Clinical trial NCT03168581: A Proof of Concept Study to Evaluate CN-105 in ICH Patients
Official title: A Proof of Concept Study to Evaluate Administration of CN-105 in Patients With Acute Supratentorial Intracerebral Hemorrhage
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Intracerebral Hemorrhage
Lead sponsor: AegisCN LLC
Sponsor class: INDUSTRY
Collaborators: name: Duke Clinical Research Institute
name: PharPoint Research, Inc.
First posted: 2017-05-30
Enrollment: 38
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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


Eligibility criteria: 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.

Primary outcomes:
measure: CN-105 safety assessment
timeFrame: 90 days
measure: Mortality
timeFrame: 30 days
measure: Mortality
timeFrame: 90 days
measure: In-hospital neurological deterioration
timeFrame: 30 days
Secondary outcomes:
measure: Improvement in 30-day mortality
timeFrame: 30 days
measure: Improvement in 30-day functional outcomes
timeFrame: 30 days
Other outcomes:
measure: Exploratory CT to evaluate progression of edema
timeFrame: 30 days
measure: Exploratory MRI to evaluate progression of edema
timeFrame: 30 days
measure: Exploratory neuroinflammatory biomarker assessment to evaluate progression of edema
timeFrame: 90 days
Locations:
city: Lexington
country: United States
facility: A.B. Chandler Medical Center-University of Kentucky
state: Kentucky
city: Durham
country: United States
facility: Duke University Health System
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Charlottesville
country: United States
facility: University of Virginia Health Systems
state: Virginia
Study officials:
affiliation: Duke University
name: Michael L James, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
citation: Li S, Wangqin R, Meng X, Li H, Wang Y, Wang H, Laskowitz D, Chen X, Wang Y. Tolerability and Pharmacokinetics of Single Escalating and Repeated Doses of CN-105 in Healthy Participants. Clin Ther. 2022 May;44(5):744-754. doi: 10.1016/j.clinthera.2022.03.006. Epub 2022 May 11.