Safety and Efficacy Study of a Single Dose of NA-1 in Patients Undergoing Endovascular Repair of Ruptured Aneurysms (ENACT-2)

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Subarachnoid Hemorrhage; Ruptured Intracranial Aneurysm
• Intervention / Treatment: Drug: Placebo; Drug: NA-1

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Foothills Medical Centre
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 3A7
      • QEII Health Sciences Centre - Halifax Infirmary
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
    • Toronto, Ontario, Canada, M5T 2S8
      • Toronto Western Hospital
  • Quebec
    • Quebec City, Quebec, Canada, G1J 1Z4
      • Hopital de l'Enfant Jesus
• United States
  • Arizona
    • Phoenix, Arizona, United States, 850139
      • Barrow Neurological Institute
  • Colorado
    • Englewood, Colorado, United States, 801130000
      • Colorado Neurological Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 481090000
      • University of Michigan - Neurosurgery
  • Oregon
    • Portland, Oregon, United States, 97239-3098
      • Oregon Health and Science University
  • Wisconsin
    • Madison, Wisconsin, United States, 537920000
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: NoNO Inc.
• Investigators: Study Director: Michael Tymianski, MD, PhD, NoNO Inc.; Principal Investigator: Cameron G McDougall, MD, Barrow Neurological Institute; Principal Investigator: Michael D Hill, MD, Foothills Medical Centre

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Anticipated): November 1, 2019
• Study Completion (Anticipated): April 1, 2020

Study Registration Dates

• First Submitted: February 4, 2014
• First Submitted That Met QC Criteria: February 5, 2014
• First Posted (Estimate): February 6, 2014

Study Record Updates

• Last Update Posted (Estimate): August 4, 2015
• Last Update Submitted That Met QC Criteria: August 3, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Stroke; Endovascular repair; Subarachnoid hemorrhage; Coiling; NA-1; Ruptured intracranial aneurysm
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Arterial Diseases; Intracranial Hemorrhages; Hemorrhage; Aneurysm; Subarachnoid Hemorrhage; Intracranial Aneurysm
• Other Study ID Numbers: NA-1-006