The Efficacy of a Frequency-tuned Electromagnetic Field Treatment in Facilitating the Recovery of Subacute Ischemic Stroke Patients - a Pivotal Study (THE "EMAGINE" STUDY)
Phase: NA
Conditions: Ischemic Stroke
Sponsor: BrainQ Technologies Ltd.

 
 
The efficacy of a frequency-tuned electromagnetic field treatment in facilitating 
the recovery of subacute ischemic stroke patients – a pivotal study 
No. BQ5 
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Official Title: the efficacy of a frequency-tuned 
electromagnetic field treatment in facilitating the 
recovery of subacute ischemic stroke patients – a 
pivotal study (the “EMAGINE” study) 
Investigational medical device – BQ 2.0 
Unique Protocol Identification Number: BQ5 
 
Version Number: 4 
 
20 June 2022 
 Brief Title: EMAGINE – electromagnetic field ischemic stroke – novel 
subacute treatment  
Coordinating Investigators: Jeffrey L. Saver, MD; Pamela W. Duncan, PhD; 
Joel Stein, MD 
Sponsor: BrainQ Technologies Ltd. 
Sponsor Representative Contact Information: 
Assaf Lifshitz 
 Booth 3.7, Hi-Tech Village, Edmund J. Safra Campus, Hebrew University, 
Jerusalem, Israel 
+972 (54) 4586787 
 
assaf@brainqtech.com 
 
Sponsor Representative Signature: 
 
Confidentiality statement: This protocol is a confidential document of BrainQ Technologies Ltd.. The 
recipient of this document agrees not to disclose the information contained herein to others without prior 
written authorization of BrainQ Technologies Ltd. except that this document may be disclosed to 
appropriate Institutional Review Boards/Ethics Committees or duly authorized representatives of 
regulatory authorities, such as the U.S. Food and Drug Administration and National Competent 
Authorities in the European Union, under the condition that they maintain confidentiality. NOTE: For the 
purposes of this protocol, “ethics committee” (EC) is synonymous with “research ethics committee”, 
“independent ethics committee” or “institutional review board” (IRB). The regulatory requirements 
pertaining to ECs, IRBs, or similar institutions vary by country or region. 
 
NCT05044507

 
 
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TABLE OF CONTENTS 
− 
Statement of Compliance ..................................................................................................... 6 
− 
Statement of Investigator ...................................................................................................... 6 
1 
PROTOCOL SUMMARY ................................................................................................... 7 
1.1 
Synopsis ....................................................................................................................... 7 
1.2 
Schema ...................................................................................................................... 14 
1.3 
Schedule of Activities (SoA) ..................................................................................... 15 
2 
INTRODUCTION .............................................................................................................. 17 
2.1 
Study Rationale ......................................................................................................... 17 
2.2 
Background ............................................................................................................... 18 
2.2.1 
Summary of Findings from Nonclinical Studies of the BQ 2.0 ................ 21 
2.2.2 
Summary of Clinical Research of the BQ 2.0........................................... 23 
2.3 
Risk/Benefit Assessment ........................................................................................... 29 
2.3.1 
Known Potential Risks .............................................................................. 29 
2.3.2 
Known Potential Benefits ......................................................................... 31 
2.3.3 
Assessment of Potential Risks and Benefits ............................................. 32 
3 
OBJECTIVES AND ENDPOINTS .................................................................................... 34 
4 
STUDY DESIGN ............................................................................................................... 36 
4.1 
Overall Design ........................................................................................................... 36 
4.2 
Scientific Rationale for Study Design ....................................................................... 38 
4.3 
Justification for Dose ................................................................................................. 38 
4.4 
End of Study Definition ............................................................................................ 38 
5 
STUDY POPULATION ..................................................................................................... 39 
5.1 
Inclusion Criteria ....................................................................................................... 39 
5.2 
Exclusion Criteria ...................................................................................................... 40 
5.3 
Lifestyle Considerations ............................................................................................ 40 
5.4 
Screen Failures .......................................................................................................... 40 
5.5 
Strategies for Recruitment and Retention ................................................................. 41 
6 
STUDY INTERVENTION ................................................................................................ 44 
6.1 
Study Intervention(s) Administration ........................................................................ 44 
6.1.1 
Study Intervention Description ................................................................. 44 
6.1.1.1 
Device size(s) ....................................................................................................... 44 
6.1.1.2 
Device model(s) .................................................................................................... 44 
6.1.1.3 
Description of each component ............................................................................ 45 
6.1.1.4 
Duration of exposure ............................................................................................ 51 
6.1.1.5 
Frequency of exposure .......................................................................................... 51 
6.1.1.6 
Summary/report of test validation studies ............................................................ 51 
6.1.2 
Dosing and Administration ....................................................................... 51 
6.1.3 
Control Intervention Description .............................................................. 52 
6.2 
Preparation/Handling/Storage/Accountability .......................................................... 53 

 
 
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6.2.1 
Acquisition and accountability ................................................................. 53 
6.2.2 
Formulation, Appearance, Packaging, and Labeling ................................ 53 
6.2.2.1 
Study device ......................................................................................................... 53 
6.2.3 
Product Storage and Stability.................................................................... 53 
6.2.4 
Preparation And Handling ........................................................................ 53 
6.3 
Measures to Minimize Bias: Randomization and Blinding ....................................... 54 
6.3.1 
Allocation to Study Intervention ............................................................... 54 
6.3.2 
Blinding of Site Personnel and Subjects ................................................... 54 
6.3.3 
Blinding of the Sponsor ............................................................................ 55 
6.3.4 
Breaking the Blind .................................................................................... 55 
6.4 
Study Intervention Compliance ................................................................................. 56 
6.5 
Concomitant Therapy ................................................................................................ 56 
6.5.1 
Rescue Medicine ....................................................................................... 56 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL..................................................................................... 57 
7.1 
Discontinuation of Study Intervention ...................................................................... 57 
7.2 
Participant Discontinuation/Withdrawal from the Study .......................................... 57 
7.3 
Lost to Follow-Up ..................................................................................................... 58 
8 
STUDY ASSESSMENTS AND PROCEDURES ............................................................. 59 
8.1 
Efficacy assessments ................................................................................................. 59 
8.1.1 
Study visits ................................................................................................ 61 
8.1.1.1 
Pre-screening Phase .............................................................................................. 61 
8.1.1.2 
Screeneng & Enrollment, Baseline visit ............................................................... 62 
8.1.1.3 
Treatments 1-20 .................................................................................................... 63 
8.1.1.4 
Midterm follow-up visit (in clinic) ....................................................................... 64 
8.1.1.5 
Treatments 21-45 .................................................................................................. 65 
8.1.1.6 
Day 90 PRIMARY OUTCOME ASSESSMENT visit (in clinic) ........................ 65 
8.1.1.7 
DAY 180 ADDITIONAL follow-up visit ............................................................ 66 
8.2 
Safety and Other Assessments .................................................................................. 67 
8.3 
Adverse Events and Serious Adverse Events ............................................................ 67 
8.3.1 
Definition of Adverse Events (AE)........................................................... 67 
8.3.2 
Definition of Serious Adverse Events (SAE) ........................................... 68 
8.3.3 
Classification of an Adverse Event ........................................................... 68 
8.3.3.1 
Severity of Event .................................................................................................. 69 
8.3.3.2 
Relationship to Study Intervention ....................................................................... 69 
8.3.3.3 
Expectedness ........................................................................................................ 72 
8.3.4 
Time Period and Frequency for Event Assessment and Follow-Up ......... 72 
8.3.5 
Adverse Event and Device Deficiency Reporting .................................... 72 
8.3.6 
Serious Adverse Event Reporting ............................................................. 74 
8.3.7 
Reporting Events to Participants ............................................................... 75 
8.3.8 
Events of Special Interest.......................................................................... 75 
8.3.9 
Reporting of Pregnancy ............................................................................ 75 

 
 
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8.4 
Unanticipated Problems ............................................................................................ 76 
8.4.1 
Definition of Unanticipated Problems (UP) ............................................. 76 
8.4.2 
Unanticipated Problem Reporting............................................................. 77 
8.4.3 
Reporting Unanticipated Problems to Participants ................................... 77 
9 
STATISTICAL CONSIDERATIONS ............................................................................... 77 
9.1 
Statistical Hypotheses ................................................................................................ 77 
9.2 
Sample Size Determination ....................................................................................... 78 
9.3 
Populations for Analyses ........................................................................................... 78 
9.4 
Statistical Analyses .................................................................................................... 79 
9.4.1 
General Approach ..................................................................................... 79 
9.4.2 
Analysis of the Primary Endpoint ............................................................. 80 
9.4.3 
Analysis of the Secondary Endpoint(s)..................................................... 81 
9.4.4 
Safety Analyses ......................................................................................... 82 
9.4.5 
Baseline Descriptive Statistics .................................................................. 82 
9.4.6 
Planned Interim Analyses ......................................................................... 82 
9.4.7 
Sub-Group Analyses ................................................................................. 84 
9.4.8 
Tabulation of Individual participant Data ................................................. 85 
9.4.9 
Exploratory Analyses ................................................................................ 85 
9.4.10 
Adherence and Retention Analyses .......................................................... 85 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ..... 86 
10.1 
Regulatory, Ethical, and Study Oversight Considerations ........................................ 86 
10.1.1 
Informed Consent Process ........................................................................ 86 
10.1.1.1 
Consent/assent and Other Informational Documents Provided to participants .... 86 
10.1.1.2 
Consent Procedures and Documentation .............................................................. 86 
10.1.2 
Study Discontinuation and Closure .......................................................... 88 
10.1.3 
Confidentiality and Privacy ...................................................................... 89 
10.1.4 
Future Use of Stored Specimens and Data ............................................... 91 
10.1.5 
Key Roles and Study Governance ............................................................ 91 
10.1.6 
Safety Oversight........................................................................................ 92 
10.1.7 
Clinical Monitoring ................................................................................... 92 
10.1.8 
Quality Assurance and Quality Control .................................................... 93 
10.1.9 
Data Handling and Record Keeping ......................................................... 93 
10.1.9.1 
Data Collection and Management Responsibilities .............................................. 93 
10.1.9.2 
Study Records Retention ...................................................................................... 98 
10.1.10 
Protocol Deviations ................................................................................... 99 
10.1.11 
Publication and Data Sharing Policy ...................................................... 101 
10.1.12 
Conflict of Interest Policy ....................................................................... 102 
10.2 
Additional Considerations ....................................................................................... 102 
10.3 
Abbreviations .......................................................................................................... 103 
10.4 
Protocol Amendment History .................................................................................. 106 

 
 
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11 
REFERENCES ................................................................................................................. 110 
12 
APPENDICES .................................................................................................................. 122 
12.1 
Appendix 1 – Questionnaires and functional test .................................................... 122 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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− 
STATEMENT OF COMPLIANCE 
The trial will be conducted in accordance with: a) the Helsinki Declaration adopted by the 18th World 
Medical Assembly in Helsinki, Finland, in 1964, as last amended by the World Medical Assembly; b) the 
International Conference on Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human Use (ICH) Harmonised Tripartite Guideline for Good Clinical Practice 
(GCP) E6 (R2); c) the ISO 14155 standard, to the extent of recognition by the local regulations, and, 
where applicable; d) 21 CFR Parts 11, 50, 54, 56, 812; 45 CFR Parts 46 and 160; European Union (EU) 
Directive 93/42/EEC and, once applicable, Regulation 2017/745. 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the Institutional Review Board (IRB) / Ethics Committee (EC) for review and approval. 
Approval of both the protocol and the consent form will be obtained before any participant is 
consented/enrolled. Any amendment to the protocol will require review and approval by the IRB/EC 
before the changes are implemented to the study. All changes to the consent form will be approved by the 
IRB/EC; a determination will be made regarding whether a new consent needs to be obtained from 
participants who provided consent using a previously approved consent form. 
The Sponsor has taken out an insurance policy for the total duration of the study covering the patients and 
Investigators with respect to the risks involved in conducting this study according to this protocol. 
Sponsor: 
____________________ 
 
 
 
Print/Type Name: 
Signature: 
__________________________ 
Date: 
_________________________ 
− 
STATEMENT OF INVESTIGATOR 
I agree to perform the investigations and to abide by this protocol and assure that no deviation from, or 
changes to the protocol will take place without prior agreement from the Sponsor or Sponsor's 
representative and documented approval from the IRB/EC, except where necessary to eliminate an 
immediate hazard(s) to the study participants. 
I agree to ensure that all staff members involved in the conduct of this study are informed about their 
obligations in meeting the above commitments, are appropriately trained, have read the Protocol, 
Instructions for Use (IFU) and, where required, United States (U.S.) Code of Federal Regulations (CFR) 
applicable to clinical studies listed above. All personnel involved in the conduct of this study and 
authorized to perform the study-related tasks/procedures have completed GCP training and, if applicable, 
Human Subjects Protection Training, and are authorized to perform the study-related tasks/procedures. 
Although I may have delegated trial-related duties, as the Principal Investigator, I maintain full 
responsibility for this trial. 
Principal Investigator: 
____________________ 
 
 
 
Print/Type Name: 
Signature: 
__________________________ 
Date: 
_________________________ 

 
 
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1 
 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS 
 
Title: 
The efficacy of a frequency-tuned electromagnetic field treatment in facilitating 
the recovery of subacute ischemic stroke patients – a pivotal study (the 
“EMAGINE” study) 
Unique Protocol 
Identification 
Number 
BQ5 
Study Design 
Prospective, multicenter, double-blind, randomized, sham-controlled, parallel two-
arm study, following a sample-size–adaptive design with a single planned interim 
analysis. 
Study Phase 
Pivotal 
Sponsor 
Representative 
Israel: Assaf Lifshitz, VP of Operations, 3.7 Hi-Tech Village, Edmund J. Safra 
Campus, Hebrew University, Jerusalem, Israel; Phone +972 (54) 4586787; E-mail: 
assaf@brainqtech.com 
Investigational 
Device Name 
BQ 2.0 
Investigational 
Device 
Description and 
Regulatory 
Classification 
BQ 2.0 is a wearable medical device that produces and delivers non-invasive, 
extremely-low–intensity and low-frequency, frequency-tuned electromagnetic 
fields in order to stimulate neuronal networks with the aim of reducing disability 
and promoting neurorecovery. 
The technology behind the therapy utilized explanatory machine learning and 
Brain-Computer Interface tools to identify high-resolution spectral patterns that 
characterize motor functions; the tools are based on a large database of 
electroencephalography (EEG) spectra taken during functional motor tasks. These 
spectral patterns are then translated into a non-invasive electromagnetic field 
treatment, which applies similar patterns directly to the patient’s central nervous 
system (CNS). 
Investigational 
Device Use in 
the Study: 
In this study, BQ 2.0 is intended to reduce disability in adult patients with subacute 
ischemic stroke, with a moderate to severe disability which includes an upper 
extremity motor impairment. 
BQ 2.0 will be used for 9 weeks in conjunction with physical and occupational 
therapy (PT/OT) and under periodic supervision (either remote or in-person) of a 

