A Phase 2, Randomized, Double Blind, Placebo , Controlled Study To Evaluate The Administration of CN-105 In Participants With Acute Supratentorial Intracerebral Hemorrhage
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- NIHSS
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 30 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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-
- •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.
研究组 & 干预措施
Placebo arm
The Placebo arm will be given 0.9% NaCL
干预措施: 0.9% Sodium-chloride (Drug)
Treatment arm
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.
干预措施: Acetyl-Valine-Serine-Arginine-Arginine-Arginine-NH2 (Ac-VSRRR- NH2). (Drug)
结局指标
主要结局
NIHSS
时间窗: 96 Hour
scored as per assessment
Brain CT scan
时间窗: 24 Hour
evaluate hematoma expansion
GCS
时间窗: at 30 day
scored as per scale
presence of CNS infection
时间窗: 90 day
meningitis, cerebritis, ventriculitis
NIHSS score
时间窗: 30 day
score as per assessment
adverse event
时间窗: 90 day
untoward medical occurrence associated with the use of study drug whether considered related or not
Mortality
时间窗: 90 -day
occurrence of death related or not related to the use of the study drug
Serious adverse event
时间窗: at 30 day
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.
systemic infection
时间窗: 90 day
presence of any infection supported by clinical diagnosis, or any laboratory work up.
次要结局
- functional outcome as assessed by mRS(30 Day)
- cognitive assessment(30 day)
- Discharge disposition(day 90)
- Barthel index(90 day)
- outcome as assessed by mRS(90Day)