Study of the Safety and Neuroprotective Capacity of Scp776 in Acute Ischemic Stroke
- Conditions
- Acute Ischemic Stroke (AIS)
- Interventions
- Drug: scp776 (1.9 mg/kg)Drug: scp776 (3.8 mg/kg)Drug: scp776 (4.8 mg/kg)Drug: PlaceboDrug: scp776 (all dose levels)
- Registration Number
- NCT05585606
- Lead Sponsor
- Silver Creek Pharmaceuticals
- 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 60 evaluable subjects will be assigned 1:1:1:3 overall to Cohort 1, Cohort 2, Cohort 3, or placebo. Doses of scp776 will be tested sequentially in 3 cohorts, each in parallel with a volume-matched placebo randomized as 1:1 scp776:placebo within each cohort, to maintain the overall 1:1:1:3 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• Cohort 3 dose regimen:- 4.8 mg/kg
Upon completion of Part A, the study will proceed into Part B (dose expansion), in which approximately 40 subjects will be randomized 3:1 to the chosen scp776 therapeutic dose from Part A or volume-matched placebo.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 120
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Aged 18 years or older.
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Body weight of less than 150 kg.
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AIS intended for immediate endovascular treatment.
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Disabling stroke defined as a baseline NIHSS ≥6 at the time of randomization.
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Confirmed symptomatic intracranial occlusion, based on qualifying imaging, at one or more of the following locations: intracranial carotid artery and/or M1 or M2 middle cerebral artery.
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Onset of AIS (last time subject seen well) to randomization is ≤24 hours.
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Intended endovascular treatment with an approved endovascular device.
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Pre-AIS (24 hours before stroke onset) independent functional status in activities of daily living with Modified Rankin Scale score of 0, 1, or 2. Subject must be living in their own home, apartment, or seniors' lodge where no nursing care is required.
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Treating team and subject family are committed to full medical support for the subject.
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Signed informed consent from subject or legally authorized representative, if required to enable inclusion by applicable national laws and regulations and the applicable independent review boards/ethics committee requirements for obtaining consent. Electronic consent is allowed in jurisdictions wherein this consent process is allowed.
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Biologically female subjects must meet the following:
- Subject must be surgically sterile or be at least 1 year postmenopausal, OR
- Subjects of child-bearing potential must:
i. have a negative serum or urine pregnancy test at Screening, AND ii. have no plans to become pregnant or to breast feed during the study, AND iii. at least one of the following must apply:
- have a monogamous partner who is surgically sterile.
- have a monogamous same sex partner.
- be practicing abstinence or using an acceptable form of birth control while participating in the study through Day 90. Site personnel will provide instructions on what is an acceptable method.
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If male, unless the subject has a same sex partner, be either sterile (surgically or biologically), commit to an acceptable double barrier method of birth control, or practice abstinence, until at least 30 days after study drug administration. Site personnel will provide instructions on what is an acceptable method.
- Evidence of acute intra-cerebral hemorrhage on qualifying imaging, per radiology lab manual.
- Poor/no collateral circulation in the opinion of the investigator (e.g., collateral score of 0 or 1 if data available).
- ASPECT score of 0-4.
- Current AIS is being treated with IV thrombolytic therapy (e.g., alteplase, tenecteplase), or the subject has received thrombolytic therapy within the previous 24 hours.
- Intent to use any endovascular device that is not Food and Drug Administration (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 (e.g., aortic dissection, carotid stent).
- Subjects with end stage kidney disease.
- Part A Cohort 1: Subjects taking a chronic anticoagulant (e.g., apixaban, warfarin) are excluded. Chronic use of anti-platelet drugs is acceptable.
- Part A Cohort 2: Subjects taking a chronic anticoagulant (e.g., apixaban, warfarin) are excluded unless subject has both a STAT international normalized ratio (INR) < 1.7, and a platelet count > 100K/µL prior to randomization. Chronic use of anti-platelet drugs is acceptable.
- Part A Cohort 3 and Part B: With SRC approval, subjects in Part A Cohort 3 and Part B taking a chronic anticoagulant (e.g., apixaban, warfarin) are excluded unless subject has both a STAT international normalized ratio (INR) < 1.7, and a platelet count > 100K/µL prior to randomization.
(If the SRC does not approve expansion of this criterion, then subjects taking a chronic anticoagulant (e.g., apixaban, warfarin) are excluded, as in Cohort 1. Chronic use of anti-platelet drugs is acceptable in either case.)
- 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. Examples of excluded comorbid conditions include respiratory failure because of pneumonia, chronic diseases with significant disability, or non-ambulatory status. Contact medical monitor for consultation if necessary.
- Participation in another clinical trial of an FDA-unapproved therapeutic device or drug in the 30 days preceding study inclusion.
- Subject was a participant in either SCP CL 0001 or SCP CL 0002 and received scp776, or previously participated in SCP-CL-0003.
- Subject is experiencing moderate or severe hypotension as defined by CTCAE criteria (i.e., symptomatic and requiring medical intervention with fluid resuscitation and/or vasopressors) or a confirmed systolic blood pressure less than 90 mmHg.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description scp776 (1.9 mg/kg) scp776 (1.9 mg/kg) Cohort 1 dose regimen: Intravenous (IV) injection(s) over 2 minutes - 1.9 mg/kg scp776 (1.9 mg/kg) scp776 (all dose levels) Cohort 1 dose regimen: Intravenous (IV) injection(s) over 2 minutes - 1.9 mg/kg scp776 (3.8 mg/kg) scp776 (3.8 mg/kg) Cohort 2 dose regimen: Intravenous (IV) injection(s) over 2 minutes - 3.8 mg/kg scp776 (3.8 mg/kg) scp776 (all dose levels) Cohort 2 dose regimen: Intravenous (IV) injection(s) over 2 minutes - 3.8 mg/kg scp776 (4.8 mg/kg) scp776 (4.8 mg/kg) Cohort 3 dose regimen: Intravenous (IV) injection(s) over 2 minutes - 4.8 mg/kg scp776 (4.8 mg/kg) scp776 (all dose levels) Cohort 3 dose regimen: Intravenous (IV) injection(s) over 2 minutes - 4.8 mg/kg Placebo Placebo Volume Matched Placebo (normal saline)
- Primary Outcome Measures
Name Time Method Total number of SAEs recorded prior to hospital discharge Baseline to Day 7 or at hospital discharge (whichever occurs first). Generalized linear models will be fit assuming a Poisson family with log link. The regression model will include a term for the duration of hospitalization. The regression models may also be adjusted for any or all of the following utilizing a stepwise approach: Time from LKW or stroke onset to reperfusion; Reperfusion Status (eTICI score from central read); Age; and, ASPECTS (raw score from central read).
Proportion of subjects experiencing adverse events of special interest (AESIs) Baseline to Day 7 or at hospital discharge (whichever occurs first). Proportion of subjects experiencing adverse events of special interest (AESIs):
* Hypoglycemia
* Tachycardia
* Bleeding events:
* Symptomatic intracranial hemorrhage as per the central imaging review
* Asymptomatic intracranial hemorrhage as per the central imaging review
* Extracranial hemorrhage
- Secondary Outcome Measures
Name Time Method Modified Rankin Scale (mRS) Score Day 7 or discharge (whichever occurs first), Day 30, and Day 90. Assessment of disability after stroke using the Modified Rankin Scale, ranging from 0 (no disability) to 6 (death).
Infarct Volume by Central Imaging Review At 24 hours, and 72 - 96 hours or discharge (whichever occurs first). Infarct volume measured centrally via imaging (MRI or CT), evaluating ischemic lesion size.
All-cause Mortality By Day 30, and by Day 90. Incidence of death from any cause.
NIH Stroke Scale (NIHSS) Score at Day 7 / Discharge (whichever comes first) Baseline to Day 7 or at hospital discharge (whichever occurs first). NIH Stroke Scale score assessing neurological deficits and stroke severity. Scores range from 0 (no deficits) to 42 (severe deficits).
NIHSS at discharge will be analyzed using Analysis of Covariance (ANCOVA). Terms to be included in the model are age, baseline NIHSS, ASPECTS (from central review), eTICI (from central review), and treatment.NIH Stroke Scale (NIHSS) Score Daily from Days 1 through 7, Day 30, and Day 90. NIH Stroke Scale (NIHSS) score assessing neurological deficits and stroke severity. Scores range from 0 (no deficits) to 42 (severe deficits).
Trial Locations
- Locations (14)
HonorHealth Scottsdale Osborn Medical Center
🇺🇸Scottsdale, Arizona, United States
Marcus Neuroscience Institute
🇺🇸Boca Raton, Florida, United States
Augusta University Medical Center
🇺🇸Augusta, Georgia, United States
SSM Health DePaul Hospital
🇺🇸Bridgeton, Missouri, United States
St. Luke's Hospital of Kansas City
🇺🇸Kansas City, Missouri, United States
UNM Hospital
🇺🇸Albuquerque, New Mexico, United States
Northshore University Hospital
🇺🇸Manhasset, New York, United States
Lennox Hill Hospital
🇺🇸New York, New York, United States
The Ohio State University
🇺🇸Columbus, Ohio, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Oregon Stroke Center at OHSU
🇺🇸Portland, Oregon, United States
Providence St. Vincent Medical Center
🇺🇸West Haven-Sylvan, Oregon, United States
Jefferson Abington Hospital
🇺🇸Abington, Pennsylvania, United States
Houston Methodist Neurological Institute
🇺🇸Houston, Texas, United States