 
 
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trained site study team member. Treatments may be administered in multiple 
settings [eg, acute care hospital (ACH), inpatient rehabilitation facilities (IRF), 
Skilled Nursing Facility (SNF), home or other outpatient setup]. 
Study 
Population: 
The study will enroll up to 150 adult patients with subacute ischemic stroke, with a 
moderate to severe disability which includes an upper extremity motor impairment, 
who will be assigned (1:1 allocation ratio) to either active or sham study 
intervention using BQ 2.0, initiated 4-21 days after the index stroke event. 
Following the interim analysis, the sample size may be increased up to 344 
subjects. Total enrollment from each site to be no more than 20% of the total 
sample size. 
Study 
Description: 
The study intervention will be initiated 4-21 days after the index stroke event and 
will consist of a total of 45 sessions over a period of 9 weeks (5 treatments per 
week). Each session will last 60 minutes during which 40 consecutive minutes of 
active or sham study intervention using BQ 2.0 will be administered. Each study 
group will be guided by the BQ 2.0 application and asked to perform a 
standardized, pre-defined and evidence-based physical and occupational therapy 
regimen concurrent with the study intervention. The PT/OT regimen applied in 
both treatment and sham controlled groups is aligned with the Class 1 level A 
recommendation for patients with stroke to participate in a home-based 
rehabilitation program.1 
 
BQ 2.0 does not produce any noticeable sound, light or sensation in connection 
with the stimulation which may disclose the arm assignment, making it ideal for 
testing in a sham-controlled setup. During sham treatment sessions, for purposes of 
maintaining the blind, the device will function as if it is delivering the therapy (i.e., 
the device will turn on and all indicators will function), but the frequency and 
intensity parameters that are not visible to the subject or site study members will be 
set to zero so that no stimulation is delivered. 
Screening phase 
Prospective subjects, who are 3 to 21 days post-stroke, will be consented to 
participate in the study at either: 
a) a participating ACH, prior to anticipated transfer to a participating IRF, 
SNF, outpatient, or home setting; or  
b) at a participating IRF, SNF, outpatient, or home setting. 
 
1 Winstein CJ, Stein J, Arena R, et al. Guidelines for Adult Stroke Rehabilitation and Recovery. Stroke 2016; 47: 
e98–e169. 

 
 
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Consented subjects, who are 4 to 21 days post-stroke will be screened for 
eligibility to participate in the treatment phase of the study. 
Efforts should be made to complete enrolment, randomization and initiate 
treatments as early as possible within the window of recruitment, and target to 
complete a first treatment within 4 weekdays from admission to the participating 
site.  
 
Treatment Phase 
Eligible subjects will be randomly assigned, at a 1:1 allocation ratio, to either the 
active or sham study intervention groups. 
 
Randomized patients will receive active or sham study intervention sessions using 
BQ 2.0 (active or sham therapy, respectively), starting 4-21 days after stroke onset 
and no later than 2 days after randomization. Sessions will be conducted 5 times a 
week. Each session will last ~60 minutes, with active or sham field being turned on 
for up to 40 minutes. The only difference between the BQ 2.0 active stimulation 
and sham therapy is that the sham device does not generate electromagnetic fields 
during treatment. Subjects in both the active intervention group (BQ 2.0 group) 
and sham group will be asked to perform device guided physical and occupational 
therapy activities during each session. Participation in the study will not replace 
any of the usual care patient should receive.  
 
During the study, 45 sessions of active or sham therapy will be conducted in either 
inpatient, outpatient or home setting.  
 
A trained member of the site study team (the “Clinic Operator”) will be 
responsible for training and approving the subject’s caregiver to operate the session 
independently.  
 
Before an approval to operate a session independently (the “Approval”) is granted 
by the Clinic Operator, a Clinic Operator will train the caregiver and supervise the 
sessions, either in-person or remotely. Once an Approval was granted, sessions 
will be conducted with the assistance of a caregiver while the Clinic Operator will 
provide periodic oversight (combined audio and video remote conferencing or 
audio only, if video is not available). If needed, and at their discretion, the Clinic 
Operator may join sessions following the Approval too.   
 
Any adverse events and device deficiencies occurring during the period of 
subject’s participation will be recorded. 
 

 
 
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Subjects will undergo a detailed interim outcome assessment on the 20th (±4) day 
of treatment, and a detailed primary endpoint outcome assessment on the 90th (±15) 
day after the onset of the index stroke. In addition, a focused, long-term outcome 
assessment on the 180th (±15) day after the onset of the index stroke will be 
performed. 
Objectives: 
Primary Efficacy  
To show that the BQ therapy is effective in reducing global disability at 3 months 
post-stroke in disabled patients with upper limb motor impairment when initiated 4 
to 21 days following an ischemic stroke. 
 
Secondary Efficacy  
To show that the BQ therapy is effective in reducing upper and lower limb 
impairment, and improving upper limb functionality, health-related quality of life 
(HRQoL), and level of participation in instrumental activities of daily living 
(ADL) at 3 months post-stroke, when initiated 4 to 21 days following an ischemic 
stroke. 
 
Safety 
1. To characterize the safety profile of the BQ therapy. 
2. To show that the BQ 2.0 performs reliably 
Tertiary/Exploratory 
1. To show that the BQ therapy is effective in reducing cognitive impairment, 
depression and fine-grained level of disability at 3 months post-stroke, when 
initiated 4 to 21 days following an ischemic stroke. 
2. To characterize the long-term effect at 6 months post-stroke of the BQ therapy 
effect on upper limb functionality and health-related quality of life (HRQoL).   
3. To formally evaluate the cost-effectiveness of the BQ therapy over a lifetime 
horizon from the perspective of the United States healthcare system. 
4. To explore the relationship between adherence to treatment as measured by the 
Qompass and clinical outcomes 
Endpoints: 
Primary efficacy endpoint 
Modified Rankin Scale (mRS; global disability) change from baseline (4-21 days 
post-stroke) to 90 days post-stroke. 
 
Secondary efficacy endpoints 

 
 
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The secondary efficacy endpoints will be analyzed in stepwise gatekeeper manner 
to control for multiplicity. The hierarchical order of analysis will be: 
1. Lead secondary endpoint: Fugl-Meyer Assessment for Upper Extremity 
(FMA-UE; upper limb function) – change from baseline (4-21 days post-
stroke) to 90 days post-stroke 
2. Box and Block Test (arm motor function) – change from baseline (4-21 
days post-stroke) to 90 days post-stroke. 
3. 10-meter Walk Test (gait speed) – change from baseline (4-21 days post-
stroke) to 90 days post-stroke  
4. Stroke Impact Scale Hand Domain (patient-reported hand function) – 
change from baseline (4-21 days post-stroke) to 90 days post-stroke. 
5. Stroke Impact Scale 16 (patient-reported physical functional limitation) – 
change from baseline (4-21 days post-stroke) to 90 days post-stroke. 
6. 5-level EQ-5D (health-related quality of life) at 90 days post-stroke. 
Safety 
1. Serious procedure– or device–related adverse events. 
2. Device deficiencies to detect operational reliability. 
Tertiary/Exploratory 
1. Montreal Cognitive Assessment (global cognitive function) – at 90 days post-
stroke. 
2. Patient Health Questionnaire-8 (depression) – at 90 days post-stroke. 
3. Academic Medical Center Linear Disability Scale (granular level of disability) 
at 90 days post-stroke. 
4. Modified Rankin Scale (global disability) change from baseline (4-21 days 
post-stroke) to 180 days post-stroke. 
5. Stroke Impact Scale Hand Domain (patient-reported hand function) – change 
from baseline (4-21 days post-stroke) to 180 days post-stroke. 
6. 5-level EQ-5D (health-related quality of life) at 180 days post-stroke. 
7. Formal cost-effectiveness analysis over a lifetime horizon from the perspective 
of the United States healthcare system.  
8. Relationship between adherence to treatment as measured by the Qompass and 
the clinical outcomes  
Eligibility 
Criteria 
Inclusion criteria: 
1. mRS score of 3 or 4. 
2. FMA-UE score between 10-45 (inclusive) of impaired limb. 
3. Age 22 to 85 years of age (inclusive). 

 
 
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4. Diagnosed with an ischemic stroke, confirmed by CT2 or MRI3 imaging. 
5. Four to 21 days from stroke onset (or last known well).  
6. Pre-stroke mRS of 0 or 1. 
7. Able to sit with the investigational device for 40 consecutive minutes, in 
the opinion of the investigator or designee. 
8. Can follow a 3-step command, such as “take the paper, fold it in half, and 
return it to me”. 
9. Willingness to participate in occupational/physical therapy activities 
during study intervention sessions. 
10. Availability of a relative or other caregiver able to assist during PT/OT 
treatment, and to operate an application installed on a mobile device, 
including a video call. 
11. If female, not pregnant (as confirmed by a urine or a blood test, or as 
determined by an official medical document) or breastfeeding and with no 
ability to become pregnant or on an acceptable method of contraception 
during the study. 
12. Informed consent signed by subject (if competent) or legally authorized 
representative. 
Exclusion criteria: 
1. Severe neglect impairment (NIHSS4 item 11, score = 2) or neglect that is 
severe enough to interfere with reasonable performance of study 
procedures.  
2. Implanted active electronic or passive MR-incompatible devices. 
3. Previous ischemic or hemorrhagic stroke within  2 weeks before the index 
stroke. 
4. Pre-existing neurological condition (eg, Alzheimer’s disease, Parkinson’s 
disease, multiple sclerosis, traumatic brain injury, spinal cord injury) or 
physical limitation that would interfere significantly with the subject’s 
participation in the study and/or confound neurological or functional 
evaluation. 
5. Active epilepsy or currently taking anti-epileptic medication (indicated for 
the treatment of a seizure disorder), or seizure in the last 5 years. 
6. Significant visual disturbances that cannot be corrected and that would 
interfere significantly with the subject’s participation in the study and/or 
confound neurological or functional evaluation. 
7. Unstable serious illness/condition (eg; active cancer, severe heart failure, 
active psychiatric condition) or life expectancy of less than 12 months. 
 
2 Computed tomography 
3 Magnetic resonance imaging 
4 National Institutes of Health Stroke Scale 

 
 
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8. A known severe allergic reaction to acrylic-based adhesives. 
9. Ongoing alcohol abuse and/or illicit drug use. 
10. Participation in another trial that would conflict with the current study or 
clinical endpoint interference may occur. 
11. Employee of the Sponsor. 
12. Prisoner. 
Description of 
Sites/Facilities 
Enrolling 
Participants: 
This is a multicenter study that will be conducted at approximately 20 centers.  
Study Duration: 
Estimated time to complete enrollment: 24 months 
Estimated time from study initiation until completion of data analyses: 33 months. 
Participant 
Duration: 
From 3-21 days post stroke until 180 (±15) days post-stroke. 
Statistical 
Considerations 
Full details of the statistical analysis plan are presented in the statistical section of 
the protocol, including definition of analysis sets, alpha level handling and 
adjustments for multiplicity, poolability, etc.  
 
Statistical hypothesis 
Null hypothesis: 
Mean change in mRS score from baseline (post-stroke day 4-21) to 90 days post-
stroke in the BQ 2.0 group = mean change in the sham group. 
Alternative hypothesis: 
Mean change in mRS score from baseline (post-stroke day 4-21) to 90 days post-
stroke in the BQ 2.0 group ≠ mean change in the sham group. 
 
Interim analysis 
One interim analysis is planned after 61% evaluable participants have completed 
the 90-day visit with rules for sample size reassessment or stopping for futility. 
 
 
 

 
 
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1.2 
SCHEMA 

 
 
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1.3 
SCHEDULE OF ACTIVITIES (SOA) 
 
Procedures 
Pre-
Screening 
Phase  
Screening, 
Enrollment & 
Baseline Visit 
 
 
Treatments 
1-20  
Midterm 
follow-
up (in 
clinic5) 
± 4 days 
from 20th 
treatment) 
Treatments 
21-456  
 
 90 Day 
Primary outcome 
assessment (in 
clinic7) 
90 Day ± 15 days 
post-stroke  
Additional 
follow-up 
(remote) 
180 Day 
± 15 days 
post-stroke  
Informed consent 
 
X 
 
 
 
 
 
modified Rankin Scale (mRS) 
 
 X8 
 
X 
 
X 
X 
Inclusion/exclusion criteria review 
X9  
 X10 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
Investigational/sham device use and 
intra-session PT/OT 
 
 
X 
 
X 
 
 
Fugl-Meyer Assessment for Upper 
Extremity (FMA-UE) 
 
 X 
 
X 
 
X 
 
Box and Block Test (BBT) 
 
X 
 
X 
 
X 
 
Stroke Impact Scale (SIS) Hand 
Domain 
 
X 
 
X 
 
X 
X 
Stroke Impact Scale 16 (SIS-16) 
 
X 
 
X 
 
X 
 
10 Meter Walk Test (10MWT) 
 
X 
 
 
 
X 
 
Shoulder Abduction and Finger 
Extension (SAFE) score 
 
X 
 
 
 
 
 
5-level EQ-5D (EQ-5D-5L) 
 
 
 
 
 
X 
X 
Montreal Cognitive Assessment test 
(MoCA) 
 
 
 
 
 
X 
 
 
5 In special circumstances and subject to the approval of the Principal Investigator, visit can be conducted in an outpatient setting or via combined audio and video remote conferencing or audio only, if 
video is not available.   
6 Missed or incomplete treatment sessions can be completed up until the day before the 90 Day follow up visit (day 90 ±15). 
7 In special circumstances and subject to the approval of the Principial Investigator, visit can be conducted in an outpatient setting or via combined audio and video remote conferencing or audio only, if 
video is not available.  
8 To be performed after consenting and before all other screening activities. 
9 Brief review to determine initial eligibility for and interest in the study  
10 mRS and FMA-UE are to be performed again before randomization if more than 24 hours have elapsed since the assessment of the mRS and FMA-UE. If assessments are performed again and 
subject is eligible, the later scores will serve as the baseline scores and for stratification.  

 
 
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Patient Health Questionnaire-8 (PHQ-
8) 
 
 
 
 
 
X 
 
Academic Medical Center Linear 
Disability Scale (ALDS) 
 
 
 
 
 
X 
 
Health economics data capture  
 
 
 
X 
 
X 
X 
Demographics 
 
X 
 
 
 
 
 
Medical history 
 
X 
 
 
 
 
 
Concomitant medications review and 
evaluation 
 
X 
X 
X 
X 
X 
X 
Vital signs 
 
X 
 
X 
 
X 
 
Pregnancy test11 
 
X 
 
 
 
 
 
Adverse events review and evaluation 
 
X 
X 
X 
X 
X 
X 
PT/OT done outside of study review 
 
 
X 
X 
X 
X 
 
Investigational/sham device use 
 
 
X 
 
X 
 
 
Blinding effectiveness assessment 
 
 
  
 
 
X 
 
Device deficiencies review and 
evaluation 
 
 
X 
X 
X 
X 
 
National Institutes of Health Stroke 
Scale (NIHSS) score 
 
X 
 
 
 
 
 
Transcription of last mRS score given 
as part of routine care prior to 
discharge from ACH 
 
X12 
 
 
 
 
 
Transcription of blood count13 
 
X 
 
 
 
 
 
Provision of imaging data1415 
 
X 
 
 
 
 
 
Complete case report forms 
 
X 
X 
X 
X 
X 
X 
 
11 In women of childbearing potential, a urine or a blood test, or based on official medical documentation. 
12 To be retrieved after consenting; this score will not serve as the baseline mRS score. 
13 Limited to transcription of red blood cell distribution width and absolute white cell count values from the blood count performed at the time of admission into the Intensive Care Unit (ICU) or ACH 
(the earlier available of the two). 
14 Provision of Digital Imaging and Communications in Medicine (DICOM) files obtained from all computed tomography (CT), CT angiography (CTA), CT perfusion (CTP), and brain magnetic 
resonance imaging (MRI) perfusion/diffusion-weighted imaging (DWI/PWI) / fluid attenuated inversion recovery brain magnetic resonance angiography (FLAIR), and brain magnetic resonance 
angiography (MRA) studies available from the first 7 days in the ACH. 
15 If multiple images are available from different days/recording sessions at the acute stay, collect the first image (must) and the last image. MRI images are preferred over CT 
 

 
 
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2 
 
INTRODUCTION 
2.1 
STUDY RATIONALE 
Stroke is a leading cause of major adult disability in the United States. The preponderance of 
strokes in the US (80%-87%) are ischemic, with a smaller proportion hemorrhagic (1, 2). 
Effective interventions exist for ischemic stroke in the acute phase. These include recanalization 
therapies, such as intravenous thrombolysis (IVT) with alteplase (3-12) and mechanical 
endovascular thrombectomy (EVT; (13, 14)). However, these therapies are available to only a 
relatively small subset of patients (5%-15%) and within a relatively short post-event–onset 
window (15). Moreover, even among patients treated with combined IVT and EVT, 73% have a 
disabled or fatal outcome at three months (16). 
Beyond acute care, stroke rehabilitation is the focus, a combined and coordinated use of medical, 
social, educational, and vocational measures to retrain individuals who have suffered strokes that 
resulted in life-limiting disability. Hemiparesis (weakness or inability to move on one side) and 
upper limb motor impairment are some of the most common disabling symptoms of stroke (17). 
As many as 88% of patients with acute stroke have hemiparesis (18). Ample evidence supports 
the premise that early initiation of physical therapy favorably influences motor recovery from 
stroke (19). It is recognized that highly intensive and highly repetitive physical therapeutic 
programs probably provide direct influence on the process of functional reorganization in the 
brain and enhance neurologic recovery (20). A key aspect of neuroplasticity that has important 
implications for rehabilitation is the fact that the modifications in neuronal networks are use-
dependent. Animal experimental studies and clinical trials in humans have shown that forced-use 
and functional training contribute to improved function, emphasizing the benefit of intense 
physical therapy regimens as a treatment of stroke symptoms (21). Additionally, experimental 
evidence indicates that plasticity can be altered by external factors, including pharmacologic 
agents, electrical stimulation, and environmental stimulation (22). 
Nonetheless, despite receiving current standard of care rehabilitation therapy, a large proportion 
of stroke patients finish their rehabilitation therapy course with residual and substantial deficits, 
including in the upper limb.  
Consequently, although there are demonstrated benefits of select acute ischemic stroke therapies 
and rehabilitation programs, many stroke patients are left with persisting, lifelong impairments. 
This trial tests a promising new intervention to promote post-stroke neural reorganization and 
functional recovery. Multiple studies have shown that exposing impaired neuronal networks to 
oscillating fields that are similar to those experienced in a healthy central nervous system, 
promotes network reorganization post-injury. The cardinal frequencies of these oscillations have 

 
 
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been identified using electroencephalographic recordings of healthy and impaired populations. 
The BQ 2.0 device transmits these frequencies via non-invasive, extremely-low–intensity, low-
frequency electromagnetic field exposure (BQ therapy). These frequency-tuned exposures are 
within the same frequency and intensity ranges as those fields generated about the neurons in an 
active network. As network dynamics have been shown to be sensitive to endogenous (23, 24) 
and external electric and magnetic fields at specific frequencies (24-26), this treatment is 
designed to support the return of synchronization within the targeted networks and, ultimately, 
network reorganization. 
The BQ 2.0 device is intended to be used adjunctively with the current standard of care. During 
the exposure to the device generated electromagnetic fields (BQ therapy), patients perform 
device-guided physical and occupational exercises to further support their recovery process and 
drive neural reorganization. The exercises patients are asked to perform during BQ therapy are 
evidence-based PT and OT regimens focused on upper extremity rehabilitation. 
Initial clinical studies suggest that the BQ therapy started subacutely after ischemic stroke may 
decrease the degree of disability in stroke patients. The study to be conducted under this protocol 
is designed to confirm the initial findings and provide evidence of efficacy and safety of the BQ 
2.0 in treatment of ischemic stroke patients. 
2.2 
BACKGROUND 
Ischemic stroke is injury to the brain due to vessel occlusion, depriving a brain region of blood 
flow carrying oxygen and nutrients (27). Ischemic stroke accounts for the great preponderance 
(80%-87%) of all stroke in the United States, with hemorrhagic stroke, injury to the brain due to 
vessel rupture, causing the remainder (1, 2). Etiologically, ischemic stroke is caused most often 
by embolism from the heart, artery-to-artery embolism, and in-situ small vessel disease. In one-
fifth of cases, the cause is cryptogenic (28). 
Ischemic stroke is a leading cause of long-term disability and patient mortality worldwide (29). 
Overall, stroke accounts for almost 5% of all disability-adjusted life-years (30) and 10% of all 
deaths worldwide (31). In the United States, over 795 000 strokes occur each year (2), of which 
approximately 610 000 are first attacks, and 185 000 are recurrent strokes. Stroke claims more 
than 150 000 lives annually but leaves even more patients alive but disabled. About 7 million 
post-stroke survivors live in the United States (32) and about 2.5% of its population report 
disability due to stroke. The impact of stroke to the United States economy, including the cost of 
health care services, medicines to treat stroke, and missed days of work, is over $45 billion (33, 
34) and is forecasted to grow substantially, in parallel to the expected increase of 20% in 
ischemic stroke incidence by 2030 (33). 

 
 
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The leading effective interventions for ischemic stroke in the acute phase (first 0-24h) are 
reperfusion treatments – IVT with alteplase (3-12) and EVT (13, 14). However, these therapies 
are available to only a relatively small subset of patients (5%-15%) and within a relatively short 
post-event–onset window (15). Moreover, though of proven benefit, these treatments are far 
from a panacea. Even among patients treated with combined IVT and EVT, 73% have a disabled 
or fatal outcome at three months (16). 
Importantly, the effect of acute ischemic stroke treatments upon final 3-month disability outcome 
is determined by early clinical and imaging outcomes at 24-96 hours. At least 8 multicenter trials 
and registries studies, enrolling a collective total of 10 494 acute ischemic stroke patients treated 
with supportive care, IV thrombolysis, and/or endovascular thrombectomy have found that the 
dominant independent early predictors of 3-month disability outcome are patient age, extent of 
neurologic deficits at 24-48 hours on the NIHSS, and infarct extent at 24-48 hours (35-42). 
Reperfusion therapy has no independent influence on the trajectory of patient recovery, in terms 
of disability, from 48 hours to day 90 (35). 
The initial evaluation and management of ischemic stroke patients in ACHs typically lasts 
between 2-9 days (median 4-5 days). Ischemic stroke patients are then discharged to one among 
a range of continued care settings, including their own homes, IRFs), and skilled nursing 
facilities (SNFs; (43)). The standard of care for ischemic patients in the subacute and chronic 
stages has two main elements. The first is medical and surgical therapies to prevent recurrent 
stroke, including administering anti-thrombotic agents and controlling key modifiable risk 
factors. The second is rehabilitation therapy to maximize recovery from the index stroke. 
Rehabilitation therapies are functional and impairment-specific, focusing on the areas of loss 
which are individual to each patient (44). 
In the case of motor impairment, one of the most common and devastating deficits after stroke, 
extensive OT and PT regimens are regularly implemented, focusing on individual areas of gross 
and fine motor impairment. PT/OT typically involves a variety of specific motor skill exercises, 
mobility training, range of motion therapy and constraint-induced mobility therapy (CIMT). The 
recommendation is that physical rehabilitation be initiated as early as is tolerated after the first 
24 hours from stroke onset (19). The intensity of therapy depends on patient ability as well as 
treatment setting. There is strong evidence for benefit from PT/OT interventions involving 
highly intensive and highly repetitive task-oriented and task-specific training (20). CIMT has 
been found to be moderately effective and recommended as part of PT/OT regimens for 
appropriate patients (45). 
Direct motoric and cognitive interaction with a physical and occupational therapist remains the 
mainstay of rehabilitation therapy for residual motor impairment in the United States. Among 
ischemic stroke patients with a moderate to severe disability at the end of the acute care hospital 

 
 
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phase, multiple studies have demonstrated the typical subsequent course is some improvement in 
deficits over the next 3 months followed by stabilization at a permanent level of functioning. 
Multiple studies have shown that, with standard rehabilitative care, moderately-severely disabled 
patients improve by a mean of around 1.1 points on the mRS scale by day 90 (46-48). Taking 
into account this improvement, the mRS level at the conclusion of acute care, upon stabilization 
from acute injury is strongly and consistently correlated with mRS at day 90 (49). This 
improvement is consistent across broad patient groups, regardless of age, sex, and ischemic 
stroke mechanism. However, this improvement is typically incomplete, and most patients are 
then left with residual, permanent disability. 
Some technologies have been tested, generally in small trials, for potential to further improve 
recovery above this standard of care, including neuromuscular electrical stimulation (NMES), 
functional electrical stimulation (FES), and robot-assisted therapy (50, 51). Although of some 
promise, none of these devices has been yet demonstrated to be unequivocally beneficial and 
none are deemed to be elements in the current standard of care in the United States (43). 
In sum, although there are demonstrated benefits of select acute ischemic stroke therapies and 
PT/OT rehabilitation programs for stroke, a substantial majority of stroke patients, roughly 90% 
(2), are left with persisting, lifelong impairments despite receiving the current standard of care. 
Thus, while the standard of care may be effective and allow for a meaningful reduction in 
disability, for those patients with a moderate to severe disability, these changes are often 
insufficient. In these patients, a chronic disability persists, not allowing them to return to work or 
participate in their usual pre-stroke activities. 
Potential role of the investigational device 
In the subacute phase after ischemic stroke, the central nervous system (CNS) attempts to repair 
and reorganize itself by reorganizing damaged networks and forging new connections to restore 
motor and cognitive functions (52-54). Following injury, and before such reorganization takes 
place, neuronal network connectivity is disturbed, which is reflected in perturbed oscillatory 
patterns on electroencephalography (EEG; (53, 55, 56)). 
The mechanism of action proposed by BrainQ Technologies Ltd. is that exposing impaired 
neuronal networks to oscillating fields that are similar to those experienced in a healthy CNS, 
promotes network reorganization post-injury. The cardinal frequencies of these oscillations are 
identified using EEG recordings of healthy and impaired populations, and transmitted via non-
invasive, extremely-low–intensity, low-frequency electromagnetic field exposure 
(Electromagnetic Network Targeting Field or ENTF; BQ therapy). These frequency-tuned 
exposures are within the same frequency and intensity ranges as those fields generated about the 
neurons in an active network. As network dynamics have been shown to be sensitive to 

 
 
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endogenous (23, 24) and external electric and magnetic fields at specific frequencies (24-26), 
this treatment is designed to support the return of synchronization within the targeted networks 
and, ultimately, network reorganization. 
In order to identify oscillatory patterns in the healthy CNS, most relevant to our treatment, BQ 
2.0 utilizes explanatory (supervised) machine learning (ML) tools on labeled EEG data, recorded 
during specific motor paradigms.  
Supervised learning is a ML technique, which uses labeled data, in which the correct output 
(label) is given to the algorithm in conjunction with every input sample (57). The goal of this 
technique is to determine a function or model, referred to as the classifier or the regressor, that 
can predict the correct output for every input in a novel dataset.  
Supervised learning is used as a tool to analyze EEG recordings, primarily for diagnostic 
purposes of neurological conditions such as epilepsy (58-60). This method requires the design of 
a paradigm to allow for the collection of labeled EEG data. In such cases, the goal of the 
classification algorithm is to predict the patient’s condition with maximum accuracy. The 
features that contribute to the classification are usually of limited interest and are often not 
readily interpretable.  
In contrast, when explanatory ML tools are used, the focus is analyzing the features that are most 
informative to the classification. This approach may reveal biological insights (61). 
Taken together, BrainQ Technologies Ltd. used explanatory ML to extract spectral 
features/patterns to inform the frequency selection of the BQ therapy. To identify these features, 
BrainQ Technologies Ltd. collected large quantities of labeled EEG data from both healthy and 
impaired individuals while performing specific motor tasks. The data underwent preprocessing, 
subsequently, a supervised learning classifier was trained to achieve high classification accuracy 
between different states (ie, hand grip vs. rest) and identified specific features critical to each 
state. BrainQ Technologies Ltd. then incorporated prior knowledge to selectively identify a 
subset of the extracted features most relevant to neurological recovery to inform the BQ therapy 
frequencies. The frequency identification analysis has already been completed for this version of 
the device and it is static. 
2.2.1 SUMMARY OF FINDINGS FROM 
NONCLINICAL STUDIES OF THE BQ 2.0 
The pre-clinical studies performed with the BQ 2.0 are shortly tabulated below (Table 1). For a 
detailed summary, please refer to the study investigator’s brochure (IB). 

