A Proof of Concept Study to Evaluate CN-105 in ICH Patients

Intracerebral Hemorrhage Clinical Trial

— CATCH  

Official title:

A Proof of Concept Study to Evaluate Administration of CN-105 in Patients With Acute Supratentorial Intracerebral Hemorrhage

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03168581
• Other study ID #: CATCH
• Secondary ID: 5R01FD005387-02
• Status: Completed
• Phase: Phase 2
• Start date: August 28, 2017
• Est. completion date: January 25, 2020

Study information

• Verified date: July 2019
• Source: AegisCN LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A multicenter, open-label phase 2a trial of CN-105 in patients with supratentorial intracerebral hemorrhage (ICH). Patients will be evaluated for eligibility within 12 hours of symptom onset. Eligible participants (approximately 60) will receive CN-105 administered intravenously (IV) for a 30-minute infusion every 6 hours for up to a maximum of 3 days (13 doses) or until discharge (if earlier than 3 days). Participants will be monitored daily throughout the Treatment phase of the study (up to a maximum of 5 days) and will receive standard-of-care treatment for the duration of the study. Additional protocol assessments will be required during the Treatment phase. After discharge from the hospital, participants will enter a 3-month Follow-up phase, with a clinic visit at 30 days and a follow-up telephone interview with telephone-validated Modified Rankin Scale (mRS) at 90 days after first dose of study agent.

Funding Source - FDA OOPD

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: January 25, 2020
• Est. primary completion date: September 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 80 Years

Eligibility

Inclusion Criteria:

1. 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).

2. Stated willingness to comply with all study procedures and availability for the duration of the study.

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

4. Has a confirmed diagnosis of spontaneous supratentorial ICH.

5. 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.

6. Has an interpretable and measurable diagnostic CT scan.

7. Has a Glasgow Coma Scale (GCS) score = 5 on presentation

8. Has a National Institutes of Health Stroke Scale (NIHSS) score = 4.

9. Has systolic BP (SBP) < 200 mm Hg at enrollment.

Exclusion Criteria:

1. Is pregnant or lactating.

2. Has a temperature greater than 38.5°C at Screening.

3. Has ICH resulting from trauma.

4. Has infratentorial hemorrhage (any involvement of the midbrain or lower brainstem as demonstrated by radiograph or complete third nerve palsy).

5. Has primary intraventricular hemorrhage deemed to be at high risk for obstructive hydrocephalus, or extra-axial (ie, subarachnoid or subdural) extension of hemorrhage.

6. Has radiographic evidence of underlying tumor.

7. Has an unstable mass or evolving intracerebral compartment syndrome.

8. Has a ruptured aneurysm, arteriovenous malformation, or vascular anomaly.

9. Has a platelet count < 100,000/mL.

10. Has an international normalized ratio (INR) < 1.6 or irreversible coagulopathy either due to medical condition or detected before screening.

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

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

13. Any condition which could interfere with, or the treatment for which might interfere with, the conduct of the study or which, in the opinion of the investigator, unacceptably increases the individual's risk by participating in the study.

14. Concomitant enrollment in another interventional study.

Related Conditions & MeSH terms

• Cerebral Hemorrhage
• Hemorrhage
• Intracerebral Hemorrhage

Intervention

Drug:
• CN-105
Patients with supratentorial intracerebral hemorrhage (ICH) will be evaluated for eligibility within 12 hours of symptom onset. Eligible participants will receive CN-105 administered intravenously (IV) for a 30 -minute infusion every 6 hours for up to a maximum of 3 days (13 doses) or until discharge (if earlier than 3 days)

Locations

Country	Name	City	State
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Virginia Health Systems	Charlottesville	Virginia
United States	Duke University Health System	Durham	North Carolina
United States	A.B. Chandler Medical Center-University of Kentucky	Lexington	Kentucky
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
AegisCN LLC	Duke Clinical Research Institute, PharPoint Research, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (2)

Guptill JT, Raja SM, Boakye-Agyeman F, Noveck R, Ramey S, Tu TM, Laskowitz DT. Phase 1 Randomized, Double-Blind, Placebo-Controlled Study to Determine the Safety, Tolerability, and Pharmacokinetics of a Single Escalating Dose and Repeated Doses of CN-105 in Healthy Adult Subjects. J Clin Pharmacol. 2017 Jun;57(6):770-776. doi: 10.1002/jcph.853. Epub 2016 Dec 19. — View Citation

Lei B, James ML, Liu J, Zhou G, Venkatraman TN, Lascola CD, Acheson SK, Dubois LG, Laskowitz DT, Wang H. Neuroprotective pentapeptide CN-105 improves functional and histological outcomes in a murine model of intracerebral hemorrhage. Sci Rep. 2016 Oct 7;6:34834. doi: 10.1038/srep34834. Erratum in: Sci Rep. 2017 Jan 05;7:39580. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory CT to evaluate progression of edema	To investigate feasibility of noncontrast head computed tomography (CT) as a radiographic surrogate to evaluate progression of perihematomal edema	30 days
Other	Exploratory MRI to evaluate progression of edema	To investigate feasibility magnetic resonance imaging (MRI) radiographic surrogate measures to evaluate progression of perihematomal edema	30 days
Other	Exploratory neuroinflammatory biomarker assessment to evaluate progression of edema	To investigate feasibility of using serial biochemical markers of neuroinflammation and neuronal injury as a surrogate measure of perihematomal edema and clinical outcome in the setting of spontaneous ICH	90 days
Primary	CN-105 safety assessment	Number and severity of AEs throughout the duration of the study	90 days
Primary	Mortality	Record In-hospital 30-day mortality	30 days
Primary	Mortality	record 90-day mortality	90 days
Primary	In-hospital neurological deterioration	Increase of National Institutes of Health Stroke Scale (NIHSS), > 2 from baseline, persisting more than 24 hours, and unrelated to sedation.	30 days
Secondary	Improvement in 30-day mortality	Compare participants treated with CN-105 with matched controls	30 days
Secondary	Improvement in 30-day functional outcomes	Compare participants treated with CN-105 with matched controls	30 days