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This is a randomized, double-blind, placebo-controlled, single-dose study investigating the safety and efficacy of NA-1 in patients with subarachnoid hemorrhage (SAH) undergoing endovascular repair of ruptured intracranial aneurysms. Up to 300 male and female patients with SAH undergoing endovascular repair of a ruptured intracranial aneurysm will be dosed with 2.60 mg/kg of NA-1 or placebo as a 10 minute intravenous infusion after completion of the endovascular procedure on Day 1 of the study period. Subjects will undergo interim procedures at Day 2-4, Day 30-45, and end-of-study procedures on Day 90.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NA-1 | Experimental | 20 amino acid peptide that consists of a 9 amino acid domain that inhibits PSD-95 and an 11 amino acid domain that enables the peptide to cross the blood-brain barrier. Single intravenous dose of 2.6 mg/kg of NA-1 administered as a 10-minute infusion. |
|
| Placebo | Placebo Comparator | Single intravenous dose of 2.6 mg/kg of placebo administered as a 10-minute infusion. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| NA-1 | Drug |
| ||
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Modified Rankin Scale (mRS) | Proportion of subjects achieving independent functioning as defined as a score of 0-1 on the mRS at Day 90. | 90 days |
| Measure | Description | Time Frame |
|---|---|---|
| Modified Rankin Scale (mRS) | Proportion of subjects achieving a good outcome as defined as a score of 0-1 on the mRS at Day 30-45. | 30-45 days |
| National Institutes of Health Stroke Scale (NIHSS) |
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Inclusion Criteria:
1. A diagnosis of a ruptured brain aneurysm deemed suitable for repair by neuroendovascular techniques involving intraluminal occlusion by detachable platinum coils, or any neuroendovascular technique such as balloon-assisted coiling, stenting, or flowed diversion.
2. Patient should be Grade II-IV on the WFNS grading scale for SAH.
3. Male or female with a minimum age of 18 years on the day of enrolment.
4. Female subjects of childbearing potential: Negative pregnancy test.
5. Non-surgically sterile males or males with partners of childbearing potential must be willing to use condoms with spermicide for 3 months after completion of dosing.
6. Body weight less than or equal to 180 kg.
7. Vital signs on admission:
8. Informed consent and availability of the subject for the entire study period and willingness of the subject to adhere to protocol requirements.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael Tymianski, MD, PhD | NoNO Inc. | Study Director |
| Cameron G McDougall, MD | Barrow Neurological Institute | Principal Investigator |
| Michael D Hill, MD | Foothills Medical Centre | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Barrow Neurological Institute | Phoenix | Arizona | 850139 | United States | ||
| Colorado Neurological Institute |
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|
Proportion of subjects achieving a good outcome as defined as a score of 0-1 on the NIHSS at Day 90.
| 90 days |
| Mortality | Rate of subarachnoid hemorrhage related mortality over the 90 day study period. | 90 days |
| In-hospital length of stay | Duration of in-hospital length of stay. | 90 days |
| Englewood |
| Colorado |
| 801130000 |
| United States |
| University of Michigan - Neurosurgery | Ann Arbor | Michigan | 481090000 | United States |
| Oregon Health and Science University | Portland | Oregon | 97239-3098 | United States |
| University of Wisconsin | Madison | Wisconsin | 537920000 | United States |
| Foothills Medical Centre | Calgary | Alberta | T2N 2T9 | Canada |
| QEII Health Sciences Centre - Halifax Infirmary | Halifax | Nova Scotia | B3H 3A7 | Canada |
| London Health Sciences Centre | London | Ontario | N6A 5A5 | Canada |
| Sunnybrook Health Sciences Centre | Toronto | Ontario | M4N 3M5 | Canada |
| St. Michael's Hospital | Toronto | Ontario | M5B 1W8 | Canada |
| Toronto Western Hospital | Toronto | Ontario | M5T 2S8 | Canada |
| Hopital de l'Enfant Jesus | Québec | Quebec | G1J 1Z4 | Canada |
| ID | Term |
|---|---|
| D013345 | Subarachnoid Hemorrhage |
| D020521 | Stroke |
| ID | Term |
|---|---|
| D020300 | Intracranial Hemorrhages |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D006470 | Hemorrhage |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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