Evaluating Neuroprotection in Aneurysm Coiling Therapy "ENACT"


Phase 2 Results

Eligibility Criteria

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.