A Multicenter, Randomized, Blind, Placebo-controlled, Dose-finding Phase II Trial Evaluating the Safety and Efficacy of the Neuroprotective Peptide CN-105 in Patients With Acute Supratentorial Intracerebral Hemorrhage (CN-CATCH)
Overview
- Phase
- Phase 2
- Intervention
- CN-105
- Conditions
- Intracerebral Hemorrhage
- Sponsor
- Beijing Tiantan Hospital
- Enrollment
- 240
- Locations
- 1
- Primary Endpoint
- AEs
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Is male or female, age 30 to 80 years, inclusive;
- •Has a confirmed diagnosis of spontaneous supratentorial ICH by CT;
- •Able to receive first dose of study drug ≤ 12 hours after onset of ICH symptoms, such as alteration in level of consciousness, severe headache, nausea, vomiting, seizure, and/or focal neurological deficits, or last-known well time;
- •Has a GCS score ≥ 8 at enrollment;
- •Has an NIHSS score ≥ 6
- •Has Systolic BP (SBP) \< 200 mmHg
- •Has given written informed consent to participate in the study in accordance with required regulations; if a participant is not capable of providing informed consent, written consent must be obtained from the participant's legally authorized representative (LAR).
Exclusion Criteria
- •Is pregnant or lactating;
- •Has a temperature greater than 38.5℃ at Screening;
- •The amount of intracerebral hemorrhage\< 5 mL（ coniglobus formula）
- •ICH known to result from trauma;
- •Primary intraventricular hemorrhage；
- •Radiographic evidence of underlying brain tumor;
- •Patients with a history of malignant tumor (non-melanoma in situ skin cancer that has achieved complete remission after treatment and has not relapsed in the past 5 years or other types eligible for inclusion in the opinion of the investigator);
- •Known unstable mass or active radiographic evidence and symptoms of herniation severely limiting the recovery potential of the patient in the opinion of the investigator;
- •Known ruptured cerebral aneurysm, arteriovenous malformation, or vascular anomaly; hemorrhage from cerebral infarction, cerebral venous sinus embolization;
- •Has a platelet count \< 100×109/L，(INR) \> 1.5 or irreversible coagulopathy either due to medical condition or detected before screening;
Arms & Interventions
Placebo Control: placebo
Intravenous infusion with placebo（same volume of saline） every 6 hours, up to a maximum of 13 doses within 72 hours.Each dose of placebo（same volume of saline） will be administered as a slow IV bolus over 30 minutes.
Intervention: CN-105
Experimental: CN-105 peptide for injection 0.1 mg/kg
Intravenous infusion with 0.1 mg/kg CN-105 peptide for 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.
Intervention: CN-105
Experimental:CN-105 peptide for injection 0.3 mg/kg
Intravenous infusion with 0.3 mg/kg CN-105 peptide for 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.
Intervention: CN-105
Experimental: CN-105 peptide for injection 1.0 mg/kg
Intravenous infusion with 1.0 mg/kg CN-105 peptide for 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.
Intervention: CN-105
Outcomes
Primary Outcomes
AEs
Time Frame: 90±7 days
Number and severity of AEs throughout the duration of the study;
SAEs
Time Frame: 90±7 days
Number and severity of SAEs throughout the duration of the study;
Treatment-related mortality;
Time Frame: 90±7 days
Treatment-related mortality throughout the duration of the study;
Deaths
Time Frame: Day14, Day30,Day90
Rate of mortality at 14-day, 30-day, and 90-day ;
Incidence of cerebritis, meningitis, ventriculitis;
Time Frame: 90±7 days
Incidence of cerebritis, meningitis, ventriculitis throughout the duration of the study;
The incidence of hematoma extension
Time Frame: 24-48 hour （Day2~Day3）
The incidence of hematoma extension in 24-48 h after the first dose of study drug administration relative to baseline；
Incidence of systemic infection associated with intracerebral hemorrhage
Time Frame: 90±7 days
Incidence of systemic infection associated with intracerebral hemorrhage throughout the duration of the study;
Secondary Outcomes
- Modified Rankin Scale(mRS)(Day30)
- National Institutes of Health Stroke Scale (NIHSS)(90±7 days)
- contrast head CT to evaluate progression of perihematomal edema;(screening, 24hour (Day2), 48hour (Day3) and 120hour (Day6),Day14)
- Barthel Index assessment(Day14, Day30, Day90)
- MRI to evaluate the severity of neuronal injury and determine the progression of perihematomal edema respectively ；(screening, 48hour (Day3), 120hour (Day6))
- Glasgow Coma Scale (GCS)(Day3, Day14)
- Montreal Cognitive Assessment (MoCA)(Day2, Day30)