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

• ClinicalTrials.gov Identifier: NCT02056574
• Recruitment Status: Withdrawn
• First Posted: February 6, 2014
• Last Update Posted: August 4, 2015
• Sponsor: NoNO Inc.
• Information provided by (Responsible Party): NoNO Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Subarachnoid Hemorrhage; Ruptured Intracranial Aneurysm	Drug: NA-1; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: November 2015
• Estimated Primary Completion Date: November 2019
• Estimated Study Completion Date: April 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Modified Rankin Scale (mRS) [ Time Frame: 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 :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Arizona

Barrow Neurological Institute

Phoenix, Arizona, United States, 850139

United States, Colorado

Colorado Neurological Institute

Englewood, Colorado, United States, 801130000

United States, Michigan

University of Michigan - Neurosurgery

Ann Arbor, Michigan, United States, 481090000

United States, Oregon

Oregon Health and Science University

Portland, Oregon, United States, 97239-3098

United States, Wisconsin

University of Wisconsin

Madison, Wisconsin, United States, 537920000

Canada, Alberta

Foothills Medical Centre

Calgary, Alberta, Canada, T2N 2T9

Canada, Nova Scotia

QEII Health Sciences Centre - Halifax Infirmary

Halifax, Nova Scotia, Canada, B3H 3A7

Canada, Ontario

London Health Sciences Centre

London, Ontario, Canada, N6A 5A5

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada, M4N 3M5

St. Michael's Hospital

Toronto, Ontario, Canada, M5B 1W8

Toronto Western Hospital

Toronto, Ontario, Canada, M5T 2S8

Canada, Quebec

Hopital de l'Enfant Jesus

Quebec City, Quebec, Canada, G1J 1Z4

Sponsors and Collaborators

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

More Information

• Responsible Party: NoNO Inc.
• ClinicalTrials.gov Identifier: NCT02056574
• Other Study ID Numbers: NA-1-006
• First Posted: February 6, 2014
• Last Update Posted: August 4, 2015
• Last Verified: March 2015

Keywords provided by NoNO Inc.:

Endovascular repair; Subarachnoid hemorrhage; Ruptured intracranial aneurysm; Stroke; Coiling; NA-1

Additional relevant MeSH terms:

Subarachnoid Hemorrhage; Intracranial Aneurysm; Aneurysm; Hemorrhage; Rupture; Pathologic Processes; Vascular Diseases; Cardiovascular Diseases; Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Arterial Diseases; Wounds and Injuries