Phase 2 Study of the Safety and Neuroprotective Capacity of Scp776 in Acute Ischemic Stroke

Study Overview
=================
Brief Summary
-----------------
A Randomized, Placebo-Controlled, Double-Blind, Multicenter Study of the Safety and Neuroprotective Capacity of Scp776 in Subjects Undergoing Endovascular Thrombectomy for Acute Ischemic Stroke

Detailed Description
-----------------
This is a Phase 2 randomized, placebo-controlled, double-blind study that will be conducted in 2 parts: sequential dose escalation in Part A, followed by dose expansion in Part B. In Part A, approximately 40 evaluable subjects will be assigned 1:1:2 overall to Cohort 1, Cohort 2 or placebo. Doses of scp776 will be tested sequentially in 2 cohorts, each in parallel with a volume-matched placebo randomized as 1:1 scp776:placebo within each cohort, to maintain the overall 1:1:2 ratio. Subjects will receive doses of either normal saline (placebo) or scp776, approximately 24 hours apart.

Official Title
-----------------
A Randomized, Placebo-Controlled, Double-Blind, Multicenter Study of the Safety and Neuroprotective Capacity of Scp776 in Subjects Undergoing Endovascular Thrombectomy for Acute Ischemic Stroke

Conditions
-----------------
Acute Ischemic Stroke (AIS)

Intervention / Treatment
-----------------
* Drug: Placebo
* Drug: scp776 (1.9 mg/kg)
* Drug: scp776 (3.8 mg/kg)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Aged 18 years or older. Body weight of less than 150 kg. AIS intended for immediate endovascular treatment. Disabling stroke defined as a baseline NIHSS ≥6 at the time of randomization. Confirmed symptomatic intracranial occlusion, based on qualifying imaging, at one or more of the following locations: intracranial carotid artery and/or M1 middle cerebral artery. Onset of AIS (last time subject seen well) to randomization is ≤16 hours. Intended endovascular treatment with an approved endovascular device. Exclusion Criteria: Evidence of acute intra-cerebral hemorrhage on qualifying imaging, per radiology lab manual. Poor/no collateral circulation. (e.g. collateral score of 0 or 1). ASPECT score of 0-4. Current AIS is being treated with IV thrombolytic therapy (eg, alteplase, tenecteplase), or the subject has received thrombolytic therapy within the previous 24 hours. Intent to use any endovascular thrombectomy device that is not FDA-approved. Planned use of intra-arterial thrombolytic therapy. Known severe contrast allergy or absolute contraindication to iodinated contrast preventing endovascular intervention. Clinical history, past imaging, or clinical judgment suggests that the intracranial occlusion is chronic or there is suspected intracranial dissection such that there is a predicted lack of success with endovascular intervention. Known arterial condition that would prevent the mechanical device from achieving reperfusion (eg, aortic dissection, carotid stent). Subjects with end-stage kidney disease. Subjects taking a chronic anticoagulant (eg, warfarin, apixaban). Known metastatic malignancy with poor prognosis. Subjects with any comorbid disease, condition, or situation that would confound the neurologic and functional evaluations, prevent improvement, or render the subject unable to complete follow-up treatment, in the opinion of the investigator. Participation in another clinical trial of an FDA-unapproved therapeutic device or drug in the 30 days preceding study inclusion. Subject has previously received scp776 in another clinical trial.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: This is a Phase 2 randomized, placebo-controlled, double-blind study that will be conducted in 2 parts: sequential dose escalation in Part A, followed by dose expansion in Part B. In Part A, approximately 40 evaluable subjects will be assigned 1:1:2 overall to Cohort 1, Cohort 2 or placebo. Doses of scp776 will be tested sequentially in 2 cohorts, each in parallel with a volume-matched placebo randomized as 1:1 scp776:placebo within each cohort, to maintain the overall 1:1:2 ratio. Subjects will receive doses of either normal saline (placebo) or scp776, approximately 24 hours apart. Cohort 1 dose regimen: - 1.9 mg/kg Cohort 2 dose regimen: 3.8 mg/kg The study will proceed into Part B (dose expansion), in which approximately 40 subjects will be randomized 1:1 to the chosen scp776 therapeutic dose from Part A or volume-matched placebo: Cohort 3: Therapeutic dose scp776:placebo
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Volume Matched Placebo (normal saline) | Drug: Placebo<br>* Volume Matched Placebo<br>|
| Experimental: scp776 (1.9 mg/kg)<br>Cohort 1 dose regimen: Intravenous (IV) slow injection(s) over 2 minutes - 1.9 mg/kg | Drug: scp776 (1.9 mg/kg)<br>* Cohort 1 dose regimen: Intravenous (IV) slow injection(s) over 2 minutes - 1.9 mg/kg<br>|
| Experimental: scp776 (3.8 mg/kg)<br>Cohort 2 dose regimen: Intravenous (IV) injection(s) over 2 minutes - 3.8 mg/kg | Drug: scp776 (3.8 mg/kg)<br>* Cohort 1 dose regimen: Intravenous (IV) slow injection(s) over 2 minutes - 3.8 mg/kg<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in NIHSS from baseline to Day 7 or at hospital discharge (whichever occurs first). | Change from baseline in NIHSS will be assessed with Analyses of Variance performed on the FAS and PPAS. Terms to be included in the model are baseline NIHSS, treatment, and ASPECT score (ASPECT score ≤6 versus ASPECT score >6). | Baseline to Day 7 or at hospital discharge (whichever occurs first). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in NIHSS from baseline to Day 3 |  | Baseline through Day 3 | 
| Change in Modified Rankin Scale score at Day 30 from baseline |  | Baseline through Day 30 | 
| Change in Modified Rankin Scale score at Day 90 from baseline |  | Baseline through Day 90 | 
| Change in NIHSS from baseline to Day 1 |  | Baseline through Day 1 | 
| Change in NIHSS from baseline to Day 2 |  | Baseline through Day 2 | 
| Change in Barthel Index score at Day 90 from baseline |  | Baseline through Day 90 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Stroke, Acute, Neuroprotectant