Evaluation of CN-105 in Subject With Acute Supratentorial Intracerebral Hemorrhage

NCT03711903 | Completed Phase 2 DMC

• 1 other identifier: S-CATCH
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Phase 2, randomized, double-blind, placebo controlled study to evaluate the administration of CN-105 in patients with supratentorial intracerebral hemorrhage (ICH). Patients will be evaluated for eligibility within 12 hours of symptom onset. Eligible participants (30 active participants and 30 control participants) will receive CN-105 or placebo 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 as outlined in Section 7.5. 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 mRS at 90 days after first dose of study agent.

Conditions

Intracerebral Hemorrhage

Outcome Measures

Primary Outcomes (55)

• adverse event

  any untoward medical occurrence associated with the use of the drug in a participant

  0-12 hours

• adverse event

  untoward medical occurrence associated with the use of the study drug whether considered related or not

  24 hour

• adverse event

  untoward medical occurrence associated with the use of the study drug whether considered related or not

  48 hour

• adverse event

  untoward medical occurrence associated with the use of the study drug whether considered related or not

  72 hour

• adverse event

  untoward medical occurrence associated wtth the use of study drug whether considered related or not

  96 hour

• adverse event

  untoward medical occurrence associated wtth the use of study drug whether considered related or not

  120 hour

• adverse event

  untoward medical occurrence associated with the use of study drug whether considered related or not

  30 day

• adverse event

  untoward medical occurrence associated with the use of study drug whether considered related or not

  90 day

• GCS

  score as per scale

  0-12 hour

• GCS

  scored as per scale

  24H

• GCS

  scored as per scale

  48 hours

• GCS

  scored as per scale

  72 Hour

• GCS

  scored as per scale

  96 hour

• GCS

  scored as per scale

  at 120 hour

• GCS

  scored as per scale

  at 30 day

• NIHSS

  scored as per assessment

  0- 12 hour

• NIHSS

  scored as per assessment

  120 hour

• NIHSS

  scored as per assessment

  24 hour

• NIHSS

  scored as per assessment

  48 hour

• NIHSS

  scored as per assessment

  72 hour

• NIHSS

  scored as per assessment

  96 Hour

• NIHSS score

  score as per assessment

  30 day

• Serious adverse event

  An AE is considered serious if the investigator believes any of the following outcomes may occur: death, life threatening AE which places participants at immediate risk of death at the time of the event as it occurred, persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions; Congenital abnormality or birth defect ;Requires inpatient hospitalization or prolongation of existing hospitalization with the exception or preplanned (before the study) hospital admissions, planned admissions, hospitalization of less then 24 hours (after discharge from index hospitalization.

  48 hour

• Serious adverse event

  An AE is considered serious if the investigator believes any of the following outcomes may occur: death, life threatening AE which places participants at immediate risk of death at the time of the event as it occurred, persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions; Congenital abnormality or birth defect ;Requires inpatient hospitalization or prolongation of existing hospitalization with the exception or preplanned (before the study) hospital admissions, planned admissions, hospitalization of less then 24 hours (after discharge from index hospitalization.

  0-12 hour

• Serious adverse event

  An AE is considered serious if the investigator believes any of the following outcomes may occur: death, life threatening AE which places participants at immediate risk of death at the time of the event as it occurred, persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions; Congenital abnormality or birth defect ;Requires inpatient hospitalization or prolongation of existing hospitalization with the exception or preplanned (before the study) hospital admissions, planned admissions, hospitalization of less then 24 hours (after discharge from index hospitalization.

  72 hour

• Serious adverse event

  An AE is considered serious if the investigator believes any of the following outcomes may occur: death, life threatening AE which places participants at immediate risk of death at the time of the event as it occurred, persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions; Congenital abnormality or birth defect ;Requires inpatient hospitalization or prolongation of existing hospitalization with the exception or preplanned (before the study) hospital admissions, planned admissions, hospitalization of less then 24 hours (after discharge from index hospitalization.