 
 
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Table 1. Short summary of pre-clinical evaluation of the BQ 2.0 
Test Name 
Objectives and Endpoints 
Verification Methods 
Sample Size Main Results 
BRQ-001-EF 
The Influence of 
Electromagnetic 
Exposure on 
Neurogenesis in 
Mice 
Objectives: 
To assess the efficacy of 
extremely low frequency (ELF) 
magnetic fields exposure on 
neurogenesis in adult mice. 
Endpoints: 
Body weight (1/week), clinical 
signs, morbidity and mortality 
(2x/day), Social recognition, 
gross pathology), histological 
analysis. 
When possible, scores 
were analyzed by two-
way ANOVA with 
Bonferroni correction 
(p≤0.05) 
Randomized, sham-
controlled. Ten groups of 6 
mice were exposed to 0, 2, 4, 
6, or 8 minutes of a 10 Hz 
field either daily or every 
other day for 27 days and 
sacrificed for necropsy at day 
54. An additional 4 groups of 
4 mice at 0 and 8 min, daily 
and every other day, were 
treated for the same 27 days, 
but sacrificed at day 114 for 
necropsy. 
76 C57BL/6 
male mice 
Histological evidence of 
increased proliferation as 
well as differentiation and 
cell survival under certain 
exposure conditions. 
Treatment parameters of 
group 4M (2 min of exposure 
every other day) produced 
the optimal increase in 
oligodendrocyte proliferation 
and survival. These findings 
indicate the presence and 
activity of plasticity 
processes following 
electromagnetic field (EMF) 
exposure. No pathological 
findings were identified in 
the brain structures. 
BRQ-002-EF 
The Influence of 
Electromagnetic 
Exposure on 
Neurogenesis in 
Mice Following 
Traumatic Brain 
Injury 
Objectives: 
To assess the efficacy of ELF 
magnetic fields exposure in 
adult neurogenesis in mice after 
traumatic brain injury. 
Endpoints: 
Body weight (daily for first 
week, every other day for second 
week, weekly thereafter), 
Neurological severity score 
(NSS), morbidity and mortality 
(2x/day), histological analysis. 
When possible, scores 
were analyzed by two-
way ANOVA with 
Bonferroni correction 
(p≤0.05) 
Randomized, sham-
controlled. Mice were divided 
into 7 groups, including a 
control group. The groups 
varied in frequency exposure 
and duration of exposure (2 
min. or 8 min.). Two 
frequencies (7.86 Hz. And 10 
Hz.) and two timetables (once 
a day and once every other 
day) were evaluated. Animals 
in some subgroups were 
sacrificed at the end of the 
study, while others were 
subjected to continued 
observation. 
50 male 
C57BL/6 
mice 
No adverse events or 
abnormal changes in body 
weight were recorded in any 
study animals. Results 
indicate an effect of both the 
exposure frequency and 
exposure schedule in 
improving motor recovery in 
treated mice following TBI. 
Mice with daily exposure at 
7.86 Hz showed the greatest 
behavioral recovery. 
Additionally, no significant 
results were reported for the 
animals subjected to 
continued evaluation. 
BRQ-003-EF 
The Influence of 
Electromagnetic 
Exposure on 
Neurogenesis in 
Rat Stroke Model 
Objectives: 
To assess the efficacy of ELF 
magnetic fields exposure for 
enhancing neurogenesis in rat 
after stroke. 
Endpoints: 
Body weight, NSS, forelimb 
placement, object recognition, 
magnetic resonance imaging 
(MRI), Morbidity and mortality, 
histological analysis. 
When possible, scores 
were analyzed by two-
way ANOVA with 
Bonferroni correction 
(p≤0.05) 
Randomized, sham-
controlled. The 30 animals 
were divided 5 groups 
consisting of 6 animals per 
group, all of which were 
subject to transient middle 
cerebral artery occlusion 
(tMCAO) as a stroke model. 
EMF exposure was initiated 
on day 3 post stroke, and was 
administered for two minutes 
3x weekly, at 0 Hz, 3.93 Hz, 
7.86 Hz, 15.72 Hz, or 31.44 
Hz. 
30 male 
Sprague 
Dawley rats; 
transient 
middle 
cerebral 
artery 
occlusion 
(tMCAO) 
stroke model 
Consistent (but not 
significant) trend of higher 
behavioral scores in treated 
groups. Results varied with 
treatment parameters, with 
the best outcomes in the 3.93 
Hz group. MRI results were 
varied in the small measured 
sample (one representative 
from each group). In general, 
rats showed decreased 
perilesional edema after 
treatment as well as lateral 
ventricle widening. Upon 
histological analysis no 
pathological findings were 
identified. Other results 
suggested that the 
electromagnetic effect can 
induce neural regeneration 

 
 
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processes following a brain 
injury. 
BRQ-004-EF 
The Safety of 
Electromagnetic 
Exposure in 
Young and Aged 
Rats 
Objectives: 
evaluating the safety of ELF 
magnetic fields exposure in 
young and aged rats. 
Primary Endpoints: 
Morbidity and mortality, body 
weight, MRI, gross pathology, 
and histological analysis. 
When possible, scores 
were analyzed by two-
way ANOVA with 
Bonferroni correction 
(p≤0.05) 
Randomized, sham-
controlled. EMF exposures 
were performed from study 
day 1, three times a day 
(morning, noon and 
afternoon) until study day 14. 
Animals were exposed to 
EMF for 20 minutes each 
time using the same 
frequency (15.72 Hz.). 
22 male 
Sprague 
Dawley rats; 
11 in each 
group 
No adverse effect of EMF 
exposure was observed in 
either young or old animal 
groups. Higher T2 values 
indicated improved tissue 
integrity in brain regions that 
are normally subject to age-
related deterioration. 
Histological findings 
identified cell proliferation, 
indicative of plasticity, but 
with no distinct differences 
between groups. 
BRQ-005-EF 
The Influence of 
Electromagnetic 
Field Efficacy in 
Rat Model of 
Moderate Spinal 
Cord Injury – 
Hemi-crush 
Objectives: 
To assess the efficacy of ELF 
magnetic fields exposure on 
functional loco-motor recovery 
in adult rats following moderate 
spinal cord injury (hemi-crush). 
Primary Endpoints: 
Morbidity and mortality, body 
weight, clinical signs, Basso, 
Beattie, and Bresnahan 
locomotor test (BBB), grid 
walking test, Flexion reflex, 
MRI, gross pathology and 
histological analysis.  
When possible, scores 
were analyzed by two-
way ANOVA with 
Bonferroni correction 
(p≤0.05) 
Randomized, sham-
controlled. EMF exposures 
were performed from study 
day 1 – 30, for eight minutes 
a day, five times a week, for 
the control group (no 
treatment), and at 15.86 Hz or 
26.00 Hz for the treatment 
groups. From day 31 – 60, 
EMF exposure was for 20 
minutes a day, five days a 
week, at the specified 
frequency. 
28 male 
Sprague 
Dawley rats; 
T9 hemi-
crush 
Animal morbidity (including 
adverse clinical signs) and 
unscheduled death were 
observed in all groups and 
were attributed to the hemi-
crush model of spinal cord 
injury. No adverse events 
were recorded in animals that 
completed treatment.  
There was faster flexion 
reflex score (sensory 
function) improvement and 
more pronounced BBB loco-
motor functional score 
(motor function) 
improvement in both groups 
treated with EMF exposure 
compared to the control 
group. These effects were 
faster and more pronounced 
in the group treated with 
EMF exposure at 26.00 Hz. 
Fractional anisotropy (FA) 
and fiber reconstruction 
results indicate worsening of 
condition in control rat, and 
improvement of condition in 
treated rat. 
2.2.2 SUMMARY OF CLINICAL RESEARCH OF 
THE BQ 2.0 
Clinical investigations have been performed by BrainQ Technologies Ltd., in both stroke and 
spinal cord injury populations. In stroke patients, a pilot double-blind, parallel-group, 
randomized sham-controlled trial was performed (BQ3 trial) using the BQ 1.0 device, the direct 
predecessor of BQ 2.0. 
This trial was performed at the BLK Super Specialty Hospital, a multi-specialty hospital located 
in Delhi, India. The study was supervised by an international contract research organization 

 
 
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(CRO) and conducted in conformance with GCP and in accordance with the principles of the 
Declaration of Helsinki. Ethics Committee (EC) approval was obtained before the study 
initiation. All subjects provided written informed consent to participate in the study. 
The BQ3 trial enrolled patients diagnosed with a first ischemic stroke, with the diagnosis 
confirmed by imaging, and patients with a recurrent stroke in whom no previous neurological 
impairment in the same limb was reported before current stroke. Patients were recruited from 72 
hours to 15 days from stroke onset or 21 days from stroke onset, in case the patient was still 
unstable at day 15. To be considered eligible, patient’s FMA-UE had to be in the range of 10-45. 
This trial was designed for a population of 50 but was terminated just short of the pre-specified 
interim analysis (planned at n=26; discontinued at n=25, with EC approval) due to the outbreak 
of COVID-19. 
In total, 28 subjects were recruited to the study, of which 24 were randomized to receive either 
investigational (n=14) or sham therapy (n=10). Due to randomization error, which was revealed 
only post data lock and unblinding, two subjects received active treatment instead of sham 
treatment (n=16 and n=8, respectively). Of the 24 randomized subjects, 21 subjects completed all 
active (n=13) or sham (n=8) treatments (modified randomized as treated, mRT). To minimize 
bias, results of the mRT analysis are presented below (Figure 1). 
 
 
Figure 1. Breakdown of BQ3 trial population, as stipulated and as implemented 

 
 
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In addition to the hospital’s standard therapy regimen of 1-hour daily treatments, both study 
groups sat within the BQ device for the duration of each treatment session and received 10 
minutes of upper extremity PT/OT during the treatment session. The only difference between the 
investigational and sham treatment was whether or not the investigational device generated an 
EMF. Due to the non-invasive nature of the treatment, as well as the physical characteristic of 
the EMF, there was no noticeable difference between experimental conditions, and both subjects 
and operators were truly blinded. No significant differences between the baseline characteristics 
of the treatment and sham groups were identified. 
The first four subjects were considered run-in subjects and were assigned directly to the 
treatment group. Due to early termination of the study, the expectation for meaningful outcomes 
beyond mere positive trends was limited. Still, the significant results and positive trends obtained 
in multiple metrics presented below, establish an indication of the efficacy of the treatment under 
investigation in reducing global disability in the subacute phase of ischemic stroke. 
In a dichotomous analysis, where the percentage of subjects to reach little to no disability (mRS 
of 0-1) was compared to the percentage of subjects who remain with disability after treatment, 
the rate of non-disabled outcome (mRS 0-1) at final visit was 77% in the treatment group, versus 
only 25% of the sham-group subjects (P = 0.03). Furthermore, improvement by 2 or more mRS 
points occurred in 92% of subjects in the treatment group, compared to only 25% of the sham-
group subjects (P = 0.003). This was reflected in the shift analysis of mRS scores in treated 
versus control subjects (Figure 2). While the results for the sham group are comparable to other 
sham data from similar longitudinal studies, the treatment group substantially outperformed 
investigational devices from other studies, as will be further presented below. 

 
 
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Figure 2. BQ3 study – shift analysis of mRS scores 
In an mRS mean change analysis, the subjects in the treatment group experienced a mean change 
of 2.5 points, compared to 1.3 points in the sham group (P < 0.001). When comparing to peer-
reviewed publications and published datasets addressing populations comparable to that enrolled 
in the BQ3 study (baseline mRS of 3-4), the observational (48) and placebo (46, 47) groups 
perform similarly to BQ3 sham group (Figure 3). By derivation, despite the fact that the BQ3 
study enrolled a small number of subjects for statistically-significant conclusions to be drawn, 
the sham group performed as expected from historical data, while the treatment group 
substantially outperformed the control groups in the published evidence. 

 
 
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Figure 3. Modified Rankin Scale change in the treatment and control groups of the BQ3 study compared to historical control 
An mRS improvement of 2 or more points was observed in 92% of the treatment group subjects, 
while and improvement of 3 mRS points was found in 54% of the treatment group subjects.  
Only 25% of the sham group subjects improved by 2 points and a 3-point improvement was not 
reported in any of the subjects. Individual point shifts can be seen in  Figure 4 below.  
 
Figure 4. Parallel coordinates plot showing individual changes in mRS from sub-acute phase to 70 days post-stroke in the BQ3 study 
To better assess the magnitude of this kind of effect, the mean mRS difference between baseline 
and post-stroke day 90 mRS obtained with the BQ treatment was compared with its counterpart   
reported for all the currently recommended acute phase ischemic stroke therapies (Figure 5). 

