Clinical trial NCT03711903: Evaluation of CN-105 in Subject With Acute Supratentorial Intracerebral Hemorrhage
Official title: A Phase 2, Randomized, Double Blind, Placebo , Controlled Study To Evaluate The Administration of CN-105 In Participants With Acute Supratentorial Intracerebral Hemorrhage
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Intracerebral Hemorrhage
Lead sponsor: National Neuroscience Institute
Sponsor class: OTHER
Collaborators: name: AegisCN LLC
name: Singapore Clinical Research Institute
First posted: 2018-10-19
Enrollment: 60
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The treatment arm will be given CN 105 The placebo arm will be give 0/9% NaCl
Primary purpose: SUPPORTIVE_CARE

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.

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)

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 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:

1Known 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.

5.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.

6.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.

8.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.

11.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.

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

14.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.

15.Concomitant enrollment in another interventional study.

Primary outcomes:
measure: adverse event
timeFrame: 0-12 hours
measure: adverse event
timeFrame: 24 hour
measure: adverse event
timeFrame: 48 hour
measure: adverse event
timeFrame: 72 hour
measure: adverse event
timeFrame: 96 hour
measure: adverse event
timeFrame: 120 hour
measure: adverse event
timeFrame: 30 day
measure: adverse event
timeFrame: 90 day
measure: GCS
timeFrame: 0-12 hour
measure: GCS
timeFrame: 24H
measure: GCS
timeFrame: 48 hours
measure: GCS
timeFrame: 72 Hour
measure: GCS
timeFrame: 96 hour
measure: GCS
timeFrame: at 120 hour
measure: GCS
timeFrame: at 30 day
measure: NIHSS
timeFrame: 0- 12 hour
measure: NIHSS
timeFrame: 120 hour
measure: NIHSS
timeFrame: 24 hour
measure: NIHSS
timeFrame: 48 hour
measure: NIHSS
timeFrame: 72 hour
measure: NIHSS
timeFrame: 96 Hour
measure: NIHSS score
timeFrame: 30 day
measure: Serious adverse event
timeFrame: 48 hour
measure: Serious adverse event
timeFrame: 0-12 hour
measure: Serious adverse event
timeFrame: 72 hour
measure: Serious adverse event
timeFrame: 96 hour
measure: Serious adverse event
timeFrame: at 90 day
measure: Serious adverse event
timeFrame: at 120 hour
measure: Serious adverse event
timeFrame: at 30 day
measure: systemic infection
timeFrame: 0-12 hour
measure: systemic infection
timeFrame: 24 hour
measure: systemic infection
timeFrame: 48 hour
measure: systemic infection
timeFrame: 72 hour
measure: systemic infection
timeFrame: 96 hours
measure: systemic infection
timeFrame: 120 hours
measure: systemic infection
timeFrame: 30 day
measure: systemic infection
timeFrame: 90 day
measure: Brain CT scan
timeFrame: 0-12 hour
measure: Brain CT scan
timeFrame: 24 Hour
measure: presence of CNS infection
timeFrame: 24 hour
measure: presence of CNS infection
timeFrame: 72 hours
measure: presence of CNS infection
timeFrame: 0-12 hour
measure: presence of CNS infection
timeFrame: 48 hours
measure: presence of CNS infection
timeFrame: 120 hour
measure: presence of CNS infection
timeFrame: 96 hour
measure: presence of CNS infection
timeFrame: 30 day
measure: presence of CNS infection
timeFrame: 90 day
measure: Mortality
timeFrame: 0-12 hour
measure: Mortality
timeFrame: 48 hour
measure: Mortality
timeFrame: 72 hour
measure: Mortality
timeFrame: 24 hour
measure: Mortality
timeFrame: 96 hour
measure: Mortality
timeFrame: 120 hour
measure: Mortality
timeFrame: 30- day
measure: Mortality
timeFrame: 90 -day
Secondary outcomes:
measure: outcome as assessed by mRS
timeFrame: 120 hour
measure: functional outcome as assessed by mRS
timeFrame: 30 Day
measure: outcome as assessed by mRS
timeFrame: 90Day
measure: cognitive assessment
timeFrame: 120 Hour
measure: Discharge disposition
timeFrame: day 90
measure: cognitive assessment
timeFrame: 30 day
measure: Barthel index
timeFrame: 120 hour
measure: Barthel index
timeFrame: 30 day
measure: Barthel index
timeFrame: 90 day
Other outcomes:
measure: biomarkers of brain injury
timeFrame: 0-12 hour
measure: biomarkers of brain injury
timeFrame: 24 hour
measure: biomarkers of brain injury
timeFrame: 48 hour
measure: biomarkers of brain injury
timeFrame: 72 hour
measure: biomarkers of brain injury
timeFrame: 96 hour
measure: biomarkers of brain injury
timeFrame: 120 hour
Locations:
city: Singapore
country: Singapore
facility: National Neuroscience Institute
Study officials:
References:
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