Study of the Safety and Neuroprotective Capacity of Scp776 in Acute Ischemic Stroke (ARPEGGIO)

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

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

Study Overview

• Status: Completed
• Conditions: Acute Ischemic Stroke (AIS)
• Intervention / Treatment: Drug: Placebo; Drug: scp776 (1.9 mg/kg); Drug: scp776 (all dose levels); Drug: scp776 (3.8 mg/kg); Drug: scp776 (4.8 mg/kg)

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.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85251
      • HonorHealth Scottsdale Osborn Medical Center
    • Tucson, Arizona, United States, 85719
      • Banner University Medical Center /Univ of Arizona
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Hartford Hospital
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Marcus Neuroscience Institute
    • Miami, Florida, United States, 33136
      • University of Miami - Jackson Memorial Hospital
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University Medical Center
  • Missouri
    • Bridgeton, Missouri, United States, 63044
      • SSM Health DePaul Hospital
    • Kansas City, Missouri, United States, 64111
      • St. Luke's Hospital of Kansas City
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • UNM Hospital
  • New York
    • Manhasset, New York, United States, 11030
      • Northshore University Hospital
    • New York, New York, United States, 10075
      • Lennox Hill Hospital
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
    • Toledo, Ohio, United States, 43608
      • Mercy Health - St Vincent Medical Center
    • Youngstown, Ohio, United States, 44504
      • Mercy Health - St Elizabeth Youngstown Hospital
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97239
      • Oregon Stroke Center at OHSU
    • West Haven-Sylvan, Oregon, United States, 97225
      • Providence St. Vincent Medical Center
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Jefferson Abington Hospital
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Health - M.S. Hershey Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Neurological Institute
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin and Froedtert Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 or M2 middle cerebral artery.
• Onset of AIS (last time subject seen well) to randomization is ≤24 hours.
• Intended endovascular treatment with an approved endovascular device.
• 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.
• Treating team and subject family are committed to full medical support for the subject.
• 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.

• Biologically female subjects must meet the following:

  1. Subject must be surgically sterile or be at least 1 year postmenopausal, OR
  2. 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:

  1. have a monogamous partner who is surgically sterile.
  2. have a monogamous same sex partner.
  3. 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.
• 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.

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Volume Matched Placebo (normal saline)	Drug: Placebo; Volume Matched Placebo
Experimental: scp776 (3.8 mg/kg); Cohort 2 dose regimen: Intravenous (IV) injection(s) over 2 minutes - 3.8 mg/kg	Drug: scp776 (all dose levels); A composite group encompassing all participants who received any dose level of the investigational drug under evaluation.; Drug: scp776 (3.8 mg/kg); Cohort 2 dose regimen: Intravenous (IV) slow injection(s) over 2 minutes - 3.8 mg/kg
Experimental: scp776 (1.9 mg/kg); Cohort 1 dose regimen: Intravenous (IV) injection(s) over 2 minutes - 1.9 mg/kg	Drug: scp776 (1.9 mg/kg); Cohort 1 dose regimen: Intravenous (IV) slow injection(s) over 2 minutes - 1.9 mg/kg; Drug: scp776 (all dose levels); A composite group encompassing all participants who received any dose level of the investigational drug under evaluation.
Experimental: scp776 (4.8 mg/kg); Cohort 3 dose regimen: Intravenous (IV) injection(s) over 2 minutes - 4.8 mg/kg	Drug: scp776 (all dose levels); A composite group encompassing all participants who received any dose level of the investigational drug under evaluation.; Drug: scp776 (4.8 mg/kg); Cohort 3 dose regimen: Intravenous (IV) slow injection(s) over 2 minutes - 4.8 mg/kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total number of SAEs recorded prior to hospital discharge	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).	Baseline to Day 7 or at hospital discharge (whichever occurs first).
Proportion of subjects experiencing adverse events of special interest (AESIs)	Proportion of subjects experiencing adverse events of special interest (AESIs): Hypoglycemia; Tachycardia; Bleeding events:Symptomatic intracranial hemorrhage as per the central imaging reviewAsymptomatic intracranial hemorrhage as per the central imaging reviewExtracranial hemorrhage	Baseline to Day 7 or at hospital discharge (whichever occurs first).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NIH Stroke Scale (NIHSS) Score	NIH Stroke Scale (NIHSS) score assessing neurological deficits and stroke severity. Scores range from 0 (no deficits) to 42 (severe deficits).	Daily from Days 1 through 7, Day 30, and Day 90.
Modified Rankin Scale (mRS) Score	Assessment of disability after stroke using the Modified Rankin Scale, ranging from 0 (no disability) to 6 (death).	Day 7 or discharge (whichever occurs first), Day 30, and Day 90.
Infarct Volume by Central Imaging Review	Infarct volume measured centrally via imaging (MRI or CT), evaluating ischemic lesion size.	At 24 hours, and 72 - 96 hours or discharge (whichever occurs first).
All-cause Mortality	Incidence of death from any cause.	By Day 30, and by Day 90.
NIH Stroke Scale (NIHSS) Score at Day 7 / Discharge (whichever comes 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, reperfusion status (TICI-based reperfusion grade), and treatment.	Baseline to Day 7 or at hospital discharge (whichever occurs first).

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Hospitalization	Number of consecutive days of inpatient hospitalization following the qualifying acute ischemic stroke.	Baseline to Day 90 or at hospital discharge (whichever occurs first).
Barthel Index Score at Day 90	Assessment of functional independence in activities of daily living (ADL). Scores range from 0 (complete dependence) to 100 (complete independence).	Day 90.
Proportion of Patients Achieving Barthel Index Score ≥90	Percentage of patients achieving Barthel Index scores of 90-100, indicating minimal or no dependence in daily living activities.	Day 90.
Exploratory Pharmacodynamics (PD) of Scp776 in this Population	Evaluation of exploratory pharmacodynamic effect via blood glucose area under the concentration-time curve (glucose AUC).	Multiple post-dose timepoints up to 72 hours.
Area Under the Concentration-Time Curve of Scp776	Pharmacokinetic parameter assessed using noncompartmental methods following intravenous administration of scp776 - area under the concentration time curve from time 0 to the last observed non-zero concentration (AUC0-t).	Pre-dose and multiple post-dose timepoints up to Day 30.
Extrapolated Area Under the Concentration-Time Curve of Scp776	Pharmacokinetic parameter assessed using noncompartmental methods following intravenous administration of scp776 - area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-inf).	Pre-dose and multiple post-dose timepoints up to Day 30.
Serum Concentration at End of Injection of Scp776	Pharmacokinetic parameter assessed using noncompartmental methods following intravenous administration of scp776 - serum drug concentration at the end of injection (Ceoi).	Pre-dose and multiple post-dose timepoints up to Day 30.
Volume of Distribution of Scp776	Pharmacokinetic parameter assessed using noncompartmental methods following intravenous administration of scp776 - apparent volume of distribution during the terminal elimination phase (Vz).	Pre-dose and multiple post-dose timepoints up to Day 30.
Total Serum Clearance of Scp776	Pharmacokinetic parameter assessed using noncompartmental methods following intravenous administration of scp776 - apparent total serum clearance after intravenous (IV) administration (CL).	Pre-dose and multiple post-dose timepoints up to Day 30.
Elimination Rate Constant of Scp776	Pharmacokinetic parameter assessed using noncompartmental methods following intravenous administration of scp776 - apparent first order terminal elimination rate constant (Kel).	Pre-dose and multiple post-dose timepoints up to Day 30.
Elimination Half-Life of Scp776	Pharmacokinetic parameter assessed using noncompartmental methods following intravenous administration of scp776 - apparent first order terminal elimination half-life (t½).	Pre-dose and multiple post-dose timepoints up to Day 30.
Maximum Observed Concentration of Scp776	Pharmacokinetic parameter assessed using noncompartmental methods following intravenous administration of scp776 - Maximum observed concentration (Cmax).	Pre-dose and multiple post-dose timepoints up to Day 30.
Immunogenicity Evaluation of Scp776	Evaluation of anti-drug antibody (ADA) formation in response to scp776 treatment. Presence of ADA measured at specified timepoints.	Pre-dose and multiple post-dose timepoints up to study completion (approximately Day 90).

Collaborators and Investigators

• Sponsor: Silver Creek Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2022
• Primary Completion (Actual): September 15, 2025
• Study Completion (Actual): September 15, 2025

Study Registration Dates

• First Submitted: October 14, 2022
• First Submitted That Met QC Criteria: October 14, 2022
• First Posted (Actual): October 19, 2022

Study Record Updates

• Last Update Posted (Actual): February 24, 2026
• Last Update Submitted That Met QC Criteria: February 20, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Stroke, Acute; Neuroprotectant
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Ischemic Stroke; Stroke; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: SCP-CL-0003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No