A Study Evaluating the Safety and Efficacy of Neuroprotective Peptide CN-105 Peptide in Patients With Acute Supratentorial Intracerebral Hemorrhage

Intracerebral Hemorrhage Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06255977
• Other study ID #: PR-CBT-2019040-2F
• Status: Recruiting
• Phase: Phase 2
• Start date: August 24, 2022
• Est. completion date: August 2024

Study information

• Verified date: February 2024
• Source: Beijing Tiantan Hospital
• Contact: yongjun Wang, Study Director
• Phone: 13911172565
• Email: yongjunwang111[@]aliyun.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: August 2024
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Is male or female, age 30 to 80 years, inclusive;

2. Has a confirmed diagnosis of spontaneous supratentorial ICH by CT;

3. 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;

4. Has a GCS score = 8 at enrollment;

5. Has an NIHSS score = 6

6. Has Systolic BP (SBP) < 200 mmHg

7. 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:

1. Is pregnant or lactating;

2. Has a temperature greater than 38.5? at Screening;

3. The amount of intracerebral hemorrhage< 5 mL( coniglobus formula)

4. ICH known to result from trauma;

5. Primary intraventricular hemorrhage;

6. Radiographic evidence of underlying brain tumor;

7. 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);

8. 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;

9. Known ruptured cerebral aneurysm, arteriovenous malformation, or vascular anomaly; hemorrhage from cerebral infarction, cerebral venous sinus embolization;

10. Has a platelet count < 100×109/L,(INR) > 1.5 or irreversible coagulopathy either due to medical condition or detected before screening;

11. Is taking new oral anticoagulants (such as dabigatran etexilate, rivaroxaban, apixaban, etc.) or low molecular weight heparin at the time of ICH onset;

12. In the opinion of the investigator is unstable and would benefit from supportive care rather than supportive care plus CN-105;

13. In the opinion of the investigator has any contraindication to the planned study assessments, including CT and MRI;

14. Severe renal insufficiency: creatinine clearance <30 mL/ min (Cockcroft-Gault formula), urea nitrogen and/or serum creatinine >1.5×ULN;

15. Is scheduled for surgical intervention throughout the trial period dose, including but not limited to hematoma evacuation (including minimally invasive and routine surgery), decompressive craniectomy, hematoma aspiration;

16. Clinically significant history of cardiovascular disease, including; (1) congestive heart failure (NYHA Class > 2); (2) unstable angina; (3) myocardial infarction in the past 12 months; (4) any need for treatment or interventional supraventricular arrhythmia or ventricular arrhythmia;

17. Has electrocardiogram (ECG) examination abnormalities deemed clinically significant by the investigator: for example, QTc interval prolongation during screening (male > 450 ms, female > 470 ms) (Note: QTc interval must be calculated according to Fridericia's criteria);

18. Subjects were disabled before disease onset (mRS = 2)

19. Patients with past intracranial hemorrhage such as cerebral hemorrhage, subarachnoid hemorrhage, or cerebral infarction/transient ischemic attack (TIA, but excluding lucunar infarction);

20. Patients have other serious/severe acute or chronic mental illnesses, including recent (within the past 1 year) or current suicidal ideations or behaviors;

21. May increase the risks associated with participating in research or study drug management, or may interfere with the results of the study, or may interfere with the investigator's interpretation of laboratory abnormalities;

22. Patients are employees of the research center or family members directly related to the participants of this study, or subordinates who are not directly related to the trial but are subordinates of the trial, or are employed by the sponsor directly related to the trial;

23. Is predisposed to allergy or known allergy to any ingredient in the study drug;

24. Patients who have participated in other clinical trials or are participating in another interventional clinical study within 3 months prior to enrollment;

25. For other reasons, the investigator considered the subjects are inappropriate to be enrolled in the trial.

Related Conditions & MeSH terms

• Cerebral Hemorrhage
• Hemorrhage
• Intracerebral Hemorrhage

Intervention

Drug:
• CN-105
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.

Locations

Country	Name	City	State
China	Beijing Tiantan Hospital	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Beijing Tiantan Hospital	SDM Bio Service Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Biomarker Outcome Measures:	Biomarker analysis at screening, 48 h(D3), and 120 h(D6) after the first dose:Cytokines and chemokines: G-CSF, GM-CSF, IFN-?, IL-1a, IL-1ß, IL-1ra, IL-6, IL-17A, IP-10/CXCL10, MCP-1/CCL2, MIP-1a/CCL3, TNF-a, VEGF-A; Molecular markers associated with the nervous system: ApoE, GFAP;	screening, 48 hour(Day3), and 120 hour(Day6)
Other	Genetic marker	Genotyping at screening:1ApoE gene polymorphism analysis;2SNP analysis of TOMM40-APOE locus	screening
Primary	AEs	Number and severity of AEs throughout the duration of the study;	90±7 days
Primary	SAEs	Number and severity of SAEs throughout the duration of the study;	90±7 days
Primary	Treatment-related mortality;	Treatment-related mortality throughout the duration of the study;	90±7 days
Primary	Deaths	Rate of mortality at 14-day, 30-day, and 90-day ;	Day14, Day30,Day90
Primary	Incidence of cerebritis, meningitis, ventriculitis;	Incidence of cerebritis, meningitis, ventriculitis throughout the duration of the study;	90±7 days
Primary	Incidence of systemic infection associated with intracerebral hemorrhage	Incidence of systemic infection associated with intracerebral hemorrhage throughout the duration of the study;	90±7 days
Primary	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;	24-48 hour (Day2~Day3)
Secondary	Modified Rankin Scale(mRS)	The proportion of patients alive and independent (mRS 0-2) on D90;	Day90
Secondary	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);	90±7 days
Secondary	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;	screening, 24hour (Day2), 48hour (Day3) and 120hour (Day6),Day14
Secondary	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;	Day30
Secondary	Glasgow Coma Scale (GCS)	Glasgow Coma Scale (GCS) assessment at D3, D14;	Day3, Day14
Secondary	Barthel Index assessment	Barthel Index assessment at D14, D30, D90;	Day14, Day30, Day90
Secondary	Montreal Cognitive Assessment (MoCA)	Montreal Cognitive Assessment (MoCA) Score at D2, D30;	Day2, Day30
Secondary	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 ;	screening, 48hour (Day3), 120hour (Day6)