E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10055221 |
E.1.2 | Term | Ischemic stroke |
E.1.2 | System Organ Class | 100000004852 |
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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 the study is to assess the effects of natalizumab versus placebo in acute ischemic stroke on clinical measures of independence and activities of daily life |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of the study is to explore dose and exposure response and the clinical treatment effects of natalizumab versus placebo in acute ischemic stroke on the following measures of independence, activities of daily living, neurologic function, quality of life, and cognition and safety and tolerability. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Clinical diagnosis of supratentorial acute ischemic stroke defined by
LKN ≤24 hours prior to study treatment initiation.
- Score of 5 to 23 points, inclusive, on the NIHSS at Screening for
subjects initiating treatment ≤9 hours from LKN. Note: NIHSS eligibility
must be confirmed within 60 minutes prior to randomization.
- Score of 5 to 15 points, inclusive, on the NIHSS at Screening for
subjects initiating treatment >9 to ≤24 hours from LKN. Note: NIHSS
eligibility must be confirmed within 60 minutes prior to randomization.
- Prior to index stroke, patient was able to perform basic activities of
daily living without assistance: dressing, eating, walking, bathing, and
using the toilet.
- For those subjects who underwent a cranial MRI, there is at least 1
acute infarct with a diameter of ≥2 cm on baseline brain diffusionweighted
imaging.
NOTE: Other protocol-defined inclusion criteria may apply. |
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E.4 | Principal exclusion criteria |
- Lacunar or isolated brainstem or cerebellar stroke based on clinical assessment and available acute imaging studies performed under the
standard of care.
- Presence of acute intracranial hemorrhage on acute brain CT or MRI.
However, petechial hemorrhages of ≤1 cm are not exclusionary.
- Severe stroke.
- Seizure at the onset of stroke.
- Known history of prior treatment with natalizumab.
- Known history of active viral hepatitis B or C.
- Signs and symptoms of active or acute infection.
NOTE: Other protocol-defined exclusion criteria may apply.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is a composite global measure of functional disability based on a score of 0 or 1 on the mRS and a score of ≥95 on the BI at Day 90 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The secondary endpoints are:
- mRS score at Day 90
- BI score at Day 90
- SIS-16 score at Day 90
- MoCA score at Day 90
- Safety (incidence and proportion of AEs and SAEs)
- NIHSS score at Day 90 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- mRS score: Day 90
- BI score: Day 90
- SIS-16 score: Day 90
- MoCA score: Day 90
- AEs and SAEs: throughout the study, as necessary
- NIHSS score at Day 90
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 21 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 | No |
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 |
Germany |
Spain |
United Kingdom |
United States |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |