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

Phase 2

Withdrawn

• Conditions: Subarachnoid Hemorrhage; Ruptured Intracranial Aneurysm
• Interventions: Drug: Placebo; Drug: NA-1

• Registration Number: NCT02056574
• Lead Sponsor: NoNO Inc.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-02-04
• Study First Submitted QC: 2014-02-05
• Study First Posted: 2014-02-06
• Status Verified: 2015-03
• Last Update Submitted: 2015-08-03
• Last Update Posted: 2015-08-04
• Study Start: 2015-11
• Primary Completion: 2019-11
• Study Completion: 2020-04

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Single intravenous dose of 2.6 mg/kg of placebo administered as a 10-minute infusion.
NA-1	NA-1	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.

Primary Outcome Measures

Name	Time	Method
Modified Rankin Scale (mRS)	90 days	Proportion of subjects achieving independent functioning as defined as a score of 0-1 on the mRS at Day 90.

Secondary Outcome Measures

Name	Time	Method
Mortality	90 days	Rate of subarachnoid hemorrhage related mortality over the 90 day study period.
National Institutes of Health Stroke Scale (NIHSS)	90 days	Proportion of subjects achieving a good outcome as defined as a score of 0-1 on the NIHSS at Day 90.
Modified Rankin Scale (mRS)	30-45 days	Proportion of subjects achieving a good outcome as defined as a score of 0-1 on the mRS at Day 30-45.
In-hospital length of stay	90 days	Duration of in-hospital length of stay.

Trial Locations

Locations (12)

Foothills Medical Centre; 🇨🇦 Calgary, Alberta, Canada

QEII Health Sciences Centre - Halifax Infirmary; 🇨🇦 Halifax, Nova Scotia, Canada

Barrow Neurological Institute; 🇺🇸 Phoenix, Arizona, United States

Colorado Neurological Institute; 🇺🇸 Englewood, Colorado, United States

Sunnybrook Health Sciences Centre; 🇨🇦 Toronto, Ontario, Canada

University of Michigan - Neurosurgery; 🇺🇸 Ann Arbor, Michigan, United States

Oregon Health and Science University; 🇺🇸 Portland, Oregon, United States

University of Wisconsin; 🇺🇸 Madison, Wisconsin, United States

London Health Sciences Centre; 🇨🇦 London, Ontario, Canada

St. Michael's Hospital; 🇨🇦 Toronto, Ontario, Canada

Toronto Western Hospital; 🇨🇦 Toronto, Ontario, Canada

Hopital de l'Enfant Jesus; 🇨🇦 Quebec City, Quebec, Canada