Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruiting
Participants planned
75
Countries
1
Sites
3
Intracerebral haemorrhage
To determine the effect of high-dose versus low-dose anakinra compared to standard medical management on cerebral oedema development after spontaneous supratentorial intracerebral haemorrhage.
Key facts
- Sponsor
- Stichting Radboud universitair medisch centrum
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Nervous System Diseases [C10]
- Trial duration
- 28 Oct 2024 → ongoing
- Decision date (initial)
- 2024-10-28
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
External identifiers
- EU CT number
- 2024-517230-17-00
- EudraCT number
- 2021-000324-36
- ClinicalTrials.gov
- NCT04834388
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy
To determine the effect of high-dose versus low-dose anakinra compared to standard medical management on cerebral oedema development after spontaneous supratentorial intracerebral haemorrhage.
Conditions and MedDRA coding
Intracerebral haemorrhage
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 5
- Age ≥ 18 years;
- Supratentorial non-traumatic ICH confirmed by CT, without a confirmed causative lesion on admission CT-angiography (e.g. aneurysm, AVM, DAVF, cerebral venous sinus thrombosis) or other known underlying lesion (e.g. tumour, cavernoma);
- Minimal intracerebral haemorrhage volume of 10 mL
- Intervention can be started within 8 hours from symptoms onset;
- Patient's or legal representative's informed consent.
Exclusion criteria 15
- Severe ICH, unlikely to survive the first 72 hours (defined as Glasgow Coma Scale score < 6 at time of consent);
- Confirmed or suspected haemorrhagic transformation of an arterial or venous infarct;
- Planned neurosurgical haematoma evacuation;
- Severe infection at admission, requiring antibiotic treatment;
- Known active tuberculosis or active hepatitis;
- Use of immunosuppressive or immune-modulating therapy at admission;
- Neutropenia (Absolute Neutrophil Count (ANC) <1.5 x 109/L );
- Pre-stroke modified Rankin Scale score ≥ 3;
- Pregnancy or breast-feeding;
- Standard contraindications to MRI;
- Known prior allergic reaction to gadolinium contrast or one of the constituents of its solution for administration;
- Known allergy to anakinra or other products that are produced by DNA technology using the micro-organism E. coli;
- Live vaccinations within the last 10 days prior to this ICH;
- Severe renal impairment (eGFR <30ml/min/1.73m);
- Known active malignancy
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Oedema extension distance (OED) determined with MRI
Secondary endpoints 4
- (serious) Adverse events
- Serum inflammatory markers IL-1β, IL-6, hsCRP, neutrophil and total white blood cell counts
- DCE-MRI measurement of BBB transfer constant (Ktrans)
- mRS, Barthel index and EQ-5D-5L score
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
SCP183367 · ATC
- Active substance
- Anakinra
- Route of administration
- INJECTION
- Max daily dose
- 2 mg/kg/h milligram(s)/kilogram/hour
- Max total dose
- 2 mg/kg/h milligram(s)/kilogram/hour
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- L04AC03 — ANAKINRA
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Subcutaneous solution is diluted in sodiumchloride to obtain an intravenous solution.
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Stichting Radboud universitair medisch centrum
- Sponsor organisation
- Stichting Radboud universitair medisch centrum
- Address
- Geert Grooteplein Zuid 10
- City
- Nijmegen
- Postcode
- 6525 GA
- Country
- Netherlands
Scientific contact point
- Organisation
- Stichting Radboud universitair medisch centrum
- Contact name
- Maaike Cliteur
Public contact point
- Organisation
- Stichting Radboud universitair medisch centrum
- Contact name
- Maaike Cliteur
Locations
1 EU/EEA country · 3 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Ongoing, recruiting | 75 | 3 |
| Rest of world | — | 0 | — |
Investigational sites
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 |
|---|---|---|---|---|---|
| Netherlands | 2024-10-28 | 2024-10-28 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Serious breaches 2 · Art. 52 CTR
Serious breach SB-67328
- Sponsor became aware
- 2025-01-08
- Date of breach
- 2024-12-29
- Submission date
- 2025-01-21
- Member states concerned
- Netherlands
- Categories
- Protocol
- Areas impacted
- Data reliability or robustness
- Benefit-risk balance changed
- No
- Description
- Patient was randomised for low-dose subcutaneous treatment, with a planned dosage of 6 times 100 mg s.c. Did only receive 5 subcutaneous dosages, the sixth was not administered due to an early stopping date/time on the digital prescription. This did not impact the rest of the study protocol, MRI and clinical follow up were obtained as planned.
- Sponsor actions
- The pharmacy department placed an extra notification in digital prescription system that total planned dosage is 6 injections to instruct the nurses. The prescription discripancy was evaluated with the physician involved
| Organisation | City | Country | Type |
|---|---|---|---|
| Isala Klinieken Stichting | Zwolle | Netherlands | Clinical investigator |
Serious breach SB-57472
- Sponsor became aware
- 2024-11-11
- Date of breach
- 2024-11-10
- Submission date
- 2024-11-15
- Member states concerned
- Netherlands
- Categories
- Protocol
- Areas impacted
- Other
- Benefit-risk balance changed
- No
- Description
- Screen failure:
Patient was randomised ater checking all inclusion and exclusion criteria. Written informed consent was provided. However, shortly after randomisation additional information on the CT-angiography became available and a underlying vascular malformation was found. This is an exclusion criterion.
No study procedures were performed, and treatment was not started. The patient is excluded from the study and will be replaced as described in the study protocol. - Sponsor actions
- Inclusion process have been evaluated with the physician involved and the clinical Neurology staff at the Isala Hospital will be retrained on the in- and exclusion criteria in this study by the local head investigator.
| Organisation | City | Country | Type |
|---|---|---|---|
| Isala Klinieken Stichting | Zwolle | Netherlands | Clinical investigator |
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 2024-517230-17-00_redacted | 5 |
| Recruitment arrangements (for publication) | K1_blank_document_Recruitment_arrangements | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF capacitated subjects ACTION | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF capacitated subjects RICH Biobank | 1.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF incapacitated subjects ACTION | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF incapacitated subjects RICH Biobank | 1.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF later capacitated subjects ACTION | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | SMPC anakinra current version | 2 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-10-03 | Netherlands | Acceptable 2024-10-28
|
2024-10-28 |