Clinical trial NCT05585606: Study of the Safety and Neuroprotective Capacity of Scp776 in Acute Ischemic Stroke
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Ischemic Stroke (AIS)
Keywords: Stroke, Acute
Neuroprotectant
Lead sponsor: Silver Creek Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2022-10-19
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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 60 evaluable subjects will be assigned 1:1:1:3 overall to Cohort 1, Cohort 2, Cohort3, 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

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:

Cohort 3: Therapeutic dose scp776:placebo
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
measure: Total number of SAEs recorded prior to hospital discharge
timeFrame: Baseline to Day 7 or at hospital discharge (whichever occurs first).
measure: Proportion of subjects experiencing adverse events of special interest (AESIs)
timeFrame: Baseline to Day 7 or at hospital discharge (whichever occurs first).
Secondary outcomes:
measure: NIH Stroke Scale (NIHSS) Score at Day 7 / Discharge (whichever comes first)
timeFrame: Baseline to Day 7 or at hospital discharge (whichever occurs first).
measure: NIH Stroke Scale (NIHSS) Score
timeFrame: Daily from Days 1 through 7, Day 30, and Day 90.
measure: Modified Rankin Scale (mRS) Score
timeFrame: Day 7 or discharge (whichever occurs first), Day 30, and Day 90.
measure: Infarct Volume by Central Imaging Review
timeFrame: At 24 hours, and 72 - 96 hours or discharge (whichever occurs first).
measure: All-cause Mortality
timeFrame: By Day 30, and by Day 90.
Other outcomes:
measure: Duration of Hospitalization
timeFrame: Baseline to Day 90 or at hospital discharge (whichever occurs first).
measure: Barthel Index Score at Day 90
timeFrame: Day 90.
measure: Proportion of Patients Achieving Barthel Index Score ≥90
timeFrame: Day 90.
measure: Exploratory Pharmacodynamics (PD) of Scp776 in this Population
timeFrame: Multiple post-dose timepoints up to 72 hours.
measure: Area Under the Concentration-Time Curve of Scp776
timeFrame: Pre-dose and multiple post-dose timepoints up to Day 30.
measure: Extrapolated Area Under the Concentration-Time Curve of Scp776
timeFrame: Pre-dose and multiple post-dose timepoints up to Day 30.
measure: Serum Concentration at End of Injection of Scp776
timeFrame: Pre-dose and multiple post-dose timepoints up to Day 30.
measure: Volume of Distribution of Scp776
timeFrame: Pre-dose and multiple post-dose timepoints up to Day 30.
measure: Total Serum Clearance of Scp776
timeFrame: Pre-dose and multiple post-dose timepoints up to Day 30.
measure: Elimination Rate Constant of Scp776
timeFrame: Pre-dose and multiple post-dose timepoints up to Day 30.
measure: Elimination Half-Life of Scp776
timeFrame: Pre-dose and multiple post-dose timepoints up to Day 30.
measure: Maximum Observed Concentration of Scp776
timeFrame: Pre-dose and multiple post-dose timepoints up to Day 30.
measure: Immunogenicity Evaluation of Scp776
timeFrame: Pre-dose and multiple post-dose timepoints up to study completion (approximately Day 90).
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Scottsdale Osborn Medical Center
state: Arizona
city: Boca Raton
country: United States
facility: Marcus Neuroscience Institute
state: Florida
city: Augusta
country: United States
facility: Augusta University Medical Center
state: Georgia
city: Bridgeton
country: United States
facility: SSM Health DePaul Hospital
state: Missouri
city: Kansas City
country: United States
facility: St. Luke's Hospital of Kansas City
state: Missouri
city: Albuquerque
country: United States
facility: UNM Hospital
state: New Mexico
city: Manhasset
country: United States
facility: Northshore University Hospital
state: New York
city: New York
country: United States
facility: Lennox Hill Hospital
state: New York
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: Oregon Stroke Center at OHSU
state: Oregon
city: West Haven-Sylvan
country: United States
facility: Providence St. Vincent Medical Center
state: Oregon
city: Abington
country: United States
facility: Jefferson Abington Hospital
state: Pennsylvania
city: Houston
country: United States
facility: Houston Methodist Neurological Institute
state: Texas
Study officials:
References: