StrokePhase 2ENACTNCT00728182
Evaluating Neuroprotection in Aneurysm Coiling Therapy
A Phase 2 study testing NA-1 in people with Stroke, run by NoNO Inc. at 14 sites in 2 countries.
Trial summary
This is a randomized, double-blind, placebo-controlled, single-dose, design investigating the safety, tolerability and efficacy of NA-1, a peptide designed to reduce ischemic brain damage. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stroke
- What is being tested?
- NA-1
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 185 participants
- Where
- 14 sitesin 2 countries
- Study dates
- Aug 2008to May 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
14 sites in 2 countries.
14 sites in 2 countries
Canada11 sites
Foothills Medical Centre
Calgary, Alberta, T2N 2T9
University of Alberta Hospital
Edmonton, Alberta, T6G 2B7
QEII Health Sciences Centre - Halifax Infirmary
Halifax, Nova Scotia, B3H 3A7
Hamilton Health Sciences General Site
Hamilton, Ontario, L8X 2S2
London Health Sciences Centre
London, Ontario, N6A 5A5
Hôpital Notre-Dame du Centre Hospitalier de l'Université de Montréal (CHUM)
Montreal, Quebec, H2L 4M1
The Ottawa Hospital - Civic Campus
Ottawa, Ontario, K1Y 4E9
Hopital de l'Enfant Jesus
Québec, Quebec, G1J 1Z4
Royal University Hospital
Saskatoon, Saskatchewan, S7N0W8
St. Michael's Hospital
Toronto, Ontario, M5B 2W8
Toronto Western Hospital
Toronto, Ontario, M5T 2S8
United States3 sites
Barrow Neurological Institute
Phoenix, Arizona, 85013
Oregon Health and Science University
Portland, Oregon, 97239
Stanford University Medical Center
Stanford, California, 94305
About this study
Official title: A Phase II, Multicenter, Randomized, Fasting, Double-Blind, Placebo-Controlled, Safety, Tolerability and Efficacy Study Evaluating a Single Dose of Intravenous NA-1 in Male and Female Patients Undergoing Endovascular Repair of Brain Aneurysms
This is a randomized, double-blind, placebo-controlled, single-dose, design investigating the safety, tolerability and efficacy of NA-1, a peptide designed to reduce ischemic brain damage. Up to 200 male and female patients undergoing endovascular repair of brain 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 Days 2-4 and end-of study procedures on Day 30. Standard safety criteria will be analysed. Efficacy endpoints include the ability of NA-1 to: 1) reduce the volume of ischemic embolic strokes, 2) reduce the number of ischemic embolic strokes, 3) reduce vascular cognitive impairment, and 4) reduce the frequency of large strokes induced by the endovascular procedure. The plasma concentrations of NA-1 will also be analyzed.
- Conditions
- Stroke
- Being tested
- NA-1, Placebo
- Keywords
- Stroke, Vascular cognitive impairment, Coiling, Endovascular repair, Brain aneurysm, NA-1
- Medical subject headings
- Stroke, Intracranial Aneurysm
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NA-1Drug
single intravenous dose of 2.6 mg/kg of NA-1 administered as a 10-minute infusion
PlaceboDrug
single intravenous dose of 2.6 mg/kg of placebo administered as a 10-minute infusion
| Study group | Role | What they receive |
|---|---|---|
| NA-1 | Experimental | 20 amino acid peptide that consists of a 9 amino acid domain that inhibits PSD-95 and a 11 amino acid domain than enables the peptide to cross the blood-brain barrier. Receives: Drug: NA-1 |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Volume of New FLAIR Lesions(MRI)
Volume of new ischemic lesions as defined by FLAIR MRI at 12-95 hours postdose
Measured: Enrolment, Days 2-4
Secondary outcomes (5)
Number of New DWI Lesions (MRI)
Number of new ischemic lesions as defined by DWI MRI at 12-95 hours postdose.
Measured: Enrolment, Day 2-4
Number of New FLAIR Lesions (MRI)
Number of new ischemic lesions as defined by FLAIR MRI at 12-95 hours postdose.
Measured: Enrolment, Days 2-4
Volume of New DWI Lesions (MRI)
Volume of new DWI lesions as defined by MRI at 12-95 hours postdose.
Measured: Enrolment, Days 2-4
National Institutes of Health Stroke Scale (NIHSS).
The NIHSS is a standardized neurological method to measure disability and recovery after stroke. Scores range from 0 to 42, with higher scores indicating increasing severity. Scores were dichotomized into 0-1 (good outcome) versus 2 or above. The number of participants scoring 0-1 on the NIHSS at Day 30 was compared for both groups.
Measured: Enrolment, Day 30
Modified Rankin Scale (mRS).
The mRS is a measure of global disability that has been widely applied for evaluating recovery from stroke. Scores range from 0 to 6, with higher scores indicating greater disability. A score of 0 indicates no residual symptoms; 1 = no significant disability/able to carry out all usual activities, despite some symptoms; 2 = slight disability; 3 = moderate disability; 4 = moderately severe disability; 5 = severe disability; 6 = death. The number of participants scoring 0-2 on the mRS at Day 30 was compared in both treatment groups.
Measured: Enrolment, Day 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2008 (estimated)
- Study startAug 2008
- Primary completionApr 2011
- Study completionMay 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for StrokeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 185 participants (actual)
Sponsor and investigators
- Lead sponsor
- NoNO Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Arbor Vita Corporation
- Responsible party
- Sponsor
- Investigators
- Michael Hill, M.D., Principal investigator, Foothills Medical Centre, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00728182
- Sponsor's protocol ID
- 3302 (NA-1-002)
- Acronym
- ENACT
- Status last verified
- Aug 2013
- First submitted
- 1 Aug 2008
- Last updated
- 17 Oct 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Hill MD, Martin RH, Mikulis D, Wong JH, Silver FL, Terbrugge KG, Milot G, Clark WM, Macdonald RL, Kelly ME, Boulton M, Fleetwood I, McDougall C, Gunnarsson T, Chow M, Lum C, Dodd R, Poublanc J, Krings T, Demchuk AM, Goyal M, Anderson R, Bishop J, Garman D, Tymianski M; ENACT trial investigators. Safety and efficacy of NA-1 in patients with iatrogenic stroke after endovascular aneurysm repair (ENACT): a phase 2, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2012 Nov;11(11):942-50. doi: 10.1016/S1474-4422(12)70225-9. Epub 2012 Oct 8.
PubMed 23051991Ganesh A, Goyal M, Wilson AT, Ospel JM, Demchuk AM, Mikulis D, Poublanc J, Krings T, Anderson R, Tymianski M, Hill MD; ENACT Trial Investigators. Association of Iatrogenic Infarcts With Clinical and Cognitive Outcomes in the Evaluating Neuroprotection in Aneurysm Coiling Therapy Trial. Neurology. 2022 Apr 5;98(14):e1446-e1458. doi: 10.1212/WNL.0000000000200111. Epub 2022 Feb 15.
PubMed 35169007
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Multicenter, Randomized, Fasting, Double-Blind, Placebo-Controlled, Safety, Tolerability and Efficacy Study Evaluating a Single Dose of Intravenous NA-1 in Male and Female Patients Undergoing Endovascular Repair of Brain Aneurysms
- ClinicalTrials.gov ID
- NCT00728182
- Acronym / sponsor ID
- ENACT / 3302 (NA-1-002)
- Conditions
- Stroke
- Keywords
- Stroke, Vascular cognitive impairment, Coiling, Endovascular repair, Brain aneurysm, NA-1
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 185 participants (actual)
- Lead sponsor
- NoNO Inc.Industry (pharma, biotech, devices)
- Collaborators
- Arbor Vita Corporation
- Study start
- Aug 2008
- Primary completion
- Apr 2011 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 5 Aug 2008 (estimated)
- Results
- Posted 17 Oct 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomized, double-blind, placebo-controlled, single-dose, design investigating the safety, tolerability and efficacy of NA-1, a peptide designed to reduce ischemic brain damage. Up to 200 male and female patients undergoing endovascular repair of brain 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 Days 2-4 and end-of study procedures on Day 30. Standard safety criteria will be analysed. Efficacy endpoints include the ability of NA-1 to: 1) reduce the volume of ischemic embolic strokes, 2) reduce the number of ischemic embolic strokes, 3) reduce vascular cognitive impairment, and 4) reduce the frequency of large strokes induced by the endovascular procedure. The plasma concentrations of NA-1 will also be analyzed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NA-1 | Experimental | Drug: NA-120 amino acid peptide that consists of a 9 amino acid domain that inhibits PSD-95 and a 11 amino acid domain than enables the peptide to cross the blood-brain barrier. |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NA-1single intravenous dose of 2.6 mg/kg of NA-1 administered as a 10-minute infusion | Drug | NA-1 |
| Placebosingle intravenous dose of 2.6 mg/kg of placebo administered as a 10-minute infusion | Drug | Placebo |
Primary outcome
Volume of New FLAIR Lesions(MRI)
Time frame: Enrolment, Days 2-4
Volume of new ischemic lesions as defined by FLAIR MRI at 12-95 hours postdose
5 secondary outcomes
Number of New DWI Lesions (MRI)
Time frame: Enrolment, Day 2-4
Number of New FLAIR Lesions (MRI)
Time frame: Enrolment, Days 2-4
Volume of New DWI Lesions (MRI)
Time frame: Enrolment, Days 2-4
National Institutes of Health Stroke Scale (NIHSS).
Time frame: Enrolment, Day 30
Modified Rankin Scale (mRS).
Time frame: Enrolment, Day 30
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23051991Hill MD, Martin RH, Mikulis D, Wong JH, Silver FL, Terbrugge KG, Milot G, Clark WM, Macdonald RL, Kelly ME, Boulton M, Fleetwood I, McDougall C, Gunnarsson T, Chow M, Lum C, Dodd R, Poublanc J, Krings T, Demchuk AM, Goyal M, Anderson R, Bishop J, Garman D, Tymianski M; ENACT trial investigators. Safety and efficacy of NA-1 in patients with iatrogenic stroke after endovascular aneurysm repair (ENACT): a phase 2, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2012 Nov;11(11):942-50. doi: 10.1016/S1474-4422(12)70225-9. Epub 2012 Oct 8.
- Derived from this study: PubMed 35169007Ganesh A, Goyal M, Wilson AT, Ospel JM, Demchuk AM, Mikulis D, Poublanc J, Krings T, Anderson R, Tymianski M, Hill MD; ENACT Trial Investigators. Association of Iatrogenic Infarcts With Clinical and Cognitive Outcomes in the Evaluating Neuroprotection in Aneurysm Coiling Therapy Trial. Neurology. 2022 Apr 5;98(14):e1446-e1458. doi: 10.1212/WNL.0000000000200111. Epub 2022 Feb 15.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Hill, M.D. principal investigator
Foothills Medical Centre, University of Calgary
14 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing NA-1 in people with Stroke, run by NoNO Inc. at 14 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Oct 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Canada, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Oct 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Volume of New FLAIR Lesions(MRI) (time frame: Enrolment, Days 2-4). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00728182, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Oct 2013.