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

Silver Creek Pharmaceuticals

Status and phase: Enrolling; Phase 2

Conditions: Acute Ischemic Stroke (AIS)

Treatments: Drug: scp776 (3.8 mg/kg); Drug: scp776 (1.9 mg/kg); Drug: scp776 (all dose levels); Drug: scp776 (4.8 mg/kg); Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT05585606

SCP-CL-0003

Details and patient eligibility

About

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

Full 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.

Enrollment: 120 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Triple Blind

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120 participants in 4 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Volume Matched Placebo (normal saline)

Treatment:

Drug: Placebo

scp776 (1.9 mg/kg)

Experimental group

Description:

Cohort 1 dose regimen: Intravenous (IV) injection(s) over 2 minutes - 1.9 mg/kg

Treatment:

Drug: scp776 (all dose levels)

Drug: scp776 (1.9 mg/kg)

scp776 (3.8 mg/kg)

Experimental group

Description:

Cohort 2 dose regimen: Intravenous (IV) injection(s) over 2 minutes - 3.8 mg/kg

Treatment:

Drug: scp776 (all dose levels)

Drug: scp776 (3.8 mg/kg)

scp776 (4.8 mg/kg)

Experimental group

Description:

Cohort 3 dose regimen: Intravenous (IV) injection(s) over 2 minutes - 4.8 mg/kg

Treatment:

Drug: scp776 (all dose levels)

Drug: scp776 (4.8 mg/kg)