Intracerebral hemorrhage (ICH) is a devastating form of cerebrovascular disease for which there are no approved therapeutics that improve outcomes. Apolipoprotein E (apoE) has emerged as a promising therapeutic target given its isoform-specific neuroprotective properties and ability to modulate neuroinflammatory responses. We developed a 5-amino acid peptide, CN-105, that mimics the polar face of the apoE helical domain involved in receptor interactions, readily crosses the blood-brain barrier, and improves outcomes in well-established preclinical ICH models. In the current study, aim to assess the safety and the efficacy of CN-105 after administration for three consecutive days in participants with acute supratentorial ICH at three different dosages.
Inclusion Patients with spontaneous acute supratentorial intracerebral hemorrhage confirmed by CT,age 30 to 80 years,Intravenous infusion with CN-105 peptide for injection every 6 hours, up to a maximum of 13 doses within 72 hours。 Blood samples for protein markers will be collected and detected at screening, 48 h(D3), and 120 h(D6) after the first dose: The sample size is 240.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
240
Injection every 6 hours, up to a maximum of 13 doses within 72 hours.Each dose of CN-105 will be administered as a slow IV bolus over 30 minutes.
Beijing Tiantan Hospital
Beijing, China
RECRUITINGAEs
Number and severity of AEs throughout the duration of the study;
Time frame: 90±7 days
SAEs
Number and severity of SAEs throughout the duration of the study;
Time frame: 90±7 days
Treatment-related mortality;
Treatment-related mortality throughout the duration of the study;
Time frame: 90±7 days
Deaths
Rate of mortality at 14-day, 30-day, and 90-day ;
Time frame: Day14, Day30,Day90
Incidence of cerebritis, meningitis, ventriculitis;
Incidence of cerebritis, meningitis, ventriculitis throughout the duration of the study;
Time frame: 90±7 days
Incidence of systemic infection associated with intracerebral hemorrhage
Incidence of systemic infection associated with intracerebral hemorrhage throughout the duration of the study;
Time frame: 90±7 days
The incidence of hematoma extension
The incidence of hematoma extension in 24-48 h after the first dose of study drug administration relative to baseline;
Time frame: 24-48 hour (Day2~Day3)
Modified Rankin Scale(mRS)
The proportion of patients alive and independent (mRS 0-2) on D90;
Time frame: Day90
National Institutes of Health Stroke Scale (NIHSS)
During dosing neurological deterioration, defined as an increase of National Institutes of National Institutes of Health Stroke Scale (NIHSS) \> 2 from baseline( unrelated to sedation);
Time frame: 90±7 days
contrast head CT to evaluate progression of perihematomal edema;
At screening, 24h (D2), 48h (D3) and 120h (D6) after the first dose and D14, non-contrast head CT to evaluate progression of perihematomal edema;
Time frame: screening, 24hour (Day2), 48hour (Day3) and 120hour (Day6),Day14
Modified Rankin Scale(mRS)
At D30 The proportion of patients alive and independent (mRS 0-2) and the distribution of mRS scores(shift analysis)at D30, D90;
Time frame: Day30
Glasgow Coma Scale (GCS)
Glasgow Coma Scale (GCS) assessment at D3, D14;
Time frame: Day3, Day14
Barthel Index assessment
Barthel Index assessment at D14, D30, D90;
Time frame: Day14, Day30, Day90
Montreal Cognitive Assessment (MoCA)
Montreal Cognitive Assessment (MoCA) Score at D2, D30;
Time frame: Day2, Day30
MRI to evaluate the severity of neuronal injury and determine the progression of perihematomal edema respectively ;
At screening, 48h (D3), 120h (D6) after the first dose of study drug, MRI to evaluate the severity of neuronal injury and determine the progression of perihematomal edema respectively ;
Time frame: screening, 48hour (Day3), 120hour (Day6)
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