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

Sponsor

NoNO Inc. (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT02056574

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

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

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 :

Nov 1, 2015

Anticipated Primary Completion Date :

Nov 1, 2019

Anticipated Study Completion Date :

Apr 1, 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

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

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

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.
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.
Mortality [90 days]
Rate of subarachnoid hemorrhage related mortality over the 90 day study period.
In-hospital length of stay [90 days]
Duration of in-hospital length of stay.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.
1. Patient should be Grade II-IV on the WFNS grading scale for SAH.
1. Male or female with a minimum age of 18 years on the day of enrolment.
1. Female subjects of childbearing potential: Negative pregnancy test.
1. 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.
1. Body weight less than or equal to 180 kg.
1. Vital signs on admission:
Blood pressure between 80-180 mm Hg systolic/50-100 mm Hg diastolic;
Body temperature ≤ 38.5C.
1. 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.
1. Dissecting or mycotic brain aneurysm.
1. Planned endovascular vessel sacrifice as the primary modality for aneurysm treatment.
1. Known history of life-threatening allergic reaction to any medication.
1. Chronic renal disease defined as a baseline serum creatinine > 150 µmol/L.
1. Women who are pregnant, or have a positive urine or blood (β-hCG) pregnancy test.
1. Women who are breastfeeding.
1. Any clinically significant psychiatric or psychological disease, which would preclude the patient from completing the protocol.
1. Pre-morbid (estimated) modified Rankin scale score of >1.
1. Previous major stroke.
1. Patients with known HIV infection.
1. Participation in a clinical trial with an investigational drug within 30 days preceding this study.
1. 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.
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 90 days.

Contacts and Locations

Locations

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