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Efficacy and Safety of SP-8203 in Patients With Ischemic Stroke Requiring rtPA (SP-8203-2002)

S

Shin Poong Pharmaceutical

Status and phase

Completed
Phase 2

Conditions

Ischemic Stroke

Treatments

Drug: Placebo
Drug: SP-8203

Study type

Interventional

Funder types

Industry

Identifiers

NCT04479449
SP-8203-2002

Details and patient eligibility

About

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.

Full description

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).

Enrollment

178 patients

Sex

All

Ages

19 to 85 years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Triple Blind

178 participants in 2 patient groups, including a placebo group

SP-8203
Experimental group
Description:
SP-8203 80 mg (40 mg/dose twice a day for three days)
Treatment:
Drug: SP-8203
Placebo
Placebo Comparator group
Description:
Placebo group: twice a day for three days
Treatment:
Drug: Placebo

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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