Overview
Sponsor-declared trial summary
aneurysmal subarachnoid hemorrhage
To study the safety and efficacy of C1-inhibitor Cinryze, an approved inhibitor of the complement system, compared to placebo in patients with SAH. By temporarily blocking the complement system we hypothesize limitation of delayed cerebral ischemia and a more favourable clinical outcome for SAH patients due to a decrea…
Key facts
- Sponsor
- Haaglanden Medisch Centrum Stichting
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Nervous System Diseases [C10]
- Decision date (initial)
- 2025-01-27
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Takeda Pharmaceuticals · Sint Jacobusstichting Stichting Haaglanden Medisch Centrum
External identifiers
- EU CT number
- 2025-520540-15-00
- EudraCT number
- 2020-005731-67
- ClinicalTrials.gov
- NCT06359782
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Safety
To study the safety and efficacy of C1-inhibitor Cinryze, an approved inhibitor of the complement system, compared to placebo in patients with SAH. By temporarily blocking the complement system we hypothesize limitation of delayed cerebral ischemia and a more favourable clinical outcome for SAH patients due to a decrease in the inflammatory response.
Conditions and MedDRA coding
aneurysmal subarachnoid hemorrhage
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- Confirmed diagnosis of aneurysmal subarachnoid hemorrhage on CT-scan
- Age of 18 years or above
- WFNS grade 1-5
Exclusion criteria 8
- Subarachnoid hemorrhage deemed most likely of peri mesencephalic origin after consideration of history, clinical examination and radiological findings (including angiographic imaging)
- Subarachnoid hemorrhage deemed most likely of post-traumatic origin after consideration of history, clinical examination and radiological findings (including angiographic imaging)
- Participation in another clinical therapeutic study
- Patients with definite infaust prognosis on arrival and/or expected death within 24 hours of admission
- Patients with a known hereditary complement deficiency (including hereditary angioedema)
- Patients with a history of sensibility to blood products or C1-inhibitor
- Patients with a know history of thrombosis (when known at time of inclusion)
- Pregnant women
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 2
- Number of participants with delayed cerebral ischemia (DCI). Defined as either a new focal neurological impariment, or a decrease of at least 2 points on the Glasgow Coma Scale. This should last for at least 1 hour, is not apparent immediately after aneurysm occlusion, and cannot be attributed to other causes bij means of clinical assessment, CT or MRI scanning of the brain, and appropriate laboratory studies
- Number of participants with complications during hospitalization
Secondary endpoints 7
- Cerebral infarction on brain CT at 14 days
- Mortality
- Daily neurological condition measured bij GCS during the first 14 days
- Complement activity in serum and CSF
- Coagulation cascade activation
- ICU length of stay
- Ventilator days
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Cinryze 500 IU powder and solvent for solution for injection
PRD3536225 · Product
- Active substance
- C1 Esterase Inhibitor (Human)
- Substance synonyms
- C1 INHIBITOR (HUMAN), Human C1-esterase inhibitor, C1-ESTERASE INHIBITOR, HUMAN
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- IV INFUSION
- Max daily dose
- 6000 IU international unit(s)
- Max total dose
- 6000 IU international unit(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B06AC01 — -
- Marketing authorisation
- EU/1/11/688/001
- MA holder
- TAKEDA MANUFACTURING AUSTRIA AG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 1
Sodium Chloride 0.9% w/v Intravenous Infusion BP Solution for Infusion.
PRD11819610 · Product
- Active substance
- Sodium Chloride
- Substance synonyms
- SODIUM CHLORID
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 6 mmol/kg millimole(s)/kilogram
- Max total dose
- 6 mmol/kg millimole(s)/kilogram
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B05BB01 — ELECTROLYTES
- Marketing authorisation
- PA0736/003/001
- MA holder
- B.BRAUN MELSUNGEN AG
- MA country
- Ireland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Haaglanden Medisch Centrum Stichting
- Sponsor organisation
- Haaglanden Medisch Centrum Stichting
- Address
- Lijnbaan 32
- City
- 'S-Gravenhage
- Postcode
- 2512 VA
- Country
- Netherlands
Scientific contact point
- Organisation
- Haaglanden Medisch Centrum Stichting
- Contact name
- Clinical trial information desk
Public contact point
- Organisation
- Haaglanden Medisch Centrum Stichting
- Contact name
- Clinical trial information desk
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Authorised, recruitment pending | 128 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
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) | D1_Protocol 2025-520540-15-00 | 3 |
| Recruitment arrangements (for publication) | Blanco | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Follow-up | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF patient | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF representative | 3 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Cinryze | 1 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2025-01-16 | Netherlands | Acceptable 2025-01-27
|
2025-01-27 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-03-09 | Netherlands | Acceptable 2025-01-27
|
2025-03-09 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2026-02-01 | Netherlands | Acceptable 2025-01-27
|
2026-02-01 |