Overview
Sponsor-declared trial summary
Phase
Phase III and Phase IV (Integrated)
Status
Ended
Participants planned
8
Countries
1
Sites
1
Bile acid synthesis defects
To investigate the long-term safety of personalized cholic acid capsules treatment of patients with bile acid synthesis defects based on clinical and biochemical parameters.
Key facts
- Sponsor
- Amsterdam UMC Stichting
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years, 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Trial duration
- completed 17 Mar 2025
- Decision date (initial)
- 2024-11-25
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- No
External identifiers
- EU CT number
- 2024-518652-23-00
- EudraCT number
- 2019-001528-37
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Therapy, Safety
To investigate the long-term safety of personalized cholic acid capsules treatment of patients with bile acid synthesis defects based on clinical and biochemical parameters.
Secondary objectives 2
- Investigate the long-term effect of CA treatment on clinical and biochemical parameters.
- Determine the feasibility of personalized treatment based upon pharmacokinetics of CA and clinical and biochemical parameters.
Conditions and MedDRA coding
Bile acid synthesis defects
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 2
- Bile acid synthesis defect due to 3β-hydroxy-Δ5-C27-steroid oxidoreductase-, Δ4-3-oxosteroid-5β-reductase-, α-methylacyl-CoA racemase (AMACR)-, cholesterol 7a-hydroxylase (CYP7A1) deficiency OR Zellweger spectrum disorder
- At least one of the following hallmarks: steatorrhea (confirmed per local protocol), elevated transaminases (ALAT and/or ASAT), developmental delay, neurological symptoms
Exclusion criteria 8
- Short life expectancy of < 12 months (severe multiple organ dysfunction)
- Decompensated liver cirrhosis
- High bilirubin serum levels (conjugated bilirubin > 20 μmol/L)
- Prolonged prothrombin time (PT > 15s not due to vitamin K deficiency)
- Pregnancy and high total bile acid serum level ( > 40μmol/L)
- Allergy to one of the components of CA capsules.
- Increased liver enzymes during previous CA treatment (for ZSD)
- Normal biochemical parameters (THCA and/or DHCA ≤1.0 μmol/L) (for ZSD)
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 3
- Degree of suppression of endogenous bile acid synthesis (decrease in serum [and urine] DHCA and THCA bile acid intermediates)
- Type and number of adverse events
- Type and number of side effects
Secondary endpoints 9
- Increase in normal primary bile acids (increase in urine cholic acid [CA])
- Change in serum ALT, AST, transaminases, γ-glutamyltrans- peptidase, conjugated bilirubin, total bilirubin levels, gamma-GT, alkaline phosphatase, alpha-1-phetoprotein
- Change in liver protein synthesis (determined by albumin, pre-albumin and prothrombin time [PT])
- Change in degree of coagulopathy (measured by PT, aPTT, Factor V and Factor VII)
- Change in weight gain (weight-for-height percentile)
- Change total body length growth rate (cm/year; only in those with remaining growth potential)
- Change in fat soluble vitamins (A,D, E) level and total cholesterol
- Development of fibrosis/cirrhosis (determined by fibroscan or US elastography)
- Neurological development
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
SUB13348MIG · Substance
- Active substance
- Cholic Acid
- Pharmaceutical form
- CAPSULE, HARD
- Route of administration
- ORAL
- Max daily dose
- 20 mg/kg milligram(s)/kilogram
- Max total dose
- 20 mg/kg milligram(s)/kilogram
- Max treatment duration
- 260 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Test product is compounded from cholic acid API on an individual basis dependent on the prescribed dosage.
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Amsterdam UMC Stichting
- Sponsor organisation
- Amsterdam UMC Stichting
- Address
- De Boelelaan 1117
- City
- Amsterdam
- Postcode
- 1081 HV
- Country
- Netherlands
Scientific contact point
- Organisation
- Amsterdam UMC Stichting
- Contact name
- Yasmin Polak
Public contact point
- Organisation
- Amsterdam UMC Stichting
- Contact name
- Yasmin Polak
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Ended | 8 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Amsterdam UMC Stichting
Internal medicine, Meibergdreef 9, 1105 AZ, Amsterdam
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 8 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2024-518652-23-00_Cholic Acid | 3.0 |
| Recruitment arrangements (for publication) | Please see section 10-2 Recruitment and consent of the protocol | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Cholic Acid adolescents 12 till 18 years | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Cholic Acid adults | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Cholic Acid children 6 till 12 years | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Cholic Acid parents or guardian or legal representative | 2.0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Kolbam 50 en 250 mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Orphacol 50 en 250 mg | 1 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-10-14 | Netherlands | Acceptable with conditions 2024-11-25
|
2024-11-25 |