Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruiting
Participants planned
560
Countries
1
Sites
12
Primary sclerosing cholangitis (PSC)
Does treatment with simvastatin prolong survival free from bile duct cancer, variceal bleeding and transplantation in PSC?
Key facts
- Sponsor
- Karolinska University Hospital, Karolinska University Hospital
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 4 May 2020 → ongoing
- Decision date (initial)
- 2024-02-26
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
External identifiers
- EU CT number
- 2024-511053-22-00
- EudraCT number
- 2018-000814-39
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy
Does treatment with simvastatin prolong survival free from bile duct cancer, variceal bleeding and transplantation in PSC?
Secondary objectives 3
- Does treatment with simvastatin affect known surrogate markers for treatment effects in PSC such as a serum concentration of alkaline phosphatase, serum concentration of bilirubin or elastography?
- Does treatment with simvastatin affect the progress of the disease, measured with MELD score, Child Pugh score, coloniographic progress on MR/MRCP, cirrhosis development, PSC-related symptoms (itching or bacterial colangitis requiring antibiotic treatment), ascites and encephalopathy?
- Does treatment with simvastatin prevent development of colon cancer or dysplasia?
Conditions and MedDRA coding
Primary sclerosing cholangitis (PSC)
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- Patients with a cholangiographically verified PSC and/or liverbiopsy with and without IBD (patients with a present autoimmun hepatit and small duct PSC can be included)
- Men and women ≥18 years but ≤75 years
- Patient has given written consent to participate in the study
- MR/MRCP within 4 months
- Coloscopy within 24 months if the patient has a known IBD
- Female of childbearing potential must agree to use a highly efficient method of contraception during the study participation.
Exclusion criteria 9
- Patients on waiting list for transplantation
- Transplanted patients
- Patients with severe liver failure ≥ Child B 9 points
- Previous varices bleeding secondary to end stage liver disease
- Previous cholangiocarcinoma
- Patients with secondary sclerosing cholangitis
- Patients who have been taking any statin medication during the last 3 months
- Intolerance to statins
- Pregnancy and breastfeeding
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 4
- Number of days from randomisation to death
- Number of days from randomisation to listing of liver transplantation
- Number of days from randomisation to first variceal bleeding
- Number of days from randomization to diagnosis bile duct cancer, gall bladder cancer or hepatocellular cancer (diagnosed with characteristic x-ray (focal) or histological/cytological diagnosis).
Secondary endpoints 9
- Serumconcentrations of alkaline phosphatase
- Serumconcentration of bilirubin
- MELD Score
- Child Pugh Score
- Progress of cholangiographic image with MR
- Elastography
- Symptoms related to PSC (itching or bacterial colangitis requiring treatment, ascites, encephalopathy)
- Dysplasia in the biliary tract or gall bladder
- Development of colon cancer or dysplasia
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Simvastatin Sandoz 40 mg filmdragerade tabletter
PRD770432 · Product
- Active substance
- Simvastatin
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 40 mg milligram(s)
- Max total dose
- 40 mg milligram(s)
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- C10AA01 — SIMVASTATIN
- Marketing authorisation
- 17536
- MA holder
- SANDOZ A/S
- MA country
- Sweden
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 1
Placebo for Simvastatin Sandoz 40 mg tablets.
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Karolinska University Hospital
- Sponsor organisation
- Karolinska University Hospital
- Address
- Eugeniavagen 3
- City
- Solna
- Postcode
- 171 64
- Country
- Sweden
Scientific contact point
- Organisation
- Karolinska University Hospital
- Contact name
- Annika Bergquist
Public contact point
- Organisation
- Karolinska University Hospital
- Contact name
- Annika Bergquist
Karolinska University Hospital
- Sponsor organisation
- Karolinska University Hospital
- Address
- Eugeniavagen 3
- City
- Solna
- Postcode
- 171 64
- Country
- Sweden
Scientific contact point
- Organisation
- Karolinska University Hospital
- Contact name
- Annika Bergquist
Public contact point
- Organisation
- Karolinska University Hospital
- Contact name
- Annika Bergquist
Sponsor responsibilities
- Article 77 compliance
- Karolinska University Hospital
- Contact point sponsor
- Karolinska University Hospital
- Article 77 implementation
- Karolinska University Hospital
Locations
1 EU/EEA country · 12 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Sweden | Ongoing, recruiting | 560 | 12 |
| Rest of world | — | 0 | — |
Investigational sites
Sahlgrenska University Hospital-Vastra Gotalandsregionen
Department of Gastroenterology, Diagnosvagen 11, Harlanda, Gothenburg
Region Skane Skanes Universitetssjukhus
Department of Gastroenterology, St. Johns, Fritz Bauers Gata 5, Malmo
Sahlgrenska University Hospital-Vastra Gotalandsregionen
Department of Gastroenterology, Bla Straket 5, 413 46, Goteborg
Karolinska University Hospital
Medical Unit Upper Abdominal, Halsovagen, Flemingsberg, Huddinge
Region Oestergoetland
Department of Gastroenterology, St Larsgatan 49 B, S St Lars, Linkoping
Region Vaesterbotten
Department of Gastroenterology, Koksvagen 11, Alidhem, Umea
Region Vaermland
Department of Gastroenterology, Rosenborgsgatan 50, 652 33, Karlstad
Danderyds Sjukhus AB
Department of Gastroenterology, Morbygardsvagen 88, 182 88, Danderyd
Skaraborg Hospital-Vastra Gotalandsregionen
Department of gastroenterology, Mellbygatan 11-15, 531 51, Lidkoping
Karolinska University Hospital
Medical unit Inflammation and Ageing, Eugeniavagen 3, 171 64, Solna
Region Oerebro Laen
Medical clinic, Sodra Grev Rosengatan, 701 85, Orebro
Uppsala University Hospital
Department of Gastroenterology, Akademiska Sjukhuset, 751 85, Uppsala
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Sweden | 2020-05-04 | 2020-10-29 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 6 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | Protocol 2024-511053-22-00 | 6.0 |
| Protocol (for publication) | Protocol 2024-511053-22-00 SM 1_TC | 6.0 |
| Recruitment arrangements (for publication) | Recruitment Arrangements | 2 |
| Subject information and informed consent form (for publication) | SIS and ICF SE | 2.4 |
| Subject information and informed consent form (for publication) | SIS and IFC SE 2024-511053-22-00 SM-1_TC | 2.4 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPC_Simvastatin | 1 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-02-13 | Sweden | Acceptable 2024-02-26
|
2024-02-26 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-04-30 | Sweden | Acceptable 2024-06-10
|
2024-07-08 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-11-17 | Sweden | Acceptable 2026-01-07
|
2026-01-09 |