Safety and Efficacy Study of a Single Dose of NA-1 in Patients Undergoing Endovascular Repair of Ruptured Aneurysms

Study Overview
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Brief Summary
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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.

Official Title
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Phase 2, Multicenter Randomized, Double-Blind, Placebo-Controlled, Safety and Efficacy Study Evaluating a Single Dose of Intravenous NA-1 in Patients With Subarachnoid Hemorrhage Undergoing Endovascular Repair of Ruptured Intracranial Aneurysms

Conditions
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Subarachnoid Hemorrhage, Ruptured Intracranial Aneurysm

Intervention / Treatment
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* Drug: NA-1
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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: Blood pressure between 80-180 mm Hg systolic/50-100 mm Hg diastolic; Body temperature ≤ 38.5C. 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: 1. Prior SAH within 6 months of presentation. 2. Dissecting or mycotic brain aneurysm. 3. Planned endovascular vessel sacrifice as the primary modality for aneurysm treatment. 4. Known history of life-threatening allergic reaction to any medication. 5. Chronic renal disease defined as a baseline serum creatinine > 150 µmol/L. 6. Women who are pregnant, or have a positive urine or blood (β-hCG) pregnancy test. 7. Women who are breastfeeding. 8. Any clinically significant psychiatric or psychological disease, which would preclude the patient from completing the protocol. 9. Pre-morbid (estimated) modified Rankin scale score of >1. 10. Previous major stroke. 11. Patients with known HIV infection. 12. Participation in a clinical trial with an investigational drug within 30 days preceding this study. 13. Previous participation in the ENACT trial (e.g, to treat a prior aneurysm), participation in another trial involving NA-1 or prior receipt of NA-1. 14. Any other medical condition that the site investigator deems would put the patient at excessive risk of participation in the study or an expected life expectancy less than 1 year or that would result in inability to collect clinical outcomes at 90 days.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NA-1<br>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. | Drug: NA-1<br> <br> |
| Placebo Comparator: Placebo<br>Single intravenous dose of 2.6 mg/kg of placebo administered as a 10-minute infusion. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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) | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Subarachnoid hemorrhage, Ruptured intracranial aneurysm, Stroke, Coiling, NA-1, Endovascular repair