Evaluation of CN-105 in Subject With Acute Supratentorial Intracerebral Hemorrhage
Condition: Intracerebral Hemorrhage
MeSH terms: Cerebral Hemorrhage; Hemorrhage
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      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.

      The study is not powered to test any specific hypothesis in regard to safety and will instead
      use descriptive methods to describe the experience of the study cohort with respect to
      adverse and serious adverse events (SAEs), as well as the occurrence of several pre-specified
      events of interest. The secondary objective of this study will be met by comparing the
      modified Rankin score (mRS) at 30 days between participants treated with CN-105 with placebo
      controlled participants The mRS at 30 days will be compared between treated and control
      participants using the Wilcoxon rank sum test. Exploratory analyses include comparison of
      treated and control participants for radiographic cerebral edema and hematoma volume and
      expansion and biological markers of inflammation.

      Primary: To assess safety of CN-105 administration in primary ICH.

      Secondary: To evaluate whether the administration of CN-105 improves 30-day mortality and
      functional outcomes by comparing participants treated with CN-105 with placebo controlled
      participants.

      Exploratory:

        -  To investigate feasibility of Day 0, 1, 2, and 5 non-contrast head computed tomography
           (CT) as a radiographic surrogate to evaluate progression of perihematomal 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.Primary:

        -  Number and severity of AEs throughout the duration of the study

        -  Number and severity of SAEs throughout the duration of the study

        -  In-hospital, 30-day, and 90-day mortality

        -  Treatment-related mortality

        -  In-hospital neurological deterioration, defined as an increase of National Institutes of
           Health Stroke Scale (NIHSS), > 2 from baseline and/or decrease of > 2 of Glasgow Coma
           Scale (GCS), persisting more than 24 hours, and unrelated to sedation

        -  Incidence of cerebritis, meningitis, ventriculitis

        -  Incidence of systemic infection

        -  Incidence of hematoma extension Secondary:.

        -  30- and 90-day mRS

        -  Need for intracranial hypertension management

        -  NIHSS score, Glasgow Coma Scale, Montreal Cognitive Assessment, Stroke Impact Scale-16,
           and Barthel Index assessment at hospital discharge and 30 days after ICH

        -  Discharge disposition

      Exploratory:

        -  Day 0, 1, 2, 5 non-contrast head CT as a radiographic surrogate to evaluate progression
           of perihematomal edema

        -  Biochemical surrogates of brain injury, including plasma concentrations of S100B, glial
           fibrillary acidic protein, metalloproteinase-3 and -9, C-reactive protein, D-dimer,
           brain natriuretic peptide, interleukin-6, tumor necrosis factor-α, and vascular
           endothelial growth factor, assessed daily for 5 days after ICH or until discharge
           (concentration time area under the curve assessed for each biomarker)
    

Intervention name(s): Acetyl-Valine-Serine-Arginine-Arginine-Arginine-NH2 (Ac-VSRRR- NH2).; 0.9% Sodium-chloride
Intervention type(s): Drug; Drug
Intervention description(s): 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.; normal saline
Other intervention name(s): CN105
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The treatment arm will be given CN 105 The placebo arm will be give 0/9% NaCl
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Supportive Care