Efficacy and Safety of SP-8203 in Patients With Ischemic Stroke Requiring rtPA
Efficacy and Safety of SP-8203 in Patients With Ischemic Stroke Requiring rtPA
This clinical trial is designed to evaluate the efficacy and safety of the combination
 therapy of SP-8203 (Otaplimastat) and recombinant tissue Plasminogen Activator (rtPA)
 standard of care. In this clinical trial, rtPA will be injected intravenously using an
 infusion device. If reperfusion is not occur in spite of rtPA therapy, endovascular therapy
 can be performed.
This clinical trial is designed to evaluate the efficacy and safety of the combination
 therapy of SP-8203 and rtPA in patients with acute ischemic stroke receiving rtPA standard of
 care.

 As the standard procedure of rtPA therapy, rtPA will be injected intravenously using an
 infusion device. When reperfusion is not achieved in spite of rtPA therapy, endovascular
 therapy can be performed according to the judgment of a site investigator.

 A total of 178 subjects will be enrolled in double-blind, randomized and parallel design with
 89 subjects assigned to 80 mg/day SP-8203 group or placebo group, respectively.

 If a subject, who is able to be enrolled, has neurologic deficit of ≥4 point on the National
 Institute of Health Stroke Scale (NIHSS) score and give his/her consent to participate in the
 trial, each treatment is administered after the investigational product is randomly assigned
 by institution after sequential allocation. The randomization number of patients is the same
 as the assigned number of the investigational product administered to the patients. The
 subject will receive the Investigational products a total of 6 times, with 12 hours
 intervals. Only for the patients who consent, blood sample will be taken after the sixth
 administration of the Investigational product for pharmacokinetic and pharmacodynamics
 analysis. For pharmacokinetic profile analysis, blood sample will be taken at 0~5, 30±5, and
 120±5 minutes after the complete sixth administration of the investigational products. For
 pharmacodynamic profile analysis, blood sample will be taken at between 24 to 48 hours after
 the first administration, at 0 minute after the sixth administration and at 4th week visit.
 The first blood sampling time is set to after 24 hours because of the patient's stability,
 but it can be performed before the investigational product has been administered in
 accordance with the judgment of the investigators.

 The subject will have brain initial Magnetic Resonance Imaging (MRI) and Magnetic Resonance
 Angiography (MRA) performed within 6 hours before and after the administration of
 investigational product, and brain Computed Tomography (CT) will be performed at 24±3 hours
 after completion of the first administration of investigational products.

 Brain MRI and MRA will be followed-up on Day 5, and additionally the subject will make a
 visit for close monitoring for his/her neurologic condition at 4th week and 12th week.
 Thereafter, all the procedures of the clinical trial will be completed.

 When unexpected serious adverse reaction occurs during the clinical trial, the safety of
 subjects who participated in clinical trial and the clinical trial itself is objectively
 validated through the convocation and evaluation by Data Safety Monitoring Board (DSMB).
Inclusion Criteria:

 -  Patients with neurologic deficit of ≥ 4 points by NIHSS score

 -  Adults aged ≥19 years and ≤85 years. (Pre-stroke mRS must be 0 or 1; No significant
 pre-stroke disability)

 -  Subjects who can receive rtPA therapy within 4.5 hours after the onset of early
 symptoms of acute ischemic stroke.

 -  Subjects available for brain MRI (DWI, GRE/Susceptibility Weighted Imaging (SWI),
 FLAIR, MRA) scanning

 -  Subjects who consent to participate in this trial.

 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 age can participate in
 the trial only when non-pregnancy is confirmed. Woman of childbearing age 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 during the trial
 period.

 -  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 trial according to the judgment of
 investigators.

 -  Those who cannot be administered with rtPA.