E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Ischemic Stroke
Stroke is the most common neurologic disorder and is the third leading cause of death in developed countries, after myocardial infarction and cancer. Stroke is the second leading cause of neurological morbidity in the United States, Europe, and Japan. 67%- 81% of all stroke cases are ischemic strokes. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10055221 |
E.1.2 | Term | Ischemic stroke |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to compare the clinical therapeutic effects of intravenous DP-b99 at a dose of 1.0 mg/kg initiated within nine hours of stroke onset and administered daily over 2 hours for 4 consecutive days versus placebo in subjects with moderately severe, likely hemispheric, acute ischemic stroke. The clinical outcome will be measured by the modified Rankin Scale at day 90. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to compare the safety and tolerability, as well as post-stroke recovery at Day 90, in subjects treated with DP-b99 versus placebo. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or females 18 to 85 years of age, inclusive
2. Have suffered an acute, likely hemispheric, ischemic stroke, defined as acute, focal, neurological deficit(s), secondary to a presumed vascular event, which must include at least one of the following components (as reflected by at least 1 point on any of the corresponding items of the NIHSS: 3, 9 or 11): - Visual - Best Language - Extinction and Inattention (formerly Neglect)
3. Have suffered the onset of an acute ischemic stroke that can be evaluated and treatment initiated within 9 hours after the onset of acute ischemic stroke symptoms. (Onset is defined as the time that the subject was last seen in a normal state, or bedtime for unwitnessed strokes occurring during sleep.)
4. Have at screening a NIHSS score of 10 to 16, inclusive
5. Have readily accessible peripheral venous access for clinical trial material (CTM) administration and blood sampling
6. Have the ability to understand the requirements of the study and be willing to provide written informed consent (IC) (as evidenced by signature on an informed consent document approved by an independent ethics committee (IEC), and agree to abide by the study restrictions and return for the required assessments. (In the event of incapacitated subjects, informed consent will be sought from a legally acceptable representative or by any other means as approved by the IRB or IEC). |
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E.4 | Principal exclusion criteria |
1. Have an intracerebral or subarachnoid hemorrhage per screening/baseline computerized tomography (CT) scan or susceptibility-weighted magnetic resonance imaging (MRI)
2. Be a candidate for either: a. thrombolytic therapy or have been treated with thrombolytic therapy for the current stroke b. mechanical thromboembolectemy, or have been treated with mechanical thromboembolectemy for the current stroke
3. Be delirious, comatose or stuporous (a score of ≥2 on item 1.a of the NIHSS) or demented, or having a mental impairment that in the investigator’s opinion renders the subject incapable to participate in the study
4. Have seizure(s) anytime from stroke onset to screening/baseline NIHSS evaluation
5. Have neurological or non-neurological comorbidities that in the investigator’s opinion may lead, independent of the current stroke, to further deterioration in the subject’s neurological status during the trial period, or may render the study’s neurological assessments inconclusive for the purpose of evaluating solely the stroke’s effects (e.g., metabolic encephalopathies, hemiplegic migraine, multiple sclerosis, central nervous system tumor, convulsive disorder, monocular blindness)
6. Be likely to undergo a procedure involving cardiopulmonary bypass during the study period
7. Have suffered a myocardial infarction in the last 90 days
8. Have any medical condition that in the investigator’s opinion may threaten the subject’s ability to complete the study (e.g., concurrent significant or life-threatening diseases, such as malignancies or end stage organ failure)
9. Have rapid spontaneous improvement of neurological signs during screening/baseline assessments
10. Have premorbid neurological deficits and functional limitations assessed by a pre-stroke Modified Rankin Scale score of > 1
11. Have suffered a stroke within 90 days of the screening/baseline assessments that is either diagnostically confirmed or assumed to be in the same cerebral territory as is the current acute stroke
12. Have either severe hypertension (systolic blood pressure (BP) >220 mm Hg or diastolic BP >120 mm Hg) or hypotension (systolic BP <90 mm Hg), as measured by at least 2 consecutive supine measurements taken 10 minutes apart prior to randomization
13. Have significant current renal or hepatic disease(s): a serum creatinine concentration of >2.5 mg/dL; alanine aminotransferase (ALT), aspartate aminotransferase (AST), or gamma-glutamyl transferase (GGT) values that are three times greater the upper limit of normal (ULN) (or, if GGTcannot be evaluated, direct bilirubin must not be greater than 1.5 times the ULN)
14. Have a platelet count of <100,000/mm3 or for patients on oral anticoagulants at study entry, INR of >4
15. Be a female of childbearing potential (less than 2 years’ postmenopausal or not surgically sterilized) who is not willing to use adequate and effective birth control measures for the duration of the trial. Effective birth control measures include hormonal contraception, a barrier method such as a diaphragm, intrauterine device (IUD) and/or condom with spermicide (IUD, diaphragm, condoms alone or the rhythm method are not considered reliable methods)
16. Have a positive urine pregnancy test at screening/baseline or be a lactating female
17. Be currently dependent on, or abusing, alcohol or one or more of the following: sympathomimetic amines (amphetamine-like), cannabis, cocaine, hallucinogens, inhalants, opioids, phencyclidine, sedatives and hypnotics
18. Have received an investigational drug or product or participated in an investigational drug study within a period of 30 days prior to receiving study medication or have previously participated in a clinical trial involving DP-b99
19. Have severe anemia as measured by a hemoglobin vanlue of <7 g/dl
20. Being in a dependant relationship with the physician or study sponsor
21. Known hypersensitivity to any component of the investigational product |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the mRS score at 90 days (or on last rating) following stroke onset as analyzed across the whole distribution of scores (“shift analysis”). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of the trial will be when a total of 770 subjects have been randomized. Since this study is monitored by a data safety monitoring board (DSMB), this board may stop the trial early for the following reasons: A. Exposure to DP-b99 proves to be unsafe after weighing the pre-determined safety factors as detailed in the DSMB charter or B. The futility analysis reached its pre-specified futility threshold |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |