Ischemic StrokePhase 2SP-8203-2002NCT04479449
Efficacy and Safety of SP-8203 in Patients With Ischemic Stroke Requiring rtPA
A Phase 2 study testing SP-8203 in people with Ischemic Stroke, run by Shin Poong Pharmaceutical Co. Ltd. at 1 site in South Korea.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 19 to 85 years
- Conditions the study is for
- Ischemic Stroke
- What is being tested?
- SP-8203
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 178 participants
- Where
- 1 siteSouth Korea
- Study dates
- 18 Mar 2019to 18 Dec 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 19Show fewer
- 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 locations and contacts
1 site in 1 country.
About this study
Official title: A Prospective, Randomized, Double-blind Phase 2b Clinical Trial to Investigate the Efficacy and Safety of SP-8203 in Patients With Acute Ischemic Stroke Requiring Recombinant Tissue Plasminogen Activator (rtPA) Standard of Care
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.
Read the detailed 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).
- Conditions
- Ischemic Stroke
- Being tested
- SP-8203, Placebo
- Keywords
- SP-8203 (Otaplimastat), rtPA (recombinant tissue Plasminogen Activator)
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SP-8203Drug
Also called Otaplimastat (SP-8203)
SP-8203 80 mg will be intravenously administered as 40 mg/dose twice daily (intervals of 12 hours)
PlaceboDrug
Placebo will be intravenously administered twice daily (intervals of 12 hours)
| Study group | Role | What they receive |
|---|---|---|
| SP-8203 | Experimental | SP-8203 80 mg (40 mg/dose twice a day for three days) Receives: Drug: SP-8203 |
| Placebo | Placebo comparator | Placebo group: twice a day for three days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The neurological improvement evaluated by the National Institute of Health Stroke Scale (NIHSS)
The neurological improvement evaluated by the National Institute of Health Stroke Scale (NIHSS) until 28 day in subjects with acute ischemic stroke requiring rtPA (recombinant tissue Plasminogen Activator) 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.
Measured: Change from 0 day at 28 days
Secondary outcomes (11)
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 rtPA standard of care
Measured: Day 1
The difference in the distribution of modified Rankin Scale (mRS) scores
The difference in the distribution of modified Rankin Scale (mRS) scores in subjects with acute ischemic stroke requiring rtPA standard of care. The 0-6 point-scales are scored according to symptoms with 0 point indicating no disability; the higher score denotes ofr the more severe degree of disability.
Measured: Day 90
The change in the 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.
Measured: Change from 0 day at 90 days
The change in Barthel index
The change in Barthel index in subjects with acute ischemic stroke requiring rtPA standard of care
Measured: Change from 0 day at 90 days
The fold change of infarct growth classified by modified Treatment in Cerebral Ischemia (mTICI) grade within 5 days
MRI (DWI) imaging outcomes
Measured: Day 5
The number of occurrence and volume of intracranial hemorrhage classified by mTICI grade within 5 days
MRI (GRE) imaging outcomes
Measured: Day 5
The incidence of serious adverse events
The incidence of serious adverse events
Measured: follow-up to 30 days after the last visit
The rate of death
The rate of death due to any cause
Measured: follow-up to 30 days after the last visit
The incidence rate of adverse events, and adverse drug reaction
The incidence rate of adverse events, and adverse drug reaction
Measured: follow-up to 30 days after the last visit
The incidence of symptomatic Intracranial Hemorrhage (sICH)
The incidence of sICH occurring within 5 days of administration according to the definition described on the protocol
Measured: within 5 days of administration
The Incidence of major systemic bleeding
The Incidence of major systemic bleeding according to the International Society of Thrombosis and Hemostasis (ISTH) definition
Measured: within 5 days of administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2020
- Study start18 Mar 2019
- Primary completion19 Oct 2020
- Study completion18 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ischemic StrokeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 178 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shin Poong Pharmaceutical Co. Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jong Sung Kim, MD, Phd, Study chair, Asan Medical CenterDae-IL Chang, MD, Phd, Principal investigator, Kyunghee University Medical CenterKyung Mi Oh, MD, Phd, Principal investigator, Korea University Guro HospitalJong-Ho Park, MD, Phd, Principal investigator, Myongji HospitalKyung Bok Lee, MD, Phd, Principal investigator, Soonchunhyang University HospitalSang Min Sung, MD, Phd, Principal investigator, Pusan National University HospitalEung-Gyu Kim, MD, Phd, Principal investigator, Inje UniversityHee-Joon Bae, MD, Phd, Principal investigator, Seoul National University Bundang Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04479449
- Sponsor's protocol ID
- SP-8203-2002
- Acronym
- SP-8203-2002
- Status last verified
- Mar 2023
- First submitted
- 14 Jul 2020
- Last updated
- 8 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Randomized, Double-blind Phase 2b Clinical Trial to Investigate the Efficacy and Safety of SP-8203 in Patients With Acute Ischemic Stroke Requiring Recombinant Tissue Plasminogen Activator (rtPA) Standard of Care
- ClinicalTrials.gov ID
- NCT04479449
- Acronym / sponsor ID
- SP-8203-2002 / SP-8203-2002
- Conditions
- Ischemic Stroke
- Keywords
- SP-8203 (Otaplimastat), rtPA (recombinant tissue Plasminogen Activator)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 178 participants (actual)
- Lead sponsor
- Shin Poong Pharmaceutical Co. Ltd.Industry (pharma, biotech, devices)
- Study start
- 18 Mar 2019 (actual)
- Primary completion
- 19 Oct 2020 (actual)
- Study completion
- 18 Dec 2020 (actual)
- First posted
- 21 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SP-8203 | Experimental | Drug: SP-8203SP-8203 80 mg (40 mg/dose twice a day for three days) |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo group: twice a day for three days |
Who may qualify
- Ages
- 19 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (19 listed)
- 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:
- Patients with severe heart failure of New York Heart Association (NYHA) Class III or Class IV.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SP-8203Also: Otaplimastat (SP-8203)SP-8203 80 mg will be intravenously administered as 40 mg/dose twice daily (intervals of 12 hours) | Drug | SP-8203 |
| PlaceboPlacebo will be intravenously administered twice daily (intervals of 12 hours) | Drug | Placebo |
Primary outcome
The neurological improvement evaluated by the National Institute of Health Stroke Scale (NIHSS)
Time frame: Change from 0 day at 28 days
The neurological improvement evaluated by the National Institute of Health Stroke Scale (NIHSS) until 28 day in subjects with acute ischemic stroke requiring rtPA (recombinant tissue Plasminogen Activator) 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.
11 secondary outcomes
Incidence of parenchymal hematoma observed on brain Computed Tomography (CT) scan
Time frame: Day 1
The difference in the distribution of modified Rankin Scale (mRS) scores
Time frame: Day 90
The change in the National Institute of Health Stroke Scale (NIHSS) scores
Time frame: Change from 0 day at 90 days
The change in Barthel index
Time frame: Change from 0 day at 90 days
The fold change of infarct growth classified by modified Treatment in Cerebral Ischemia (mTICI) grade within 5 days
Time frame: Day 5
The number of occurrence and volume of intracranial hemorrhage classified by mTICI grade within 5 days
Time frame: Day 5
The incidence of serious adverse events
Time frame: follow-up to 30 days after the last visit
The rate of death
Time frame: follow-up to 30 days after the last visit
The incidence rate of adverse events, and adverse drug reaction
Time frame: follow-up to 30 days after the last visit
The incidence of symptomatic Intracranial Hemorrhage (sICH)
Time frame: within 5 days of administration
The Incidence of major systemic bleeding
Time frame: within 5 days of administration
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2023.
Related trials for Ischemic Stroke
Not yet recruiting
Temporal Interference Stimulation for Upper-Limb Motor Recovery in Early Subacute Stroke
Acute Ischemic Stroke
RecruitingObservational study
ELATE Study: Evaluating Large-vessel Acute Thrombectomy in Extended Time Window
Acute Ichemic Stroke
Not yet recruiting
Selective Intra-Arterial Hypothermia After Endovascular Treatment for Acute Basilar Artery Occlusion
Acute Ischemic Stroke, Basilar Artery Occlusion
Active, not recruiting
Improving Visual Field Deficits With Noninvasive Brain Stimulation
Visual Field Defect, Peripheral, Stroke
Recruiting
Biomarkers of Paired VNS
Stroke, Ischemic
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jong Sung Kim, MD, Phd study chair
Asan Medical Center
Dae-IL Chang, MD, Phd principal investigator
Kyunghee University Medical Center
Kyung Mi Oh, MD, Phd principal investigator
Korea University Guro Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SP-8203 in people with Ischemic Stroke, run by Shin Poong Pharmaceutical Co. Ltd. at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The neurological improvement evaluated by the National Institute of Health Stroke Scale (NIHSS) (time frame: Change from 0 day at 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2023.