 
 
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Figure 5. Observed mean difference effect in mRS at 90 days (treatment group – control/placebo group) post-stroke for different acute 
treatments, compared to the BQ treatment. 
The data presented are derived from Saver 2007 (62); thrombectomy data is reproduced from Goyal et al 2016 (16); data on Aspirin is 
based on a 4-level version of the mRS used in the International Stroke Trial (IST; (63)) and the Chinese Acute Stroke Trial (CAST; (64)), 
rather than the full 7-level mRS. 
Taken together, these findings indicate that the BQ therapy significantly decreases the degree of 
disability from baseline to final visit. The possibility of a treatment started within the subacute 
period yielding global improvement in ischemic stroke has the potential for clinically meaningful 
patient benefit that does not exist with standard of care treatments. 
Additional data and significant results from the above trial provide evidence that the reduction in 
disability achieved by BQ therapy is mediated partially by improvements in motor function, 
including upper and lower extremity function. In the BQ3 study, BQ therapy demonstrated 
improvement in several additional measures of motor function, including FMA-UE, FMA-LE, 
the Action Research Arm Test (ARAT), and BBT (Table 2). 
Table 2. BQ3 study – additional results for key endpoints 
Endpoint 
Timepoint 
Difference in mean change* 
P value 
FMA-UE 
Week 4 
13.6 
0.007 
FMA-UE 
Week 8 
8.4 
0.06 
ARAT 
Week 8 
9.6 
0.087 
ARAT-Pinch 
Week 8 
8.1 
0.008 
BBT 
Week 8 
14 
<0.0001 
FMA-LE 
Week 8 
3.9 
0.03 
NIHSS 
Week 8 
1.8 
0.03 
* Difference in mean change from baseline between treatment and sham groups 
In terms of safety, there were no device- or procedure-related adverse events (AEs) in this study. 
The reported AEs included a case of reported headaches and as rehospitalization due to a 
diagnosis of pancreatic cancer, all deemed unrelated to the device or the procedure.  

 
 
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2.3 
RISK/BENEFIT ASSESSMENT 
2.3.1 KNOWN POTENTIAL RISKS  
To date, there have been no device- or procedure related events in the clinical trials sponsored by 
BrainQ Technologies Ltd. 
The intensity of the BQ 2.0 is in the range of up to 1 Gauss, well below known safety thresholds, 
and the frequencies used are in the range of those normally observed in the human neural system 
(65). The device is similar in its field characteristics to pulsed electromagnetic field devices, 
including commercial home devices. These FDA approved or CE-marked devices use a similar 
or wider range of intensities and frequencies as the BQ 2.0. Examples of such devices are: 
Curatron-2000-HT (Curatronic Ltd., Jerusalem, Israel), indicated for treatment of acute and 
chronic pain as well as rheumatic disorders (mT range [mT = 10 G], frequency 1 –50 Hz), 
PhysioStim (Orthofix Medical Inc., Lewisville, TX, USA), indicated for treatment of nonunion 
fractures, and CervicalStim (Orthofix Medical Inc., Lewisville, TX, USA), indicated as an 
adjunct to cervical fusion surgery in patients at high-risk for non-fusion (1 Hz – 50 KHz, 2-G 
range), and IMRS (Swiss Bionic Solutions USA Inc., Cooper City, FL, USA), for energy and 
wellness (mT range, 0.5 –25 Hz). These and similar devices have been used and approved for 
many years (66-68). Furthermore, the BQ 2.0 intensity is significantly lower than approved 
stimulation devices, such as transcranial magnetic stimulation which often use fields of 1 – 1.5 T 
(10 000 – 15 000 G). An example of such a device is BrainsWay (BrainsWay, Jerusalem, Israel), 
FDA-cleared for a variety of psychiatric indications, and CE-marked for a variety of psychiatric 
and neurological treatments, including post-stroke rehabilitation. 
Potential risks have been identified during risk analysis which included assessment of risks 
related to the design of the device and evaluation of peer-reviewed clinical evidence on the state 
of the art in treatments involving or devices utilizing generation of electromagnetic fields.  
The following risks may occur during use of the device:  
− During the PT session 
o Fatigue during therapy; 
o Pain during therapy; 
o Fractures or abrasions (eg, cuts or bruises) sustained as a result of a fall during 
lower extremity PT exercises; 
− Transient neurological events due to exposure to electromagnetic fields 
o Paresthesia (tickling, numbing sensation in the skin); 
o Phosphenes (seeing light); 

 
 
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− Adverse tissue response or reaction (eg, sensitization, allergy, irritation, inflammation) to 
the material of a component of BQ 2.0.  
The following risks could occur due to guidance-discordant use of the device (ie, misuse16), 
including, but not limited to, in disregard of warnings in the IFU: 
− Fractures or abrasions (eg, cuts or bruises) sustained as a result of a fall after attempting 
to stand up while wearing the BQ 2.0; 
− Infection, cross-contamination due to lack of proper disinfection of the device between 
patients; 
The following events may occur due to device malfunction: 
− Discomfort or mild pain, headache, paresthesia, nausea and/or dizziness, or seizure due to 
malfunction of device and excessive electromagnetic emissions; 
- 
Interference with normal operation of active implanted medical device, such as 
pacemakers, due to malfunction of device and excessive electromagnetic emissions 
(subjects with implanted active electronic devices are excluded from this study); 
- 
Interference with magnetic-resonance (MR)–incompatible passive implants due to 
malfunction of device and excessive electromagnetic emissions (at a maximum of 7 G; 
Subjects with passive MR incompatible devices are excluded from this study). 
The following risks could occur due to a cyber-attack: 
– Tampering with the device and treatment parameters (eg, treatment intensity, frequency 
and duration). Tampering with the device could lead to higher intensity emissions. 
Subjects may experience side effects similar to those caused by stronger electromagnetic 
fields such as discomfort, headache, increased pain, paresthesia (numbness and tingling) 
and nausea or harm.  
– Tampering with the device may also lead to a lack of intended benefit.  
– Privacy breach, patient data or treatment data released. 
The following risks have occurred with electromagnetic devices at intensities higher by a factor 
of approximately 104:  
− Transient neurological events (rate of occurrence) 
 
16 per ISO 14971:2019 (definition 3.15): Use of a product or system in a way not intended by the manufacturer, but 
which can result from readily predictable human behavior. Readily predictable human behavior includes the 
behavior of all types of users, eg, lay and professional users. Reasonably foreseeable misuse can be intentional or 
unintentional. 
per ISO/TR 24971:2019: This includes use error (slip, lapse, or mistake), intentional acts of misuse, and intentional 
use of the medical device for other (medical) applications than intended by the manufacturer  

 
 
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o Mild pain or discomfort/headache (19.7%; (69)). 
o Dizziness (2.8%; (69)). 
o Seizure (<1%; (70)). 
o Nausea (reported in national registries). 
o Anxiety, depression, emotional changes, problems with sleep. There was a limited 
number of reports in national registries for these risks, and importantly to note 
that majority of the people who experienced these emotional changes had pre-
existing psychiatric conditions.  
o Transient cognitive changes were rarely reported. 
o Twitching was rarely reported.  
Burns may occur from overheating of or damage to electrical components in the device. 
For the exhaustive list of foreseeable adverse events and anticipated adverse device effects, 
together with their likely incidence, mitigation, or treatment, please refer to the IFU. 
For risk mitigation activities of the manufacturer, please refer to § 2.3.3. 
2.3.2 KNOWN POTENTIAL BENEFITS  
In post-acute stroke, improvement is expected to be incomplete using current standard treatment 
methods. The planned study hopes to provide patients with a safe and effective therapeutic 
means for the reduction of disability in adult patients with subacute ischemic stroke used in 
conjunction with physical and occupational therapy. 
The BQ 2.0 is designed to offer meaningful clinical benefit as demonstrated in several animal 
and human studies. The use of BQ 2.0 predecessor devices has provided data showing that the 
therapy helps restore physical function as well as reduce disability. BQ 2.0 treatment does not 
interfere with the standard of care a patient receives and can be used in conjunction with 
pharmacological and physical therapy treatment plans. 
In terms of compliance and ease of use, the BQ 2.0 device is non-invasive, patients can be 
treated in their own wheelchair (when applicable), with no observed pain or discomfort. Treated 
subjects report that there is no sensation at all associated with the activation of the EMF. 
The BQ 2.0 was designed to allow for remote (and specifically home) use from its inception; the 
need to provide meaningful in-home therapies has been significantly accelerated due to the 
outbreak of the COVID-19 pandemic. By enabling in home therapy, the Sponsor is able to 
reduce the risk for patients by way of avoiding clinic visits. The use of the BQ 2.0 is expected to 
benefit the patient and patient outcomes, with little or no increase in risk based on all clinical 
experience to date.  

 
 
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Based on the above, it is reasonable to assume that for the BQ 2.0, the expected benefits would 
outweigh the anticipated risks. 
2.3.3 ASSESSMENT OF POTENTIAL RISKS AND 
BENEFITS  
A risk analysis/assessment for the BQ 2.0 was performed according to ISO 14971. Potential 
hazards and their risks were reviewed. There are no special design features in BQ 2.0 that pose 
special safety concerns (eg, presence of medicinal, human, or animal components). Risk analysis 
focused on six main risk categories:  
− Energy, including hazards due to electrical safety, electromagnetic interference, 
electromagnetic emission, excessive temperature; 
− Biological and chemical, including hazards due to cross contamination and 
biocompatibility; 
− Operation, including hazards due to improper functionality of the device, wave generator 
malfunction, and improper functionality due to user errors; 
− Information, including hazards related to insufficient or confusing instructions for use 
− Cybersecurity, including potential hazards related to cybersecurity breach such as patient 
privacy breach, tampering with the application code and/or treatment parameters; 
− User errors. 
None of the residual risks, following mitigation, were found to be unacceptable and appropriate 
risk mitigations were implemented. 
By design, the BQ 2.0 minimizes safety risks to the subjects as far as possible by lacking sharp 
corners or edges and protecting the subjects from potentially hazardous contact with electrical 
components through use of:  
− Certified fire-retardant materials insulating relevant electrical components; 
As part of the BrainQ Technologies Ltd.’s risk mitigations: 
− The maximal field intensity at the applied frequencies is below the threshold for public 
exposure defined by the International Commission on Non-Ionizing Radiation Protection 
(71); 
− The electronics are limited in the energy that can be produced and, consequently, in the 
electromagnetic field intensity that can be generated, and are designed to maintain 
reliable functionality throughout the expected lifetime of the device; 

 
 
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− An internal ammeter measures current constantly during a treatment session to ensure 
values are as expected, so that treatment is halted if measurements fall out of the 
designated range; 
− An internal temperature sensor measures temperature constantly during treatment session, 
so that treatment is halted if measurements fall out of the designated range;  
− The generated field intensity decreases with distance in a negative proportion to the cube 
of the distance from the generating coil, thus, at a distance of 50 cm from the device the 
power of the generated field is negligible; 
− The device is limited by a physical fuse which ensures the device cannot surpass 15 W 
and reach higher, potentially dangerous, energy levels even in cases of system 
malfunction;  
− Even in cases of device malfunctions the field intensity cannot surpass 7 G;  
− The Qompass component Electronics are enclosed in a plastic frame (box) and separated 
from the user by a foam adhesive preventing direct contact with electronics. 
− The Qompass component Battery is certified in compliance with UN 38.3 testing 
standards. 
− The Qompass component uses off-the-shelf medical grade adhesive patches (e.g., 3M 
products), complying with ISO 10993 
− The operators (both at the clinic and at home) are required to undergo an approval 
process before operating the equipment; 
− The IFU contains instructions and warnings for the user to ensure appropriate use and to 
assist in case of malfunction. 
− The risk of falls is mitigated by the use of standard PT/OT exercises and assistance by an 
approved caregiver (please refer to § 6.1.2) or therapist depending on the subjects’ 
location. 
− To mitigate infection, cross-contamination, in this study the fabrics are replaced or 
disinfected between patients.  
− To mitigate and prevent a cybersecurity breach, all communication and entry points are 
secured (2 factor identification on all interactions between the application and server), no 
patient or treatment data is stored on the application, minimal non identifying data are 
stored on the cloud, and the company uses HIPPA complainant cloud and video 
conference platforms. 
In addition, the manufacturer has verified and validated through testing the: 
− Device performance in bench testing; 
− Device compliance with the basic electronic safety requirements per IEC 60601-1; 
− Device compliance with electromagnetic compatibility requirements per IEC 60601-1-2; 
− Device software functionality and reliability; 

 
 
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Safety of the BQ 2.0 use during pregnancy, breastfeeding, for individuals with a history of 
epilepsy or with implanted active electronic and passive MR incompatible devices has not been 
established, as consequently reflected in the eligibility criteria for this study. 
The manufacturer conducted a thorough risk evaluation and assessed the available clinical 
evidence on use of clinical use of electromagnetic fields, including use of ELF magnetic fields in 
patients with stroke. The manufacturer also assessed the pharmaceutical and interventional, 
OT/PT and other modalities available for treatment in the acute and subacute stages of stroke 
(reflected in §§ 2.1, 2.2, and 2.3.1). The manufacturer conducted several pre-clinical assessments 
(please refer to § 2.2.1) and a clinical trial with the previous model of the device (please refer to 
§ 2.2.2) in the intended population. Having done that, the manufacturer believes that the risks to 
which the study participants will be exposed do not exceed the risks associated with use of other 
solutions described thus far in peer-reviewed sources. Some issues cannot be addressed in a 
setting other than that of a clinical trial described in this clinical investigation protocol. These 
include providing an ultimate clinical confirmation of the efficacy of BQ 2.0 and lending further 
support to confirmation of its safety. 
Since this study, conducted as part of the clinical development of BQ 2.0, may support clearance 
of a device able to reduce disability in adult patients with subacute ischemic stroke, the benefit of 
this outcome outweighs the risks. 
3 
OBJECTIVES AND ENDPOINTS 
NOTE ON DEFINTIONS: For purposes of registration and reporting to clinical trials registries, 
in particular, ClinicalTrials.gov, the terms Primary Objectives and Endpoints as used in this 
section align with the terms Primary Purpose and Outcome Measures in ClinicalTrials.gov, 
respectively17. A description of the study objectives and endpoints is provided in a tabular form 
below. 
Objectives 
Endpoints 
Primary  
To show that the BQ therapy is effective in 
reducing global disability at 3 months post-
stroke in disabled patients with upper limb 
motor impairment when initiated 4 to 21 days 
following an ischemic stroke. 
Modified Rankin Scale (global disability) change from 
baseline (4-21 days post-stroke) to 90 days post-stroke. 
 
17 For purposes of registration on ClinicalTrials.gov, these are consistent with the definitions in 42 CFR Part 
11.10(a) and the provisions of the PHS Act § 402(j)(2)(A)(ii)(I)(cc) and §§ 402(j)(2)(A)(ii)(I)(ll), 402(j)(1)(A)(v), 
and 402(j)(3)(C)(ii) for Primary Purpose and Primary Outcome Measures, accordingly. 

 
 
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Secondary Efficacy  
To show that the BQ therapy is effective in 
reducing upper and lower limb impairment, and 
improving upper limb functionality, health-
related quality of life (HRQoL), and level of 
participation in instrumental activities of daily 
living (ADL) at 3 months post-stroke, when 
initiated 4 to 21 days following an ischemic 
stroke. 
The secondary efficacy endpoints will be analyzed in 
stepwise gatekeeper manner to control for multiplicity. 
The hierarchical order of analysis will be: 
1. Lead secondary endpoint: Fugl-Meyer Assessment 
for Upper Extremity (upper limb function) – change 
from baseline (4-21 days post-stroke) to 90 days 
post-stroke. 
2. Box and Block Test (arm motor function) – change 
from baseline (4-21 days post-stroke) to 90 days 
post-stroke. 
3. 10 Meter Walk Test (gait speed) – change from 
baseline (4-21 days post-stroke) to 90 days post-
stroke. 
4. Stroke Impact Scale Hand Domain (patient-reported 
hand function) – change from baseline (4-21 days 
post-stroke) to 90 days post-stroke. 
5. Stroke Impact Scale 16 (patient-reported physical 
functional limitation) – change from baseline (4-21 
days post-stroke) to 90 days post-stroke. 
6. 5-level EQ-5D (health-related quality of life) at 90 
days post-stroke. 

 
 
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Safety  
- 
To characterize the safety profile of the BQ 
therapy. 
- 
To show that the BQ 2.0 performs reliably. 
 
 
- 
Serious procedure or device related adverse events. 
- 
device deficiencies to detect operational reliability. 
 
Tertiary/Exploratory  
- 
To show that the BQ therapy is effective in 
reducing cognitive impairment, depression 
and fine-grained level of disability at 3 
months post-stroke, when initiated 4 to 21 
days following an ischemic stroke. 
- 
To characterize the long-term effect at 6 
months post-stroke of the BQ therapy 
effect on upper limb functionality and 
health-related quality of life (HRQoL).  
- 
To formally evaluate the cost-effectiveness 
of the BQ therapy over a lifetime horizon 
from the perspective of the United States 
healthcare system. 
- 
To explore the 
relationship between adherence to 
treatment as measured by the Qompass and 
clinical outcomes 
- 
Montreal Cognitive Assessment (global cognitive 
function) – at 90 days post-stroke. 
- 
Patient Health Questionnaire-8 (depression) – at 90 
days post-stroke. 
- 
Academic Medical Center Linear Disability Scale 
(granular level of disability) at 90 days post-stroke. 
- 
Modified Rankin Scale (global disability) change 
from baseline (4-21 days post-stroke) to 180 days 
post-stroke. 
- 
Stroke Impact Scale Hand Domain (patient-
reported hand function) – change from baseline (4-
21 days post-stroke) to 180 days post-stroke. 
- 
5-level EQ-5D (health-related quality of life) at 
180 days post-stroke. 
- 
Formal cost-effectiveness analysis over a lifetime 
horizon from the perspective of the United States 
healthcare system. 
- 
Relationship between adherence to treatment as 
measured by the Qompass and the clinical 
outcomes 
4 
STUDY DESIGN  
4.1 
OVERALL DESIGN 
− Type of trial: prospective, multicenter, double-blind, randomized, sham-controlled, 
parallel two-arm study following a sample-size–adaptive design with a single planned 
interim analysis (for details of the interim analysis, please refer to § 9.4.6). 
− Statement of hypothesis: improvement in mRS score from baseline to 90 days post-stroke 
will be greater in patients allocated to active stimulation (BQ 2.0 group) than in patients 
allocated to sham stimulation (sham) group. 

 
 
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− Sample size and allocation: 150 subjects18 assigned at 1:1 allocation ratio to either active 
or sham group. 
− Study population: ischemic stroke subjects with upper limb motor impairment. 
− Phase: pivotal. 
− Number of sites: approximately 20 centers. 
− Total enrollment from each site to be no more than 20% of the total sample size. 
− Duration for each subject: participation in this study will start at day 3-21 post-stroke and 
will last up to 180 ± 15 days post-stroke. 
NOTE: Sponsor’s representative(s) may be present during study interventions, in-person or via 
combined audio and video remote conferencing or audio only, if video is not available. Presence 
of the Sponsor during procedures is for observational purposes only and is predicated on the 
premise of benefit to subject’s well-being, as exemplified in the Guidelines on Good Clinical 
Practice specific to Advanced Therapy Medicinal Products (ATMP) issued by the European 
Commission  https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-
10/atmp_guidelines_en.pdf. 
Despite of its non-binding nature, EU-only application, and non-universal scope, it shows that 
there are conditions where subject’s well-being may benefit from Sponsor’s presence and this 
would not be considered unethical. 
According to this guidance, “The presence of the sponsor (or a representative thereof) during the 
administration of the ATMP to the clinical trial subject or in any upstream collection procedure 
is only acceptable if it is duly justified. If such presence is envisaged before the start of the 
clinical trial, this should be explained in the informed consent. If, exceptionally, the presence of 
the sponsor (or a representative thereof) has not been foreseen from the outset of the clinical 
trial but it is justified for reasons related to the protection of the clinical trial subjects or to 
detect and prevent errors in the extraction of cells/tissues and/or administration, the clinical trial 
subject should be informed a posteriori. As appropriate and in connection with the enrolment of 
future patients, the sponsor should submit an amendment to the protocol and an update to the 
informed consent.” 
Consequently, the fact of possible presence of the Sponsor’s representative(s) during the study 
treatment, to the extent permissible by local laws and regulations, will be described in the 
informed consent process and detailed in the informed consent documentation, at all sites 
participating in this study. 
 
18 May also be referred to as study participants or simply participants in this protocol. 

 
 
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4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
The randomized, double-blind, sham-controlled, trial design has been selected as it is the most 
rigorous to employ in device trials. Randomization best assures balance between treatment 
groups in both measured and unmeasured baseline variables. Sham-controlled blinding prevents 
both patient and rater bias in outcome assessment (72). 
Start of study treatment 4-21 days after index stroke allows initiation during the time period of 
maximal neural reorganization following stroke, as well as assures that patients are medically 
and neurologically stable at time of entry and are in a well-controlled environment during initial 
stimulation sessions.  
Enrolling patients with moderate-severe disability at baseline assures patients have substantial 
potential for improvement, minimizing ceiling effects. Patients with upper extremity motor 
deficits are selected because upper limb motor impairment is a major cause of disability in 
ischemic stroke patients and upper extremity therapy exercises are performed comfortably by 
patients when seated within the device.  
The modified Rankin Scale was selected as the primary endpoint because it is a measure of 
global disability and all level changes from 0 to 5/6 are known to be of unequivocal and of 
substantial value to patients and clinicians. The choice of the Fugl-Meyer Assessment for Upper 
Extremity as the lead secondary endpoint adds a focused evaluation of the leading target for 
improvement – upper limb function. 
4.3 
JUSTIFICATION FOR DOSE 
Not applicable. 
4.4 
END OF STUDY DEFINITION 
A participant is considered to have completed the study if he or she has completed all phases of 
the study including the last visit or the last scheduled procedure shown in the Schedule of 
Activities (SoA; § 1.3). The end of the study is defined as completion of the last visit shown in 
the SoA for the last subject in the trial19. 
 
19 42 CFR Part 11 § 11.10(a)(3) “study completion date”; ISO 14155:2020 § 8.1 

 
 
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The study primary completion date,20 is the date that the final subject was examined or received 
an intervention for the purposes of final collection of data for the primary 90 days outcome, 
whether the trial concluded according to this protocol or was terminated. 
For the purposes of regulatory submissions to support market approval, data through 90 days is 
intended to support safety and effectiveness and submission is planned when the last subject 
enrolled is through the 90-day study period. Additional longer-term data is exploratory in nature. 
 
5 
STUDY POPULATION 
5.1 
INCLUSION CRITERIA 
In order to be eligible to participate in this study, an individual must meet all of the following 
criteria: 
1. mRS score of 3 or 4. 
2. FMA-UE score between 10-45 (inclusive) of impaired limb. 
3. Age 22 to 85 years of age (inclusive). 
4. Diagnosed with an ischemic stroke, confirmed by CT21 or MRI22 imaging. 
5. Four to 21 days from stroke onset (or last known well). 
6. Pre-stroke mRS of 0 or 1. 
7. Able to sit with the investigational device for 40 consecutive minutes, in the opinion of 
the investigator or designee. 
8. Can follow a 3-step command, such as “take the paper, fold it in half, and return it to 
me”. 
9. Willingness to participate in occupational/physical therapy activities during study 
intervention sessions. 
10. Availability of a relative or other caregiver able to assist during PT/OT treatment, and to 
operate an application installed on a mobile device, including a video call.  
11. If female, not pregnant (as confirmed by a urine or a blood test, or as determined by an 
official medical document) or breastfeeding and with no ability to become pregnant or on 
an acceptable method of contraception during the study 
12. Informed consent signed by subject (if competent) or legally authorized representative. 
 
20 42 CFR Part 11 § 11.10(a)(3) “completion date” or “primary completion date” synonymous to the “completion 
date” defined in section 402(j)(1)(A)(v) of the Public Health Service Act [42 U.S.C § 282(j)(1)(A)(v)] 
21 Computed tomography 
22 Magnetic resonance imaging 

 
 
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5.2 
EXCLUSION CRITERIA 
An individual who meets any of the following criteria will be excluded from participation in this 
study: 
1. Severe neglect impairment (NIHSS item 11, score = 2) or neglect that is severe enough to 
interfere with reasonable performance of study procedures.  
2. Implanted active electronic or passive MR-incompatible devices. 
3. Previous ischemic or hemorrhagic stroke within 2 weeks before the index stroke. 
4. Pre-existing neurological condition (eg, Alzheimer’s disease, Parkinson’s disease, 
multiple sclerosis, traumatic brain injury, spinal cord injury) or physical limitation that 
would interfere significantly with the subject’s participation in the study and/or confound 
neurological or functional evaluation. 
5. Active epilepsy or currently taking anti-epileptic medication (indicated for the treatment 
of a seizure disorder), or seizure in the last 5 years 
6. Significant visual disturbances that cannot be corrected and that would interfere 
significantly with the subject’s participation in the study and/or confound neurological or 
functional evaluation. 
7. Unstable serious illness/condition (eg, active cancer, severe heart failure, active 
psychiatric condition) or life expectancy of less than 12 months. 
8. A known severe allergic reaction to acrylic-based adhesives.  
9. Ongoing alcohol abuse and/or illicit drug use. 
10. Participation in another trial that would conflict with the current study or clinical 
endpoint interference may occur. 
11. Employee of the Sponsor. 
12. Prisoner. 
5.3 
LIFESTYLE CONSIDERATIONS 
Not applicable. 
5.4 
SCREEN FAILURES 
NOTE ON POINT OF ENROLLMENT:  
1. Screening Phase:  
a. Subjects who consented to participate in the initial study assessments for 
eligibility will be considered enrolled in the Screening Phase. 
b. As long as done within 4 to 21 days from stroke onset, subjects may be reassessed 
for eligibility before being deemed screening failure. 

 
 
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c. Any subject who consented but was not randomized for any reason will be 
deemed a screening failure. Such subject will not be counted towards the planned 
study sample size. 
2. Randomized Phase:  
a. Subjects who had their eligibility criteria verified and were randomized will be 
considered enrolled. 
A minimal set of screen failure information is required to ensure transparent reporting of screen 
failure participants, to meet the Consolidated Standards of Reporting Trials (CONSORT) 
publishing requirements and to respond to queries from regulatory authorities. Minimal 
information includes demography, screen failure details, eligibility criteria, and any adverse 
event and serious adverse event (SAE). 
All participating sites, including ACHs and IRFs, will maintain a screening log that will consist 
of all consented subjects who were or were not randomized. For each screen failure subject, the 
log will include: date of consent; informed consent version and language; date of screen failure; 
and reason(s) for exclusion from the treatment phase of the trial. 
Screening log containing details of screen failures, including reasons for such, will be kept in the 
Investigator Site File (ISF). 
5.5 
STRATEGIES FOR RECRUITMENT AND RETENTION 
Recruitment  
Publicly available or advertised information:  
The trial listing on ClinicalTrials.gov will be publicly accessible to patients and families.  
− The Sponsor’s website may inform site visitors of the study on the webpage listing past, 
current, and future studies. 
− A study specific website may inform site visitors of the study and its key 
characteristics.23   
− The Sponsor’s social media accounts may contain a link to the corresponding entry(ies) 
in the publicly accessible database(s) described above in this section. Social networks 
may be used to advertise the trial. 
− Direct advertising may include newspaper/radio/TV/bulletin boards ads.  
− Posters and/or flyers may also be issued to advertise the trial.  
 
23 www.emagine.care  

 
 
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The advertising activities in the indented list above will only commence following 
documented approval of IRB of such material. 
Optimization of recruitment procedures: 
NOTE: The strategies listed below will be implemented unless agreed otherwise with the 
participating site in a site-specific manual of procedures (MOP).   
- 
Participating Acute Care Hospitals (ACH) 
o Recruitment may begin in the ACH, to ensure identification of all potentially 
eligible patients, facilitate access to the brain CT and MRI scans performed at the 
acute care hospital, and to give subjects and families maximal time to reflect on 
the trial before proceeding to the randomization phase. 
o Study Coordinators at the participating ACH, together with stroke team 
physicians and discharge planners, will each workday review patients newly 
planned for discharge to a participating IRF, SNF, outpatient, or to a home 
setting. Patients identified as potentially eligible based on age and time from 
index stroke will be approached for study consideration. 
- 
Inpatient Rehabilitation Facilities (IRF) 
o Evaluate subjects consented in a participating ACH for continued study eligibility 
and progression to the randomization phase 
o Identify, consent and enroll patients admitted from both participating and non-
participating ACH 
o Study Coordinators at the IRF will each workday review with rehabilitation 
physicians and nurses newly admitted ischemic stroke patients. Patients identified 
as potentially eligible based on age and time from index stroke will be approached 
for study consideration.  
Additional sites may be evaluated in case of slow enrollment or lack of the investigation site 
compliance with this protocol, GCP, or applicable regulations. 
Retention 
Strategies to optimize subject retention will include:  
− Study staff will make subjects and families feel listened to, valued, and supported 
throughout by listening to subject/family sentiment (and acting on it). 
− After discharge from inpatient facility, further study visits will generally be conducted in 
the subject’s home, to avoid the inconvenience and expense of patient travel to a study 
site. 

 
 
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− Phone calls, emails, video calls, and/or text message reminders about upcoming 
appointments may be used to help increase visit attendance and overall trial retention. 
Vulnerable subjects 
Vulnerable subjects (include, but are not limited to pregnant women, those who lack consent 
capacity, including the mentally ill, cognitively impaired, children (see note below in this 
section), employees of the Sponsor, or prisoners [even if a participant becomes a prisoner during 
the study, in which case his/her participation in the study will be terminated]) will not be 
enrolled in this study. The only exception may be made for the possibility of enrollment of 
employees of the sites (the latter will be reflected in the informed consent form). Analogously, 
patients lacking consent capacity due to emergency situations24 will not be included. 
NOTE ON THE DEFINITION OF “CHILDREN” 
The U.S. 21 CFR 56.111 refers to children, prisoners, pregnant women, handicapped, or 
mentally disabled persons, or economically or educationally disadvantaged persons as vulnerable 
populations. Children are defined in 21 CFR 50.3(o) and 45 CFR 46.402(a) as persons who have 
not attained the legal age for consent to treatments or procedures involved in clinical 
investigations, under the applicable law of the jurisdiction in which the clinical investigation will 
be conducted25. However, the age of legal competence differs across jurisdictions (73). 
The statute in 21 U.S.C. § 360j(m)(6)(E)(i) and (ii) (incorporating Section 520m(6)E(i) and (ii) 
of the Federal Food, Drug, and Cosmetic Act [FD&C] Act) defines pediatric patients as age 21 
years or younger at the time of diagnosis or treatment and specifies categories of pediatric 
subpopulations. Further, 21 U.S.C. § 360e-1(a) (Section 515A of the FD&C Act), which requires 
sponsors of premarket application (PMA) and humanitarian device exemption (HDE) 
applications and supplements to submit information on pediatric subpopulations and pediatric 
patients, uses the same definition of “pediatric subpopulations”. Accordingly, for medical device, 
the U.S. FDA interprets the statutory definition of pediatrics as individuals who are 21 years of 
age or younger. 
Consequently, to account for any territory-specific variations in definitions, this study will only 
enroll subjects who are at least 22 years of age. 
For detailed recruitment and retention plan, please refer to the MOP. 
 
24 For instance, as described in Article 68 of the MDR 
25 45 CFR Subparts B, C, and D defines vulnerable populations as patients who are racial or ethnic minorities, 
children, elderly, socioeconomically disadvantaged, underinsured 

 
 
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6 
STUDY INTERVENTION 
6.1 
STUDY INTERVENTION(S) ADMINISTRATION 
6.1.1 STUDY INTERVENTION DESCRIPTION 
The BQ 2.0 (Figure 6) is a medical device that produces and delivers non-invasive, extremely low 
intensity and frequency (1-100 Hz.; up to 1 G), frequency tuned electromagnetic fields in order to 
stimulate neuronal networks with the aim of reducing disability and promoting neurorecovery. The 
technology behind the device technology utilized explanatory machine learning (ML) and Brain-
Computer Interface (BCI) tools to identify high-resolution spectral patterns that characterize motor 
functions; the tools are based on a large database of EEG spectra taken during functional motor tasks. 
These spectral patterns are then translated into a frequency-tuned, low-intensity and non-invasive 
electromagnetic field treatment, which applies similar patterns directly to the patient’s CNS. 
 
The BQ 2.0 is intended to be used in conjunction with the current standard of care. Treatment 
with BQ 2.0 includes 45 sessions of 60 minutes. Each session includes 40 minutes of exposure to 
the BQ therapy. Throughout the session, subjects will be asked to perform a standardized device-
guided exercises to further support their recovery process. These exercises will be based on a 
pre-defined and evidence-based physical and occupational therapy regimen focused on upper and 
lower extremity rehabilitation, aligned with the Class 1 level A recommendation for patients with 
stroke to participate in a home-based rehabilitation program. 
From a user perspective, the BQ 2.0 is a portable, non-invasive treatment designed to be used in a 
variety of settings (eg, in a clinical facility or patient’s home).  
6.1.1.1 DEVICE SIZE(S) 
For device dimensions, please refer to the IFU. 
6.1.1.2 DEVICE MODEL(S) 
• The BQ 2.0. includes three configurations which vary in size to accommodate different 
individuals based on their physical characteristics. 

 
 
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6.1.1.3 DESCRIPTION OF EACH COMPONENT 
To achieve its purpose, BQ 2.0 (Figure 6) comprises the DEVICE and the SOFTWARE APPLICATION 
installed on ANDROID based TABLET: 
1. DEVICE (Figure 7) – Wearable Device which includes: (1) embedded magnetic coils; (2) 
Waveform generator; (3) Rechargeable battery; and (4) the Qompass. The magnetic COILS 
are configured in three-dimensional shapes; with one COIL in the shape of a rectangle that 
goes along the spine, and two circle-shaped COILS that surround the brain.  
Custom plastic COMBS are used to ensure correct placement of the COILS. These are 
secured to a sheet of polypropylene. Also secured to the polypropylene are a custom box 
containing the printed circuit board which creates the wave function and a custom 
BATTERY BOX containing the battery to power the Device. The entire structure is covered in 
a layer of fabric which includes a WAISTBAND and SHOULDER STRAPS to secure the Device 
to the patient. THE QOMPASS (Figure 8) is a single-use sensor designed to be placed on the 
subject’s forehead for the duration of each treatment session via an adhesive. It contains 
sensors that detect the electromagnetic field that the subject is exposed to, to ensure a 
subject receives the treatment as intended and allow for in depth monitoring and 
treatment optimization26. Each unit is designed for one-time use to simplify the user 
experience. 
Control of operation of the DEVICE is enabled through operation of the 
2. SOFTWARE APPLICATION v. 5.0 and above (Figure 9) – (Android; Transmission Control 
Protocol/Internet Protocol (TCP/IP) communication), installed on an Android-based 
mobile device. The SOFTWARE APPLICATION controls the functionality of the DEVICE. Data 
collected is uploaded to a cloud compliant with the Health Insurance Portability and 
Accountability Act (HIPAA; implemented in 45 CFR Part 160 and Part 164, Subparts A 
and C) and the General Data Protection Regulation (GDPR; Regulation (EU) 2016/679). 
Data upload is performed strictly for backup purposes. No data interpretation is 
conducted on the cloud. 
The SOFTWARE APPLICATION does not require entry of any patient-identifying information into 
the device, nor connecting the device to hospital data systems, eg, electronic medical 
record (EMR). To use the device, a system administrator must create an account for each 
user to login (Figure 9). Existing patients can be selected from the patient selection 
screen by authorized caregivers or operators (Figure 10). Overview of the upcoming 
treatment is then presented (Figure 11). Treatment screen is presented following 
treatment initiation (Figure 12). 
 
26 In the clinical trial setting the data will only be collected, will not be accessible to blinded personnel or 
participants and will not be used to actively monitor and optimize the dosage in order to maintain the blinding. 

 
 
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For the exhaustive description and operational instructions of BQ 2.0, please refer to the IFU. 
 
Figure 6. BQ 2.0 – overview 

 
 
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Figure 7. BQ 2.0 – DEVICE components 
Figure 8. The Qompass 

 
 
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Figure 9. BQ 2.0 SOFTWARE APPLICATION sign in screen 

 
 
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Figure 10. BQ 2.0 SOFTWARE APPLICATION patient selection screen 

 
 
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Figure 11. BQ 2.0 SOFTWARE APPLICATION treatment overview screen 

 
 
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Figure 12. BQ 2.0 SOFTWARE APPLICATION treatment screen 
6.1.1.4 DURATION OF EXPOSURE 
The maximal exposure to BQ 2.0 stimulation during a treatment session is 40 consecutive 
minutes. 
6.1.1.5 FREQUENCY OF EXPOSURE 
The BQ 2.0 will be used 5 times a week to a total of 45 treatment sessions in each subject. 
6.1.1.6 SUMMARY/REPORT OF TEST VALIDATION STUDIES 
For summary of test validation studies please refer to the IFU. 
6.1.2 DOSING AND ADMINISTRATION 
Randomized patients will receive active or sham study intervention sessions using BQ 2.0 (active 
or sham therapy, respectively), starting 4-21 days after stroke onset and no later than 2 days after 
randomization. Sessions will be conducted 5 times a week. Each session will last up to 60 
minutes, with active or sham field being turned on for up to 40 minutes. The only difference 
between the BQ 2.0 active stimulation and sham therapy is that the sham device does not 
generate electromagnetic fields during treatment. Subjects in both the active intervention group 

 
 
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(BQ 2.0 group) and sham group will be asked to perform trial-specified physical and 
occupational therapy activities during each session, in addition to their standard care 
rehabilitation therapies. 
During the study, 45 sessions of active or sham therapy will be conducted in either inpatient, 
outpatient or home setting.  
. A trained member of the site study team (the “Clinic Operator”) will be responsible for 
training and approving the subject’s caregiver  to operate the session independently.  
Before an approval to operate a session independently (the “Approval”) is granted by the Clinic 
Operator, a Clinic Operator will train the caregiver and supervise the sessions, either in-person or 
remotely. Once an Approval was granted, sessions will be conducted with the assistance of a 
caregiver while the Clinic Operator will provide periodic oversight (combined audio and video 
remote conferencing or audio only, if video is not available). If needed, and at their discretion, 
the Clinic Operator may join sessions following the Approval too. 
A complete session is one which includes at least 40 minutes of stimulation. For each treatment 
session, after the initiation of the stimulation, a pause in or early cessation of stimulation after the 
initiation of the stimulation, should be avoided as much as possible.  If the stimulation is paused, 
the session may be reinitiated within 30 minutes. Additional pause before the stimulation is 
complete (or before 30 minutes of stimulation have been complete in the first 5 occurrences) will 
result in session termination. If over 30 minutes of stimulation have been completed but the 
stimulation was stopped before completion, in the first 5 occurrences – the session will be 
considered complete. Subsequent shortened sessions will be considered incomplete. Missed or 
incomplete treatment sessions will be rescheduled until 45 treatment sessions are completed. 
Rescheduled sessions will not result in having over 5 treatment sessions administered in a week. 
Instead, this will extend the total number of weeks required to complete 45 sessions. Treatment 
sessions can be completed until the day before the Day 90 follow-up visit. Missed treatments 
won’t be considered as Protocol Deviation as long as rescheduled and completed within the 
allowed window (until the day before the 90 Day (±15) follow up visit). 
For treatment schedule disruptions that will lead to subject withdrawal from the study, please 
refer to § 7.2.  
6.1.3 CONTROL INTERVENTION DESCRIPTION 
Sham intervention is identical to BQ 2.0 therapy, except that no electromagnetic energy is 
generated by BQ 2.0. Other than that, all provisions of § 6.1.1 apply here as well. 

 
 
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6.2 
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY 
6.2.1 ACQUISITION AND ACCOUNTABILITY 
Investigators will administer study device only to subjects included in this study and following 
the procedures set out in this protocol. All study devices must be accounted for throughout the 
study using accountability logs. Investigators must maintain accurate and adequate records, 
including dates, serial number, quantities received (if applicable), expiry date, inventory, and 
individual usage. These records will be verified by the study Monitors during site visits. 
For information on procedures and particular materials (eg, packaging materials) and instructions 
for the safe return of investigational devices, including those that are potentially hazardous, 
please refer to the study MOP. 
6.2.2 FORMULATION, APPEARANCE, 
PACKAGING, AND LABELING 
Please refer to the IFU for detailed descriptions. 
6.2.2.1 STUDY DEVICE 
The BQ 2.0 (active and sham), as provided by the Sponsor for this study, comprises a single 
package including the DEVICE, BQ 2.0, and its accessories, including the SOFTWARE APPLICATION 
installed on an Android-based mobile device and approximately 50 units of the QOMPASS, 
packaged and transported in a custom-made packaging. The packaging is made of fabric and 
mounted to a wheel system to allow for carrying by hand or wheeling of the device. The 
packaging includes custom bags and compartment for the BQ 2.0 accessories. Foam padding in 
the BQ 2.0 packaging maintains the device structure and protects it from damage.  
6.2.3 PRODUCT STORAGE AND STABILITY 
BQ 2.0 shall be stored in designated packaging in accordance with the requirements specified in 
the IB. 
6.2.4 PREPARATION AND HANDLING 
Each BQ 2.0 device will be tested prior to allocation to a study participant.  
Upon the completion of all study treatments, in coordination with the site and the study 
participant, the BQ 2.0 shall be collected and sent to a location designated by the Sponsor or to 

 
 
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the site, for cleaning and refurbishment as described below. A designated Sponsor’s 
representative or study team member will complete the following tasks:  
1. Replace all fabrics which can come in contact with an individual to avoid cross 
contamination 
2. Inspect the device thoroughly to ensure all of the components are intact and do 
not have any visual damage  
3. Reset the SW application to allow for a new user to use the application with 
his/her credentials 
4. Test the entire set up by performing a treatment session simulation 
For complete product cleaning instructions please refer to the MOP. 
 
