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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Dr. Falk Pharma GmbH

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

6 Dec 2017 → 27 Mar 2026

Decision date (initial)

2024-10-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Dr. Falk Pharma GmbH

External identifiers

EU CT number

2023-510200-42-00

EudraCT number

2016-003367-19

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy

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 objectives 2

1. To study safety and tolerability (Adverse Events, laboratory parameters) of norUDCA
2. To assess quality of life

Conditions and MedDRA coding

primary sclerosing cholangitis (PSC)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Signed informed consent.
2. Males or females.
3. Verified PSC.
4. Liver biopsy available.
5. 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.
6. Inclusion Criteria for the open-label extension (OLE) phase: 1. Signed additional informed consent for OLE phase
7. Inclusion Criteria for the open-label extension (OLE) phase: 2. DBE phase completed with Visit 22

Exclusion criteria 14

1. History or presence of other concomitant liver diseases including.
2. Secondary causes of Sclerosing Cholangitis.
3. Total bilirubin > 4.0 mg/dL (> 68 μmol/L) at screening or baseline.
4. Any known relevant infectious disease (e.g., active tuberculosis, AIDS defining diseases).
5. Abnormal renal function.
6. Thyroid-stimulating hormone (TSH) > ULN at screening (elevated levels [4.2-10 μU/mL] are acceptable if fT4 is measured and within the normal range).
7. 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.
8. Any active malignant disease.
9. Known intolerance/hypersensitivity to study drug, or drugs of similar chemical structure or pharmacological profile.
10. Well-founded doubt about the patient's cooperation.
11. Existing or intended pregnancy or breast-feeding.
12. Participation in another clinical trial within the last 30 days prior to screening visit.
13. Patients who have an absolute contraindication for liver biopsy.
14. 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).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Partial normalization of s-ALP and no worsening of disease stage as determined by the Ludwig stage.

Secondary endpoints 1

1. 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. Liver stiffness, fibrosis stage, liver histology, dominant strictures, quality of life as other secondary endpoints.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Dr. Falk Pharma GmbH

Sponsor organisation

Dr. Falk Pharma GmbH

Address

Leinenweberstrasse 5, Hochdorf Hochdorf

City

Freiburg Im Breisgau

Postcode

79108

Country

Germany

Scientific contact point

Organisation

Dr. Falk Pharma GmbH

Contact name

CTIS – Scientific Request

Public contact point

Organisation

Dr. Falk Pharma GmbH

Contact name

Clinical Research and Development, Dr. Falk Pharma GmbH

Third parties 6

Locations

9 EU/EEA countries · 25 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 95 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications