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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02930018




Registration number
NCT02930018
Ethics application status
Date submitted
6/10/2016
Date registered
11/10/2016
Date last updated
14/12/2020

Titles & IDs
Public title
Safety and Efficacy of Nerinetide (NA-1) in Subjects Undergoing Endovascular Thrombectomy for Stroke
Scientific title
A Multicentre, Randomized, Double-blinded, Placebo-controlled, Parallel Group, Single-dose Design to Determine the Efficacy and Safety of Intravenous NA-1 in Subjects With Acute Ischemic Stroke Undergoing Endovascular Thrombectomy
Secondary ID [1] 0 0
NA-1-007
Universal Trial Number (UTN)
Trial acronym
ESCAPE-NA1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stroke, Acute 0 0
Condition category
Condition code
Stroke 0 0 0 0
Haemorrhagic
Stroke 0 0 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Nerinetide (NA-1), 2.6 mg/kg
Treatment: Drugs - Placebo

Placebo Comparator: Placebo - Drug vehicle only

Experimental: Nerinetide (NA-1), 2.6 mg/kg -


Treatment: Drugs: Nerinetide (NA-1), 2.6 mg/kg
Single intravenous infusion of nerinetide over 10 ± 1 minutes

Treatment: Drugs: Placebo
Placebo Comparator: Placebo

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Subjects With mRS Score of 0 to 2 - Overall number of subjects experiencing a favorable functional outcome 90 days post-randomization, defined as 0 to 2 on the mRS.
The modified Rankin Scale (mRS) is a valid and reliable clinician-reported measure of global disability that has been widely applied for evaluating recovery from stroke. It is a scale used to measure functional recovery (the degree of disability or dependence in daily activities) of people who have suffered a stroke. mRS scores range from 0 (best outcome) to 6 (worst outcome), with 0 indicating no residual symptoms; 5 indicating bedbound, requiring constant care; and 6 indicating death.
Timepoint [1] 0 0
90 Days
Secondary outcome [1] 0 0
Number of Subjects With NIHSS Score of 0 to 2 - Number of subjects with good neurological outcome, as defined by a score of 0 to 2 on the NIHSS at Day 90 or the last rating.
The National Institutes of Health Stroke Scale (NIHSS) is a standardized neurological examination score that is a valid and reliable measure of disability and recovery after acute stroke. Scores range from 0 to 42, with higher scores indicating increasing severity.
Timepoint [1] 0 0
90 Days or the last rating
Secondary outcome [2] 0 0
Mortality Rate - Mortality rate, as defined by event rate (%) for mortality over the 90-day study period
Timepoint [2] 0 0
90 Days

Eligibility
Key inclusion criteria
1. Acute ischemic stroke (AIS) for immediate endovascular treatment

2. Age 18 or greater.

3. Onset (last-seen-well) time to randomization time within 12 hours.

4. Disabling stroke defined as a baseline National Institutes of Health Stroke Score
(NIHSS) > 5 at the time of randomization.

5. Pre-stroke (24 hours prior to stroke onset) independent functional status in
activities of daily living with modified Barthel Index (BI) > 90 (95 or 100). Patient
must be living in their own home, apartment or seniors lodge where no nursing care is
required.

6. Confirmed symptomatic intracranial occlusion, based on multiphase or dynamic
computerized tomographic angiography (CTA), at one or more of the following locations:
Intracranial carotid T/L, M1 middle cerebral artery (MCA). Functionally, when defining
the M1 or the M2, the bulk of the MCA territory must be ischemic.

7. Non-contrast computed tomography (NCCT) and CTA (multiphase or dynamic) for trial
eligibility performed or repeated at ESCAPE-NA1 stroke centre with endovascular suite
on-site.

8. Endovascular treatment with declared first endovascular approach as either stent
retriever or aspiration device, and intended to be initiated (arterial access) within
60 minutes of baseline/qualifying NCCT and to first recanalization of 90 minutes.
Study drug intended to be administered within 60 minutes of the baseline/qualifying
NCCT.

9. Signed informed consent from subject or legally authorized representative or, if
required to enable inclusion by applicable national laws and regulations and the
applicable independent review boards/Ethics Committee requirements for obtaining
consent, from the investigator after consultation with an independent physician who is
not otherwise participating in the trial.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Evidence of a large core of established infarction defined as ASPECTS 0-4.

2. Evidence of absence of collateral circulation on CTA (Collateral score of 0 or 1).

3. Intent to use any endovascular device other than a stent retriever or clot aspiration
device or intra-arterial medications as the initial thrombectomy approach.

4. Intent to use any intravenous thrombolytic other than alteplase if intravenous
thrombolysis is planned.

5. No femoral pulses, very difficult endovascular access or extreme tortuosity of great
vessels that is predicted to result in an inability to deliver timely endovascular
therapy. Direct common carotid or radial/brachial/axillary access is permissible.

6. Estimated or known weight > 120 kg or < 45 kg.

7. Pregnancy; if a woman is of childbearing potential a urine or serum beta human
chorionic gonadotropin (ß-hCG) test is positive, or breastfeeding.

8. Severe contrast allergy or absolute contraindication to iodinated contrast preventing
endovascular intervention, including any contraindications listed in the prescribing
information approved by local authorities (e.g., patients with decompensated heart
failure as a contraindication for the use of VISIPAQUEâ„¢ 270 in Germany).

9. Clinical history, past imaging or clinical judgment suggests that the intracranial
occlusion is chronic or there is suspected intracranial dissection such that there is
a predicted lack of success with endovascular intervention.

10. Prior enrolment in the ESCAPE-NA1 trial or prior receipt of NA-1 for any reason.

11. Severe known renal impairment defined as requiring dialysis (hemo- or peritoneal) or
if known a creatinine clearance < 29 mL/min.

12. Patient has a severe or fatal comorbid illness that will prevent improvement or
follow-up.

13. Patient cannot complete follow-up treatment due to co-morbid non-fatal illness or they
are known to be a visitor to the city or any other known reason for which follow-up
would be impossible (e.g. incarcerated in a federal prison).

14. Participation in another clinical trial investigating a drug, medical device, or a
medical procedure in the 30 days preceding study inclusion.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment postcode(s) [2] 0 0
- Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Rhode Island
Country [14] 0 0
United States of America
State/province [14] 0 0
Tennessee
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Washington
Country [17] 0 0
Canada
State/province [17] 0 0
Alberta
Country [18] 0 0
Canada
State/province [18] 0 0
British Columbia
Country [19] 0 0
Canada
State/province [19] 0 0
Nova Scotia
Country [20] 0 0
Canada
State/province [20] 0 0
Ontario
Country [21] 0 0
Canada
State/province [21] 0 0
Quebec
Country [22] 0 0
Canada
State/province [22] 0 0
Saskatchewan
Country [23] 0 0
Germany
State/province [23] 0 0
Dresden
Country [24] 0 0
Germany
State/province [24] 0 0
Essen
Country [25] 0 0
Germany
State/province [25] 0 0
Göttingen
Country [26] 0 0
Germany
State/province [26] 0 0
Hamburg
Country [27] 0 0
Germany
State/province [27] 0 0
Heidelberg
Country [28] 0 0
Ireland
State/province [28] 0 0
Dublin
Country [29] 0 0
Korea, Republic of
State/province [29] 0 0
Daegu
Country [30] 0 0
Korea, Republic of
State/province [30] 0 0
Incheon
Country [31] 0 0
Korea, Republic of
State/province [31] 0 0
Seoul
Country [32] 0 0
Sweden
State/province [32] 0 0
Lund
Country [33] 0 0
Sweden
State/province [33] 0 0
Stockholm
Country [34] 0 0
United Kingdom
State/province [34] 0 0
Belfast

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
NoNO Inc.
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
University of Calgary
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The ESCAPE-NA-1 study is designed to determine the safety and efficacy of the
neuroprotectant, Nerinetide (NA-1), in reducing global disability in subjects with major
acute ischemic stroke (AIS) with a small established infarct core and with good collateral
circulation who are selected for endovascular revascularization.
Trial website
https://clinicaltrials.gov/show/NCT02930018
Trial related presentations / 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.
Cook DJ, Teves L, Tymianski M. Treatment of stroke with a PSD-95 inhibitor in the gyrencephalic primate brain. Nature. 2012 Feb 29;483(7388):213-7. doi: 10.1038/nature10841.
Cook DJ, Teves L, Tymianski M. A translational paradigm for the preclinical evaluation of the stroke neuroprotectant Tat-NR2B9c in gyrencephalic nonhuman primates. Sci Transl Med. 2012 Oct 3;4(154):154ra133. doi: 10.1126/scitranslmed.3003824.
Sun HS, Doucette TA, Liu Y, Fang Y, Teves L, Aarts M, Ryan CL, Bernard PB, Lau A, Forder JP, Salter MW, Wang YT, Tasker RA, Tymianski M. Effectiveness of PSD95 inhibitors in permanent and transient focal ischemia in the rat. Stroke. 2008 Sep;39(9):2544-53. doi: 10.1161/STROKEAHA.107.506048. Epub 2008 Jul 10.
Aarts M, Liu Y, Liu L, Besshoh S, Arundine M, Gurd JW, Wang YT, Salter MW, Tymianski M. Treatment of ischemic brain damage by perturbing NMDA receptor- PSD-95 protein interactions. Science. 2002 Oct 25;298(5594):846-50.
Sattler R, Xiong Z, Lu WY, Hafner M, MacDonald JF, Tymianski M. Specific coupling of NMDA receptor activation to nitric oxide neurotoxicity by PSD-95 protein. Science. 1999 Jun 11;284(5421):1845-8.
Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, Roy D, Jovin TG, Willinsky RA, Sapkota BL, Dowlatshahi D, Frei DF, Kamal NR, Montanera WJ, Poppe AY, Ryckborst KJ, Silver FL, Shuaib A, Tampieri D, Williams D, Bang OY, Baxter BW, Burns PA, Choe H, Heo JH, Holmstedt CA, Jankowitz B, Kelly M, Linares G, Mandzia JL, Shankar J, Sohn SI, Swartz RH, Barber PA, Coutts SB, Smith EE, Morrish WF, Weill A, Subramaniam S, Mitha AP, Wong JH, Lowerison MW, Sajobi TT, Hill MD; ESCAPE Trial Investigators. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015 Mar 12;372(11):1019-30. doi: 10.1056/NEJMoa1414905. Epub 2015 Feb 11.
Public notes

Contacts
Principal investigator
Name 0 0
Michael D Hill, MD MSc
Address 0 0
University of Calgary
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications