Efficacy and Safety of SP-8203 (Otaplimastat) in Patients With Acute Ischemic Stroke Receiving Thrombolytic Standard of Care (SP-8203-3001)

A Multi-Center, Randomized, Double-Blind, Parallel, Placebo-Controlled, Phase III Clinical Study to Evaluate Efficacy and Safety of SP-8203 (Otaplimastat) in Patients With Acute Ischemic Stroke Requiring Thrombolytic Therapy as Standard of Care

This clinical study is designed to evaluate the efficacy and safety of the combination therapy of SP-8203 (otaplimastat) and thrombolytic standard of care in acute ischemic stroke patient.

As a standard of care, thrombolytic therapy (for instance, recombinant tissue plasminogen activator) will be administered. When reperfusion is not achieved in spite of thrombolytic therapy, endovascular therapy can be performed.

Study Overview

• Status: Recruiting
• Conditions: Ischemic Stroke
• Intervention / Treatment: Drug: SP-8203; Drug: Placebo

Detailed Description

Intravenous administration of SP-8203 (otaplimastat), a multipotent neuroprotectant inhibiting matrix metalloprotease activity, significantly reduced infarct volume and recombinant tissue plasminogen activator (rtPA)/ ischemic-induced damage in animal models.

This clinical study is designed to evaluate the efficacy and safety of the combination therapy of SP-8203 (otaplimastat) and thrombolytic standard of care in acute ischemic stroke patient.

As a standard of care, thrombolytic therapy (for instance, recombinant tissue plasminogen activator) will be administered. When reperfusion is not achieved in spite of thrombolytic therapy, endovascular therapy can be performed.

A total of 852 participants will be enrolled in double-blind, randomized and parallel design with 426 participants assigned to 80 mg/day SP-8203 arm or placebo arm, respectively.

Eligible participants are the patients with neurologic deficit of ≥8 point on National Institute of Health Stroke Scale (NIHSS) score. The participant will receive the study intervention a total of 6 times, with 12 hours intervals. Imaging test will be performed using validated machine and method. The participant will have initial brain Magnetic Resonance Imaging (MRI) and Magnetic Resonance Angiography (MRA) performed within 6 hours before or after the administration of study intervention, and brain Computed Tomography (CT) will be performed at 24±3 hours after completion of the first administration of study intervention.

Brain Magnetic Resonance Imaging (MRI) and Magnetic Resonance Angiography (MRA) will be followed-up on Day 5, and additionally the participant will undergo additional functional and neurological evaluations for up to 90 days.

When unexpected serious adverse reaction occurs during the clinical study, Data Safety Monitoring Board (DSMB) will be convened to validation safety.

• Study Type: Interventional
• Enrollment (Estimated): 852
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jong Sung Kim, MD, Phd; Phone Number: +82-33-610-3114; Email: jongskim@amc.seoul.kr
• Study Contact Backup: Name: Byung Su Kim, MS; Phone Number: +82-70-5168-6503; Email: 135kbs@shinpoong.co.kr

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of, 49201
    • Recruiting
    • Dong-A University Hospital
    • Contact: Neurology; Phone Number: +82-31348-9354; Email: 135kbs@shinpoong.co.kr
  • Ulsan, Korea, Republic of, 44033
    • Recruiting
    • Ulsan University Hospital
    • Contact: Neurology; Phone Number: +82-31348-9354; Email: 135kbs@shinpoong.co.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with neurologic deficit of ≥ 8 points by National Institute of Health Stroke Scale (NIHSS) score
• Patients with pre-stroke modified Rankin Scale (mRS) must be 0 or 1, which means they were able to carry out all usual duties and activities
• Adults aged ≥19 years and ≤85 years
• Patients who can receive thrombolytic standard of care within 4.5 hours after the onset of early symptoms of acute ischemic stroke
• Patients available for brain Magnetic Resonance Imaging (MRI) scanning
• Patients who consent to participate in this study

Exclusion Criteria:

• Patients with systemic allergic diseases or hypersensitivity to specific drugs.
• Patients who were diagnosed with myocardial infarction (MI) within the last 6 months.
• Patients who had arrhythmia causing clinical symptoms such as dyspnea or palpitation within the last 6 months.

• Patients showing the following abnormal ECG findings in stable condition at Emergency Room:

  • The range of pulse rate - under 55/min or exceed 120/min
  • 2nd or 3rd degree Atrioventricular (AV) block indicated in ECG
  • Congenital or acquired QT syndrome indicated in ECG
  • Pre-excitation syndrome indicated in ECG
• Patients with severe heart failure of New York Heart Association (NYHA) Class III or Class IV.
• Patients with fever (≥ 38℃) or infection signs which require antibiotic therapy at screening.
• Patients with pulmonary diseases (asthma, Chronic Obstruction Pulmonary disease, and active tuberculosis etc.) who have being recently been treated more than 1 month at screening.
• Patients with decreased hemoglobin (Hb< 10g/dL), decreased platelet count (PLT< 100,000/mm3) or hematocrit of <25% in complete blood count.
• Patients who have undergone hemodialysis and/or treatments due to nephropathies, acute or chronic renal failure at screening.
• Patients with a cancer in following conditions: diagnosed within 6 months before the screening time, or any treatment for cancer within the previous 6 months, or with recurrent/ metastatic cancer.
• Pregnant and lactating women. However, Women of Childbearing Potential (WOCBP) can participate in the study only when non-pregnancy is confirmed. Women of Childbearing Potential (WOCBP) is defined as woman who is not definitely menopause and did not receive a surgical contraception.
• Patients who do not consent to use double barrier contraception until 90 days from the first study intervention administration.
• Patients who have participated in other clinical trials of other drugs within the past 3 months. However, if they participated in observational studies and did not take drugs, they can participate in this trial.
• Patients who cannot participate in the study at the discretion of investigators
• Patients who are unable to receive thrombolytic standard of care, rtPA

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SP-8203; SP-8203 80 mg (40 mg/dose twice a day for three days)	Drug: SP-8203; SP-8203 80 mg will be intravenously administered as 40 mg/dose twice daily (intervals of 12 hours); Other Names: Otaplimastat (SP-8203)
Placebo Comparator: Placebo; Placebo group: twice a day for three days	Drug: Placebo; Placebo will be intravenously administered twice daily (intervals of 12 hours)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with modified Rankin Scale (mRS) 0-1	Proportion of participants with modified Rankin Scale (mRS) 0-1 at Day 90 in patients with acute ischemic stroke requiring thrombolytic standard of care	Day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of parenchymal hematoma observed on brain Computed Tomography (CT) scan	Incidence of parenchymal hematoma observed on brain Computed Tomography (CT) scan performed at 24±3 hours in accordance with European Cooperative Acute Stroke Study (ECASS) I and II criteria, after the administration of SP-8203 in conjunction with thrombolytic standard of care	Day 1
Proportion of participants with modified Rankin Scale (mRS) 0-1	Proportion of participants with modified Rankin Scale (mRS) 0-1 at Day 30 in patients with acute ischemic stroke requiring thrombolytic standard of care	Day 30
Proportion of participants with modified Rankin Scale (mRS) 0-2	Proportion of participants with modified Rankin Scale (mRS) 0-2 at Day 30 and Day 90 in the patients with acute ischemic stroke requiring thrombolytic standard of care	Day 30 and Day 90
Change from Baseline in National Institute of Health Stroke Scale (NIHSS) scores	The change in the National Institute of Health Stroke Scale (NIHSS) scores until 90 day in subjects with acute ischemic stroke requiring rtPA standard of care. The maximum total score is 42 points, which indicates the most critical condition and the minimum total score is 0, which indicates no neurologic deficit.	Day 0 (baseline), Day 3, Day 5, Day 30 and Day 90
Fold change in infarct growth classified by modified treatment in cerebral ischemia (mTICI) grade within 5 days	MRI (DWI) imaging outcomes	Day 5
The incidence of serious adverse events	The incidence of serious adverse events	follow-up to 90 days after the first study intervention administration
The rate of death	The rate of death due to any cause	follow-up to 90 days after the first study intervention administration
The incidence rate of adverse events, and adverse drug reaction	The incidence rate of adverse events, and adverse drug reaction	follow-up to 90 days after the first study intervention administration
The incidence of symptomatic Intracranial Hemorrhage (sICH)	The incidence of symptomatic Intracranial Hemorrhage (sICH) occurring within 5 days of administration according to the definition described on the protocol	within 5 days from the first study intervention administration
The Incidence of major systemic bleeding	The Incidence of major systemic bleeding according to the International Society of Thrombosis and Hemostasis (ISTH) definition	within 5 days after the first study intervention administration

Collaborators and Investigators

• Sponsor: Shin Poong Pharmaceutical Co. Ltd.
• Investigators: Study Chair: Jong Sung Kim, MD, Phd, Gangneung Asan Medical Center; Principal Investigator: Beom Jun Kim, MD, Phd, Seoul Asan Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2025
• Primary Completion (Estimated): March 30, 2027
• Study Completion (Estimated): March 30, 2027

Study Registration Dates

• First Submitted: October 25, 2024
• First Submitted That Met QC Criteria: October 25, 2024
• First Posted (Actual): October 28, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 4, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Thrombolytic therapy; SP-8203 (Otaplimastat); rtPA (recombinant tissue Plasminogen Activator)
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Brain Infarction; Brain Ischemia; Infarction; Necrosis; Ischemic Stroke; Stroke; Cerebral Infarction; Ischemia; Physiological Effects of Drugs; Protective Agents; Neuroprotective Agents; Otaplimastat
• Other Study ID Numbers: SP-8203-3001

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