Evaluating Neuroprotection in Aneurysm Coiling Therapy

Inclusion Criteria

   - A diagnosis of a ruptured or unruptured brain aneurysm deemed suitable for repair by
   neuroendovascular techniques involving intraluminal occlusion by detachable platinum
   coils, stent-assisted coiling, pipeline stent, balloon-assisted coiling, covered stent
   only, neck-bridge device, re-coiling, or re-treatment of a previously coiled/treated
   aneurysm. There are no restrictions on adjunctive devices. For patients with a
   ruptured aneurysm, endovascular repair must take place within 72 hours of the ictal
   haemorrhage.

   - If the aneurysm has ruptured, patient should be Grade I-III on the World Federation of
   Neurological Surgeons (WFNS) grading scale for subarachnoid hemorrhage. If the patient
   is intubated but alert and able to follow commands (at least a 2-step command), and is
   not kept intubated for neurological status (i.e., WFNS Grade IV or V), the patient is
   considered WFNS Grade III and is eligible for the trial.

   - Absence of ongoing ischemic symptoms such as transient ischemic attacks, minor
   strokes, stroke-in-evolution, or clinical evidence of cerebral vasospasm within 2
   weeks prior to randomization. (If a CT scan, cerebral angiogram, or other imaging
   performed during the 2 weeks prior to randomization shows radiological vasospasm
   deemed by the treating physician to be potentially clinically significant, the subject
   is excluded.)

   - Brain MRI imaging (DWI and FLAIR sequences) within 2 weeks prior to the endovascular
   aneurysm repair procedure as detailed in Section 8.2. Imaging must not demonstrate any
   focal ischemic stroke defined as a new region of restricted diffusion and/or a focal
   area of reduced perfusion on a relative mean transit time (rMTT) or relative time to
   peak (rTTP) map

   - Male or female with a minimum age of 18 years on the day of enrolment.

   - Female subjects of childbearing potential: Negative pregnancy test. After enrolment,
   blood will be drawn from women of childbearing potential for a confirmatory test of
   pregnancy as evaluated by a serum B-hCG test. The definition of non-childbearing
   potential includes the following:

      - Surgically sterile (e.g., hysterectomy with or without oophorectomy; fallopian
      tube ligation; endometrial ablation), at least 30 days prior to signature of the
      Informed Consent form

      - At least 5 years post-menopause (i.e., 6 years post last menstrual period), or
      menopause confirmed by follicle-stimulating hormone (FSH) testing. Non-surgically
      sterile females or females with undocumented post-menopausal status must be
      willing to use a medically approved method of birth control for 3 months after
      completion of dosing.

   - 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.

   - Body weight less than or equal to 180 kg.

   - Normal or abnormal but not clinically significant findings in the

      - non-neurological physical examination

      - 12-lead ECG

      - PQ or PR interval less than or equal to 210 msec;

      - In unruptured aneurysm cases, QTc interval less than 450 msec for males or 470
      msec for females. For ruptured aneurysm cases, QTc interval is not restricted.

      - vital signs

      - blood pressure between 80-180/50-100 mm Hg,

      - body temperature less than or equal to 38.5oC

   - Informed consent and availability of the subject for the entire study period and
   willingness of the subject to adhere to protocol requirements, as evidenced by a
   signed Informed Consent Form.

Exclusion Criteria

   - Dissecting or mycotic brain aneurysm. Fusiform or atherosclerotic intracerebral
   aneurysms may be eligible for the trial if endovascular treatment is planned with a
   goal of exclusion of the aneurysm from the circulation.

   - Planned endovascular vessel sacrifice as the primary modality for aneurysm treatment.

   - Known history of life-threatening allergic reaction to any medication.

   - Chronic renal disease defined as a baseline serum creatinine > 150 umol/L.

   - Women who are pregnant, or have a positive urine or blood (β-hCG) pregnancy test.

   - Women who are breastfeeding.

   - Any clinically significant psychiatric or psychological disease, which would preclude
   the patient from completing the protocol.

   - Pre-morbid (estimated) modified Rankin scale score of greater than 2.

   - Previous serious traumatic brain injury that would preclude the patient from
   completing the protocol or preclude MRI analysis of small strokes.

   - Patients with known HIV infection.

   - Patients who are unable to have an MRI scan for any reason.

   - Participation in a clinical trial with an investigational drug within 30 days
   preceding this study. 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.

   - 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 30 days.