E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
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 main objective of this study is to provide information regarding the safety, tolerability, and activity in promoting recanalization (at 90 minutes) of escalating doses of MRX-801 accompanied by continuous ultrasound (US) in conjunction with intravenous tPA in subjects with acute ischemic stroke. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of this study is to provide preliminary data on longer term outcomes for subjects receiving treatment with MRX-801/US/tPA in comparison with controls receiving current standard of care treatment with tPA alone. Rates of clinical recovery will be determined at 2 hours, 24-36 hours, and 3 months post-treatment using accepted measures of neurological status and overall disability and handicap (National Institutes of Health Stroke Scale (NIHSS) score and modified Rankin scale (mRS) scores, respectively). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the trial: 1. Males or females 18 years of age or older.
2. Patients with a diagnosis of intracranial arterial occlusion of the middle cerebral artery (MCA), anterior cerebral artery (ACA), internal carotid artery (ICA), posterior cerebral artery (PCA), or distal basilar artery as demonstrated by US.
3. Patients with neurological deficit measurable by NIHSS score, and that in the opinion of the treating physician requires treatment with full dose IV tPA.
4. Patients with persisting arterial occlusion and without frank resolution of neurological symptoms at the time of diagnostic ultrasound imaging, who, in accordance with local and federal guidelines for use, are eligible for intravenous tPA or have been receiving intravenous tPA for up to 45 minutes
5. Provision of informed consent as demonstrated by the patient’s signature or by the signature of the patient’s authorized legal representative on the Informed Consent Form in accordance with all local and federal regulations.
6. Co-signature on the Informed Consent Form by a qualified member of the study staff signifying that, in his/her professional opinion, informed consent has been obtained in accordance with all local and federal regulations.
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E.4 | Principal exclusion criteria |
Patients presenting with any of the following will not be included in the trial:
1. Evidence of hemorrhage on non-contrast head CT or MRI scan;
2. Patients with primary intra-arterial thrombolysis.
3. Patients with known right-to-left cardiac shunts as determined from medical history or patient chart.
4. Patients with any known hypersensitivity to the test article or any other diagnostic agents or therapeutics to be used.
5. Patients without temporal insonation windows.
6. Female and pregnant or breast feeding.
7. Patients receiving other investigational drugs, procedures, or therapies within 30 days prior to study treatment.
8. Patients with any standard contraindication for intravenous tPA therapy.
9. Patients with moderate to severe COPD (baseline O2 saturation less than 80% on room air);
10. Significant concurrent medical/neurological conditions or deviation from normal laboratory test values at baseline that, in the opinion of the investigator, pose significant risk to the patient and warrant exclusion from the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary safety endpoint is a comparison of MRX-801/US and tPA with standard of care tPA treatment (control group) for proportions of subjects experiencing symptomatic intracranial hemorrhage (sICH) within 36 hours of treatment.
The primary activity endpoint will be assessed from 0 to 120 minutes from initiation of study treatment as follows: • Proportion of subjects achieving partial or complete recanalization at 120 minutes; • Proportion of subjects achieving any partial or complete recanalization within 120 minutes from initiation of treatment; • Time to complete recanalization. |
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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 | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Yes |
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 | Yes |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Dose escalation, blinded endpoint assessment |
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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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
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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Please refer to the Protocol |
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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 | |
E.8.9.1 | In the Member State concerned months | 13 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 15 |