  96 hour

• Serious adverse event

  An AE is considered serious if the investigator believes any of the following outcomes may occur: death, life threatening AE which places participants at immediate risk of death at the time of the event as it occurred, persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions; Congenital abnormality or birth defect ;Requires inpatient hospitalization or prolongation of existing hospitalization with the exception or preplanned (before the study) hospital admissions, planned admissions, hospitalization of less then 24 hours (after discharge from index hospitalization.

  at 90 day

• Serious adverse event

  An AE is considered serious if the investigator believes any of the following outcomes may occur: death, life threatening AE which places participants at immediate risk of death at the time of the event as it occurred, persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions; Congenital abnormality or birth defect ;Requires inpatient hospitalization or prolongation of existing hospitalization with the exception or preplanned (before the study) hospital admissions, planned admissions, hospitalization of less then 24 hours (after discharge from index hospitalization.

  at 120 hour

• Serious adverse event

  An AE is considered serious if the investigator believes any of the following outcomes may occur: death, life threatening AE which places participants at immediate risk of death at the time of the event as it occurred, persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions; Congenital abnormality or birth defect ;Requires inpatient hospitalization or prolongation of existing hospitalization with the exception or preplanned (before the study) hospital admissions, planned admissions, hospitalization of less then 24 hours (after discharge from index hospitalization.

  at 30 day

• systemic infection

  presence of any infection supported by clinical diagnosis, or any laboratory work up.

  0-12 hour

• systemic infection

  presence of any infection supported by clinical diagnosis, or any laboratory work up.

  24 hour

• systemic infection

  presence of any infection supported by clinical diagnosis, or any laboratory work up.

  48 hour

• systemic infection

  presence of any infection supported by clinical diagnosis, or any laboratory work up.

  72 hour

• systemic infection

  presence of any infection supported by clinical diagnosis, or any laboratory work up.

  96 hours

• systemic infection

  presence of any infection supported by clinical diagnosis, or any laboratory work up.

  120 hours

• systemic infection

  presence of any infection supported by clinical diagnosis, or any laboratory work up.

  30 day

• systemic infection

  presence of any infection supported by clinical diagnosis, or any laboratory work up.

  90 day

• Brain CT scan

  evaluate hematoma expansion

  0-12 hour

• Brain CT scan

  evaluate hematoma expansion

  24 Hour

• presence of CNS infection

  meningitis, cerebritis, ventriculitis

  24 hour

• presence of CNS infection

  meningitis, cerebritis, ventriculitis

  72 hours

• presence of CNS infection

  meningitis, cerebritis, ventriculitis

  0-12 hour

• presence of CNS infection

  meningitis, cerebritis, ventriculitis

  48 hours

• presence of CNS infection

  meningitis, cerebritis, ventriculitis

  120 hour

• presence of CNS infection

  meningitis, cerebritis, ventriculitis

  96 hour

• presence of CNS infection

  meningitis, cerebritis, ventriculitis

  30 day

• presence of CNS infection

  meningitis, cerebritis, ventriculitis

  90 day

• Mortality

  death related or unrelated to the study drug

  0-12 hour

• Mortality

  death related or unrelated to the study drug

  48 hour

• Mortality

  death related or unrelated to the study drug

  72 hour

• Mortality

  death related or unrelated to the study drug

  24 hour

• Mortality

  death related or unrelated to the study drug

  96 hour

• Mortality

  death related or unrelated to the study drug

  120 hour

• Mortality

  occurrence of death related or not related to the use of the study drug

  30- day

• Mortality

  occurrence of death related or not related to the use of the study drug

  90 -day

Secondary Outcomes (9)

• outcome as assessed by mRS

  120 hour

• functional outcome as assessed by mRS

  30 Day

• outcome as assessed by mRS

  90Day

• cognitive assessment

  120 Hour

• Discharge disposition

  day 90

Other Outcomes (6)

• biomarkers of brain injury

  0-12 hour

• biomarkers of brain injury

  24 hour

• biomarkers of brain injury

  48 hour

Study Arms (2)

Treatment arm

EXPERIMENTAL

The study drug, CN-105, will be administered at 1.0 mg/kg every 6 +/- 1 hour. The calculated volumes of study agent will be removed from the vials and transferred to 250 mL of normal saline (0.9% sodium chloride injection, USP). The recorded weight at baseline will be used to determine the appropriate amount of CN-105 drug product to administer. Estimated weight may be used if recorded weight is not available. Each dose of CN-105 or placebo will be administered as a slow IV bolus over 30 minutes.

Drug: Acetyl-Valine-Serine-Arginine-Arginine-Arginine-NH2 (Ac-VSRRR- NH2).

Placebo arm

PLACEBO COMPARATOR

The Placebo arm will be given 0.9% NaCL

Drug: 0.9% Sodium-chloride

Interventions

Acetyl-Valine-Serine-Arginine-Arginine-Arginine-NH2 (Ac-VSRRR- NH2). DRUG

The study drug, CN-105 is supplied in amber glass vials containing 4 mL of a concentrated 12.5-mg/mL clear-to-slightly-yellow solution.

Also known as: CN105

Treatment arm

0.9% Sodium-chloride DRUG

normal saline

Placebo arm

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 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:

• Known pregnancy and lactation 2.Has a temperature greater than 38.5°C at Screening. 3.ICH known to result from trauma. 4.Evidence of infratentorial hemorrhage (any involvement of the midbrain or lower brainstem as demonstrated by radiograph or complete third nerve palsy) severely limiting the recovery potential of the patient in the opinion of the investigator.
• Evidence of primary intraventricular hemorrhage deemed to be at high risk for obstructive hydrocephalus, in the opinion of the investigator or evidence of extra-axial (i.e., subarachnoid or subdural) extension of hemorrhage severely limiting the recovery potential of the patient in the opinion of the investigator.
• Radiographic evidence of underlying tumor. 7.Known unstable mass or active radiographic evidence and symptoms of herniation syndromes severely limiting the recovery potential of the patient in the opinion of the investigator.
• Known ruptured aneurysm, arteriovenous malformation, or vascular anomaly. 9.Has a platelet count \< 100,000/mL. 10.Has an international normalized ratio (INR) \> 1.5 or irreversible coagulopathy either due to medical condition or detected before screening.
• Is taking new oral anticoagulants (NOACS) 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.
• \. 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

• National Neuroscience Institute: lead
• AegisCN LLC: collaborator
• Singapore Clinical Research Institute: collaborator

Study Sites (1)

National Neuroscience Institute

Singapore, 308433, Singapore

Location

Related Publications (16)

• Li N, Liu YF, Ma L, Worthmann H, Wang YL, Wang YJ, Gao YP, Raab P, Dengler R, Weissenborn K, Zhao XQ. Association of molecular markers with perihematomal edema and clinical outcome in intracerebral hemorrhage. Stroke. 2013 Mar;44(3):658-63. doi: 10.1161/STROKEAHA.112.673590. Epub 2013 Feb 6.

  PMID: 23391772 BACKGROUND

• Lynch JR, Pineda JA, Morgan D, Zhang L, Warner DS, Benveniste H, Laskowitz DT. Apolipoprotein E affects the central nervous system response to injury and the development of cerebral edema. Ann Neurol. 2002 Jan;51(1):113-7. doi: 10.1002/ana.10098.

  PMID: 11782990 BACKGROUND

• Lynch JR, Wang H, Mace B, Leinenweber S, Warner DS, Bennett ER, Vitek MP, McKenna S, Laskowitz DT. A novel therapeutic derived from apolipoprotein E reduces brain inflammation and improves outcome after closed head injury. Exp Neurol. 2005 Mar;192(1):109-16. doi: 10.1016/j.expneurol.2004.11.014.

  PMID: 15698624 BACKGROUND

• Wang J, Dore S. Inflammation after intracerebral hemorrhage. J Cereb Blood Flow Metab. 2007 May;27(5):894-908. doi: 10.1038/sj.jcbfm.9600403. Epub 2006 Oct 11.

  PMID: 17033693 BACKGROUND

• Gao J, Wang H, Sheng H, Lynch JR, Warner DS, Durham L, Vitek MP, Laskowitz DT. A novel apoE-derived therapeutic reduces vasospasm and improves outcome in a murine model of subarachnoid hemorrhage. Neurocrit Care. 2006;4(1):25-31. doi: 10.1385/NCC:4:1:025.

  PMID: 16498192 BACKGROUND

• Aono M, Bennett ER, Kim KS, Lynch JR, Myers J, Pearlstein RD, Warner DS, Laskowitz DT. Protective effect of apolipoprotein E-mimetic peptides on N-methyl-D-aspartate excitotoxicity in primary rat neuronal-glial cell cultures. Neuroscience. 2003;116(2):437-45. doi: 10.1016/s0306-4522(02)00709-1.

  PMID: 12559098 BACKGROUND

• Gebel JM Jr, Jauch EC, Brott TG, Khoury J, Sauerbeck L, Salisbury S, Spilker J, Tomsick TA, Duldner J, Broderick JP. Relative edema volume is a predictor of outcome in patients with hyperacute spontaneous intracerebral hemorrhage. Stroke. 2002 Nov;33(11):2636-41. doi: 10.1161/01.str.0000035283.34109.ea.

  PMID: 12411654 BACKGROUND

• Carhuapoma JR, Barker PB, Hanley DF, Wang P, Beauchamp NJ. Human brain hemorrhage: quantification of perihematoma edema by use of diffusion-weighted MR imaging. AJNR Am J Neuroradiol. 2002 Sep;23(8):1322-6.

  PMID: 12223372 BACKGROUND

• 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 RESULT

• Laskowitz DT, Goel S, Bennett ER, Matthew WD. Apolipoprotein E suppresses glial cell secretion of TNF alpha. J Neuroimmunol. 1997 Jun;76(1-2):70-4. doi: 10.1016/s0165-5728(97)00021-0.

  PMID: 9184634 RESULT

• 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 RESULT

• Misra UK, Adlakha CL, Gawdi G, McMillian MK, Pizzo SV, Laskowitz DT. Apolipoprotein E and mimetic peptide initiate a calcium-dependent signaling response in macrophages. J Leukoc Biol. 2001 Oct;70(4):677-83.

  PMID: 11590206 RESULT

• Laskowitz DT, Wang H, Chen T, Lubkin DT, Cantillana V, Tu TM, Kernagis D, Zhou G, Macy G, Kolls BJ, Dawson HN. Neuroprotective pentapeptide CN-105 is associated with reduced sterile inflammation and improved functional outcomes in a traumatic brain injury murine model. Sci Rep. 2017 Apr 21;7:46461. doi: 10.1038/srep46461.

  PMID: 28429734 RESULT

• Laskowitz DT, Thekdi AD, Thekdi SD, Han SK, Myers JK, Pizzo SV, Bennett ER. Downregulation of microglial activation by apolipoprotein E and apoE-mimetic peptides. Exp Neurol. 2001 Jan;167(1):74-85. doi: 10.1006/exnr.2001.7541.

  PMID: 11161595 RESULT

• Laskowitz DT, Blessing R, Floyd J, White WD, Lynch JR. Panel of biomarkers predicts stroke. Ann N Y Acad Sci. 2005 Aug;1053:30. doi: 10.1196/annals.1344.051. No abstract available.

  PMID: 16179504 RESULT

• Lynch JR, Blessing R, White WD, Grocott HP, Newman MF, Laskowitz DT. Novel diagnostic test for acute stroke. Stroke. 2004 Jan;35(1):57-63. doi: 10.1161/01.STR.0000105927.62344.4C. Epub 2003 Dec 11.

  PMID: 14671250 RESULT

MeSH Terms

Conditions

Cerebral Hemorrhage

Interventions

Sodium Chloride

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

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The treatment arm will be given CN 105 The placebo arm will be give 0/9% NaCl

Study Record Dates

• First Submitted: September 28, 2018
• First Posted: October 19, 2018
• Study Start: March 24, 2019
• Primary Completion: June 16, 2022
• Study Completion: June 16, 2022
• Last Updated: December 1, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)