Safety and Efficacy of Two Doses of SP-8203 in Patients With Ischemic Stroke Requiring rtPA
Condition: Ischemic Stroke
MeSH terms: Stroke; Ischemic Stroke; Cerebral Infarction; Ischemia
Study type: Interventional
Phase: Phase 2

Summary: 
      The current study aims to evaluate the safety of SP-8203, designing in two stages (stage-1,
      stage-2) to evaluate the safety and efficacy of the combination therapy of SP-8203 and rtPA
      for the occurrence of cerebral hemorrhage in patients with acute ischemic stroke receiving
      rtPA standard of care.
    

Detailed description: 
      As the standard procedure of rtPA therapy, rtPA will be injected intravenously using a device
      like infusion pump. When reperfusion is not achieved in spite of rtPA therapy, endovascular
      therapy can be performed according to the judgment of a site investigator.

      Stage 1-The trial will be conducted with 11 subjects participating in an open label design
      manner. Subjects with neurologic deficit of ≥4 point and ≤10 points on NIHSS score will be
      given SP-8203, 80mg/dose, a total of 6 times at intervals of 12 hours. For the first
      administration of SP-8203, it should be administered within 30 minutes from the initiation of
      rtPA administration via a vein route different from one via which rtPA is injected.

      Thereafter, the subject will be transferred to MRI scanning room to have brain MRI and MRA
      performed, and brain CT will be performed to check the occurrence of intracranial hemorrhage
      at 24 hours after complete administration of the first dose of SP-8203. The subject will be
      closely monitored by research staff daily from the day of first administration of SP-8203
      (Day 0) to Day 5. Brain MRI and MRA will be followed up after the last administration of
      SP-8203 on Day 5. The subject will make a visit on Day 14 to have his/her neurologic symptoms
      checked, after which subject's participation in the trial will be completed.

      *The DSMB (Date Safety Monitoring Board) meeting will be held, to decide whether to proceed
      with Stage 2 or not, based on the results of Stage 1.

      Stage 2- A total of 69 subjects will be enrolled in double-blind, randomized and parallel
      design with 23 subjects assigned to low-dose (40mg/dose, 80mg/ day) SP-8203 group, high-dose
      (80mg/dose, 160mg/day) SP-8203 group or placebo group, respectively.

      If a subject, who is able to be enrolled in Stage 2, has neurological deficit of ≥4 point on
      NIHSS score and give patient's consent to participate in the trial, randomization will be
      performed and each treatment arm (one of three) will be assigned. The subject will receive
      the Investigational products a total of 6 times, with 12 hours intervals. Blood sample will
      be taken after the sixth administration of the Investigational product for pharmacokinetic
      and pharmacodynamics analysis. For pharmacokinetic analysis , blood sample will be taken at
      0, 30, and 120 minutes after the complete sixth administration of the investigational
      products. For pharmacodynamics 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.

      As with Stage 1, the subject will have brain MRI and MRA performed after the administration
      of investigational product, and brain CT will be performed at 24 hours after completion of
      the first administration of investigational products.

      Brain MRI and MRA will be followed-up on Day 5, similarly to Stage 1. However, in Stage 2,
      the subject will make a visit for close monitoring for patient's neurological condition at
      4th week and 12th week. Thereafter, all the procedures of the clinical trial will be
      completed.
    

Intervention name(s): SP-8203 High dose; SP-8203 Low dose; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): High-dose group: 160mg will be intravenously administered as 80mg/dose twice daily (intervals of 12 hours).; Low dose group: 80mg will be intravenously administered as 40mg/dose twice daily (intervals of 12 hours).; Same dosage of SP8203. Placebo will be intravenously administered twice daily (intervals of 12 hours)
Other intervention name(s): SP-8203 is produced by Shin Poong Pharmaceutical company; SP-8203 is produced by Shin Poong Pharmaceutical company
Intervention MeSH terms: Otaplimastat
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: rtPA; Intracranial hemorrhage