Complement Inhibition: Attacking the Overshooting Inflammation @Fter Subarachnoid Hemorrhage (CIAO@SAH)

NCT06359782 | Recruiting Phase 2 FDA Drug

• 1 other identifier: NL76082.058.20
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 1

Brief Summary

Aneurysmal subarachnoid hemorrhage (SAH) can lead to devastating outcomes for patients, like cognitive decline. This is caused by early brain injury (EBI) followed by delayed cerebral ischemia (DCI). Neuroinflammation, triggered by the complement system, has been investigated to be a key mediator in the pathophysiology of EBI and DCI. Inhibition of the complement system is therefore considered to be a potentially important new treatment for SAH. This trial aims 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

Subarachnoid Hemorrhage, Aneurysmal

Outcome Measures

Primary Outcomes (2)

• Number of participants with delayed cerebral ischemia (DCI)

  Defined as either a new focal neurological impairment, 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 by means of clinical assessment, CT or MRI scanning of the brain, and appropriate laboratory studies.

  To be determined between day 4 and day 14 of admission

• Number of participants with complications during hospitalization.

  Complication rate during hospitalization

  Up to 1 year after admission

Secondary Outcomes (13)

• Number of participants with cerebral infarction on brain CT

  at 14 days after admission

• Number of participants dying

  Up to 1 year after admission

• Neurological condition measured by Glasgow Coma Scale

  During the first 14 days

• Complement activity markers measured in serum and CSF

  Before IV administration of C1-INH or placebo, and after 48 hours and 96 hours after IV administration

• Inflammatory markers measured in serum and CSF

  Before IV administration of C1-INH or placebo, and after 48 hours and 96 hours after IV administration

Study Arms (2)

C1-esterase inhibitor (Cinryze)

EXPERIMENTAL

One group receiving study medication (C1-esterase inhibitor Cinryze)

Drug: C1 Esterase Inhibitor Injection [Cinryze]

Placebo

PLACEBO COMPARATOR

One group receiving placebo medication

Drug: Placebo

Interventions

C1 Esterase Inhibitor Injection [Cinryze] DRUG

C1 Esterase Inhibitor Injection \[Cinryze\]

Also known as: Cinryze

C1-esterase inhibitor (Cinryze)

Placebo DRUG

Sodium Chloride /physiological saline (0.9%) in equal volume dosed intravenous

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of aneurysmal subarachnoid hemorrhage on CT-scan;
• Age ≥ 18 years on admission;
• WFNS grade 1-5.

You may not qualify if:

• Subarachnoid hemorrhage deemed most likely of 'peri mesencephalic' origin after consideration of history, clinical examination and radiological findings (including angiographic imaging); (not originated from an aneurysm and patients have by definition a favourable clinical outcome)
• Subarachnoid hemorrhage deemed most likely of post-traumatic origin after consideration of history, clinical examination and radiological findings (including angiographic imaging); (does not occur spontaneous)
• 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;
• Pregnant woman

Sponsors & Collaborators

• Haaglanden Medical Centre: lead
• Leiden University Medical Center: collaborator
• Takeda: collaborator

Study Sites (1)

Haaglanden Medical Centre

The Hague, South Holland, 2512HH, Netherlands

RECRUITING

MeSH Terms

Conditions

Subarachnoid Hemorrhage

Interventions

Complement C1 Inhibitor Protein; SERPING1 protein, human

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Complement C1 Inactivator Proteins; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Complement Inactivator Proteins; Complement System Proteins; Immunoproteins; Blood Proteins; Proteins

Study Officials

• Wouter Moojen, MD PHD

  Haaglanden Medisch Centrum

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Daan de Groot, MD

CONTACT

088 979 7900; daan.de.groot@haaglandenmc.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: A prospective, multicenter, randomized, double-blind, placebo-controlled, phase II trial.

Study Record Dates

• First Submitted: March 22, 2024
• First Posted: April 11, 2024
• Study Start: November 4, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: December 27, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)