quality of life.
;Primary end point(s): Partial normalization of s-ALP and no worsening of disease stage as determined by the Ludwig stage.

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

Secondary end point(s): Partial normalization of s-ALP and no worsening of disease stage as determined by the modified Nakanuma score at the week 96 visit compared to baseline as key secondary endpont. Secondary endpoints with regard to liver stiffness, fibrosis stage, liver histology, dominant strictures, quality of life as other secondary endpoints.;Timepoint(s) of evaluation of this end point: week 96 (ICTRP)

Date d'enregistrement
12.02.2018 (ICTRP)

Inclusion du premier participant
25.04.2018 (ICTRP)

Sponsors secondaires
non disponible

Contacts supplémentaires
Department of Clinical Research, zentrale@drfalkpharma.de, 004976115140, Dr. Falk Pharma GmbH (ICTRP)

ID secondaires
NUC-5/PSC, 2016-003367-19-DE (ICTRP)

Résultats-Données individuelles des participants
non disponible

Informations complémentaires sur l'essai
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-003367-19 (ICTRP)