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

NCT03168581 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: CATCH5R01FD005387-02
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 5

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

Conditions

Intracerebral Hemorrhage

Outcome Measures

Primary Outcomes (4)

• CN-105 safety assessment

  Number and severity of AEs throughout the duration of the study

  90 days

• Mortality

  Record In-hospital 30-day mortality

  30 days

• Mortality

  record 90-day mortality

  90 days

• 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 Outcomes (2)

• Improvement in 30-day mortality

  30 days

• Improvement in 30-day functional outcomes

  30 days

Other Outcomes (3)

• Exploratory CT to evaluate progression of edema

  30 days

• Exploratory MRI to evaluate progression of edema

  30 days

• Exploratory neuroinflammatory biomarker assessment to evaluate progression of edema

  90 days

Study Arms (1)

CN-105

EXPERIMENTAL

All eligible subjects will receive study drug, CN-105

Drug: CN-105

Interventions

CN-105 DRUG

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)

CN-105

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Is male or female, age 30 to 80 years, inclusive.
• Has a confirmed diagnosis of spontaneous supratentorial ICH.
• 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 an interpretable and measurable diagnostic CT scan.
• Has a Glasgow Coma Scale (GCS) score ≥ 5 on presentation
• Has a National Institutes of Health Stroke Scale (NIHSS) score ≥ 4.
• Has systolic BP (SBP) \< 200 mm Hg at enrollment.

You may not qualify if:

• Is pregnant or lactating.
• Has a temperature greater than 38.5°C at Screening.
• Has ICH resulting from trauma.
• Has infratentorial hemorrhage (any involvement of the midbrain or lower brainstem as demonstrated by radiograph or complete third nerve palsy).
• Has primary intraventricular hemorrhage deemed to be at high risk for obstructive hydrocephalus, or extra-axial (ie, subarachnoid or subdural) extension of hemorrhage.
• Has radiographic evidence of underlying tumor.
• Has an unstable mass or evolving intracerebral compartment syndrome.
• Has a ruptured aneurysm, arteriovenous malformation, or vascular anomaly.
• Has a platelet count \< 100,000/mL.
• Has an international normalized ratio (INR) \< 1.6 or irreversible coagulopathy either due to medical condition or detected before screening.
• In the opinion of the investigator is unstable and would benefit from supportive care rather than supportive care plus CN-105.
• In the opinion of the investigator has any contraindication to the planned study assessments, including CT and MRI.
• 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.
• Concomitant enrollment in another interventional study.

Sponsors & Collaborators

• AegisCN LLC: lead
• Duke Clinical Research Institute: collaborator
• PharPoint Research, Inc.: collaborator

Study Sites (5)

A.B. Chandler Medical Center-University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Duke University Health System

Durham, North Carolina, 27709, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27103, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

University of Virginia Health Systems

Charlottesville, Virginia, 22908, United States

Location

Related Publications (3)

• 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.

  PMID: 27990643 BACKGROUND

• 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.

  PMID: 27713572 BACKGROUND

• 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.

  PMID: 35562205 DERIVED

MeSH Terms

Conditions

Cerebral Hemorrhage

Interventions

apolipoprotein E mimetic peptide CN-105

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Michael L James, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2017
• First Posted: May 30, 2017
• Study Start: August 28, 2017
• Primary Completion: September 30, 2019
• Study Completion: January 25, 2020
• Last Updated: March 11, 2020

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)