Only upon the successful completion of all refurbishment and cleaning tasks shall the device be 
deemed suitable for reuse on a future study participant.  
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
6.3.1 ALLOCATION TO STUDY INTERVENTION 
After informed consent has been elicited from the subject or his/her legally authorized 
represented, and the subject is determined to fully meet the study eligibility criteria, he/she will 
be equally allocated (with a 1:1 ratio) to one of the following 2 treatment groups based on a 
permuted block randomization scheme with blocks stratified by site, age (22-69, 70-85) and 
mRS score at baseline (3 vs 4): 
− BQ 2.0 active stimulation group  
− BQ 2.0 sham stimulation group  
Allocation (randomization) of participants to study groups will proceed through the use of the 
EDC system (Syncrony) for randomization and the BQ 2.0 Administrator Panel for treatment 
allocation. The site personnel (Study Coordinator or specified designee) will be required to enter 
or select information including but not limited to the user’s ID and password, the protocol 
number, and the participant number. The site personnel will then be provided with a group 
assignment and randomization number. The Syncrony system will provide to the unblinded site 
personnel the study intervention allocation assigned. The randomization schedule and treatment 
arm assignments will be kept by Syntactx-NAMSA data manager with appropriate security 
measures and access control. 
6.3.2 BLINDING OF SITE PERSONNEL AND 
SUBJECTS 

 
 
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This is a double-blind study, subjects and Investigators will be blinded to the device setting 
(Active/Sham). The study site team members receiving, storing, dispensing, preparing, and 
administering the study interventions will be blinded. Subjects’ caregivers will also be blinded. 
There are no differences in the active and sham device appearance. Due to the non-invasive 
nature of the treatment, as well as the physical characteristic of the EMF, there is no noticeable 
difference between sessions conducted using an active or a sham device, facilitating full blinding 
of both subjects and Investigators. 
BQ 2.0 does not produce any noticeable sound, light or sensation in connection with the 
stimulation which may disclose the arm assignment, making it ideal for testing in a sham-
controlled setup. During sham treatment sessions, for purposes of maintaining the blind, the 
device will function as if it is delivering the therapy (i.e., the device will turn on and all 
indicators will function), but the frequency and intensity parameters that are not visible to the 
subject or site study members will be set to zero so that no stimulation is delivered. Furthermore, 
in the clinical trial setting, the data collected via the Qompass component of the device will not 
be accessible to blinded personnel or participants or used to actively monitor or optimize the 
dosage in order to maintain the blinding.  
An authorized un-blinded individual at the site will be the only person to receive the group 
assignment of the randomized subject, and will enter the subject’s group assignment to the study 
device, in accordance with the IFU and/or training received from the Sponsor. For more 
information, please refer to the Blinding Plan. 
6.3.3 BLINDING OF THE SPONSOR 
The Sponsor, the sites and the study statistician will remain blinded throughout the study. This 
blinding will include the interim analysis results as well; only the decision made will be shared. 
An independent unblinded statistician (not the study statistician) will perform the assessments for 
the interim analysis. An unblinded representative of the Sponsor may be designated as well. 
For unblinding procedures in place for the planned interim data analysis, please refer to § 9.4.6. 
as well as to the Unblinding Plan. 
6.3.4 BREAKING THE BLIND 
The randomization schedule and treatment arm assignments will be kept by Syntactx-NAMSA 
data manager with appropriate security measures and access control. In case of an emergency, 
the Investigator has the sole responsibility for determining if unblinding of a subject’s study 
intervention assignment is warranted. Subject safety must always be the first consideration in 
making such a determination. If the Investigator decides that unblinding is warranted, the 

 
 
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Investigator should make every effort to contact the Sponsor prior to unblinding a subject’s 
group assignment, unless this could delay further management of the subject. If a subject’s group 
assignment is unblinded, the Sponsor must be notified within 24 hours after breaking the blind. 
The date and reason that the blind was broken must be recorded in the source documentation and 
communicated to the sponsor in a formal communication medium. 
6.4 
STUDY INTERVENTION COMPLIANCE 
Following intervention, appropriate CRF must be filled in, within the time frame for completion 
as specified in Table 5. The date and time of each treatment administered will be recorded in the 
source documents and recorded in the CRF. The study Monitor will check the CRF against the 
accountability log and related treatment session worksheets used by the site to verify the number 
of devices dispensed on a per-subject basis. 
6.5 
CONCOMITANT THERAPY 
All sites will provide concomitant medical therapies to prevent recurrent stroke and conventional 
rehabilitation therapy to maximize recovery from the index stroke according to United States 
national guidelines (43, 74, 75). 
All concomitant prescription medications, over-the-counter medications, and supplement 
medications taken during study participation will be recorded on the appropriate CRFs. For this 
protocol, a prescription medication is defined as a medication that can be prescribed only by a 
properly authorized/licensed clinician.  
6.5.1 RESCUE MEDICINE 
Not applicable. 

 
 
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7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1 
DISCONTINUATION OF STUDY INTERVENTION 
Any symptoms of treatment-emergent clinical deterioration in subject’s condition requiring 
intervention of the medical team to alleviate these symptoms and qualifying for toxicity Grade 3 
(or higher) on the CTCAE v.5.0 scale will result in a halt of administration of the study 
intervention for that treatment session; halting for a longer period of time will occur only if 
deemed necessary by the Investigator. 
In general, discontinuation of administration of the study intervention, for any reason, does not 
mean discontinuation from the study, and the remaining study procedures should be completed 
as indicated by the study protocol, unless informed consent is withdrawn. If a clinically 
significant finding is identified (including, but not limited to changes from baseline) after 
enrollment, the Investigator or qualified designee will determine if any change in subject 
management is needed. Any new clinically relevant finding will be reported as an AE. For 
requirements on reporting of adverse events, serious adverse events and unanticipated problems 
please refer to §§ 8.3.5, 8.3.6, and 8.4.2, respectively. 
The data to be collected at the time of discontinuation of administration of the study intervention 
will include the date and reason for discontinuation and any data on the adverse event(s), if 
applicable. 
Women who become pregnant during the trial will continue to be assessed, including assessment 
of pregnancy outcomes, and investigational device administration will be discontinued. Further 
provisions on reporting of pregnancy, including period of reporting are in § 8.3.9. 
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
Participants are free to withdraw from participation in the study or discontinue the study 
intervention at any time upon request. Those wishing to discontinue participation do not have to 
provide a reason; however, when appropriate, the site investigator should discuss the study, 
informed consent, and any on-going risks and benefits to continued participation with the 
participant. 
In addition to discontinuation of administration of the study intervention (section 7.1), subject 
participation in the study may be terminated by the Investigator or the Sponsor if any one or 
more of the following conditions are met: 
− occurrence of an unexpected serious adverse event; 

 
 
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− pregnancy; 
− loss to follow-up (refer to § 7.3 for accompanying instructions); health conditions that 
require treatment that might affect the procedure and/or its outcome; 
− significant protocol deviation (please refer to § 10.1.10) or noncompliance, either on the 
part of the subject or Investigator. These will include (but not limited to): 
o enrollment in violation of the study eligibility criteria; 
o performing the trial procedure not as prescribed in the BQ 2.0 IFU; 
o other ethical or clinical considerations at the discretion of Investigator. 
o enrollment in another interventional study overlapping with the period of 
participation in this study. 
Data collected prior to withdrawal of consent will remain in the study database, but no further 
data will be collected on those who withdraw. Follow up on serious adverse events that are not 
resolved by the time that the subject leaves the study will be handled as defined in § 8.3.4. 
Follow up on pregnancy outcome will be handled as defined in § 8.3.9. 
Withdrawn/discontinued randomized subjects will not be replaced. 
If a subject withdraws from the clinical investigation, the reason(s) shall be recorded. 
Withdrawals will be recorded, analyzed, and reported to local IRBs/ECs as required. 
7.3 
LOST TO FOLLOW-UP 
A subject will be considered lost to follow-up if he/she fails to attend a scheduled study Visit 
(including treatments) and cannot be contacted by the study site staff, subject to the completion 
of the action detailed below: 
− Within 2 days from the original missed study Visit, the site will attempt to contact the 
subject and reschedule the missed visit. The site will counsel the subject on the 
importance of maintaining the assigned visit schedule and ascertain if the subject wishes 
to and/or should continue in the study. 
− Before a subject is deemed lost to follow-up, the Investigator or designee will make every 
effort to regain contact with the participant and his/her caregiver/s (where possible, 3 
telephone calls and, if necessary, a certified letter to the subject’s last known mailing 
address or local equivalent methods, a visit to subject’s last known address where 
reasonable). These contact attempts should be documented in the subject’s medical 
record or study file.  
− Should the subject continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 

 
 
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8 
STUDY ASSESSMENTS AND PROCEDURES 
8.1 
EFFICACY ASSESSMENTS 
The order of and timeline of the screening procedures and evaluations (Visit 1) are presented in 
the study schema (please refer to § 1.2) and the schedule of activities (please refer to § 1.3). 
The questionnaires and functional tests detailed below are appended to this protocol (please refer 
to § 12.1). 
mRS (first screening procedure after consent is obtained) 
The mRS is a 7-level scale with possible scores ranging from 0 (no symptoms at all) through 5 
(severe disability) and 6 (death) and is used for measuring the degree of disability or dependence 
in the daily activities of people who have suffered a stroke or other causes of neurological 
disability (76). The mRS is the most frequently used outcome measure in stroke trials (77). To 
increase outcome comparability and minimize bias, the modified Rankin Scale assessments of 
global disability will be obtained at all sites using the formal, algorithmic Rankin Focused 
Assessment-Ambulatory (RFA-A) method by RFA-A-certified raters (78-80). The formal RFA-
A elicitation technique is an NIH trial-developed method for assigning mRS scores validated to 
improve inter-rater reliability in assigning mRS scores. In addition, the RFA-A method to assign 
mRS scores has been employed for primary and second endpoint ascertainment in numerous 
FDA-regulated drug and device trials (47, 81-83). 
Fugl-Meyer Assessment-Upper extremity (FMA-UE; second screening procedure)  
The Fugl-Meyer Assessment is a stroke-specific, performance-based impairment index. It is 
designed to assess motor functioning, balance, sensation and joint functioning in patients with 
post-stroke hemiparesis (84, 85). It is frequently applied clinically and in research to determine 
disease severity, describe motor recovery, and to plan and assess rehabilitation treatment (86). 
This test is one of the most used instruments in rehabilitation and its validity and reliability has 
established validity, reliability, and sensitivity to treatment-related change (84, 87, 88). 
In this study, the index will be used to assess the motor impairment of the upper extremity after 
stroke. Each movement will be graded on a 3-point scale, and the total score will range 0–66 
points ,with a higher score representing more active movements.  

 
 
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Box and Block Test (BBT)  
The Box and Block Test is a quick and simple test which measures unilateral upper extremity 
function (89). In the BBT, one hundred and fifty 2.5-cm3 wooden blocks in many different 
orientations are placed on the side of the partition with the testing hand. A subject’s score is 
equal to the number of these blocks transported over a 15.2-cm–tall partition in one minute. The 
subject can select blocks in any order to transport over the partition as quickly as possible, with 
the only requirement being that the subject’s fingertips cross the vertical plane of the partition 
(90). 
Stroke Impact Scale (SIS) Hand-Domain and SIS-16  
The Stroke Impact Scale is a patient reported outcome instrument designed to assess physical 
function in patients with stroke. This outcome measure developed in the United States by 
Duncan et al (91, 92) and has undergone considerable validation and development. The SIS was 
designed for in-person use, but can be administered via phone or mail, too. The SIS Hand-
Domain (SIS version 3.0) assesses hand function, including activities dependent upon grip, pinch 
strength, and finger dexterity (93).  
The SIS-16 assesses physical function, including activities dependent upon upper extremity, 
lower extremity, trunk, and gait motion (94).  
EQ-5D-5L 
The EuroQol-5 Dimension (EQ-5D), developed in 1990, is a widely used generic tool to measure 
generic health-related quality of life (HRQoL) using three levels of severity in five dimensions 
(95). In 2009, the EuroQol Group developed a new EQ-5D version to overcome limitations 
related to its consistently reported high ceiling effect. To enhance the sensitivity for assessing 
HRQoL in further patient populations, the number of responses for each section of the EQ-5D 
was increased from 3 to 5 levels (EQ-5D-5L; (95)). EQ-5D scores can be converted to patient-
specific health utilities that are used in the calculation of quality-adjusted life years and 
evaluating the cost-effectiveness of medical therapies. 
10-meter walk test (10MWT) 
The 10-meter walk test is a simple assessment to measure locomotor capacity in clinical and 
research settings. The individual walks alone or with assistance of no more than one person and 
their gait velocity is quantified. Assistive devices which are normally used for balance and/or 
stability (eg, cane or walker) are allowed. Individuals are requested to walk the said distance in 
their usual or normal pace. The mean velocity of gait has been termed the sixth vital sign (96) 
because of its very high clinical, research, and real-world relevance. 

 
 
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Academic Medical Center Linear Disability Score (ALDS)  
The Academic Medical Center Linear Disability Score is a generic item bank that measures the 
disability status of patients with a broad range of diseases, as expressed by the ability to perform 
activities in daily living (97). Using the ALDS, disability level can be quantified in a granular 
fashion on a continuous scale, using ~15 items tailored to the particular general functional level 
of each patient. 
MoCA 
The Montreal Cognitive Assessment is a widely used screening assessment for detecting 
cognitive impairment developed in Montreal Canada. It is a one-page, 30-point test administered 
in approximately 10 minutes (98). 
PHQ-8 
The Patient Health Questionnaire (PHQ) is a self-administered version of the PRIME-MD 
diagnostic instrument for common mental disorders (99). The PHQ-8 is composed of 8 items that 
assess for depression based on DSM-IV criteria, with each item rated between “0” (not at all) to 
“3” (nearly every day) (99). The PHQ is an instrument for making criteria-based diagnoses of 
depressive and other mental disorders commonly encountered in primary care. The PHQ-8 does 
not include the ninth item of the PHQ-9, as that item has been found not to be reliable and the 
PHQ-8 performs comparably to the PHQ-9. The PHQ-8 is half the length of many other 
depression measures, has comparable sensitivity and specificity (99). The PHQ-8 is more 
efficient than “2-step” depression measures for which, when scores are high, additional questions 
must be asked to establish DSM-IV depressive diagnoses. Specifically, the diagnostic validity of 
the PHQ in post-stroke patients has been established in several studies (102-110).  
8.1.1 STUDY VISITS 
8.1.1.1 PRE-SCREENING PHASE  
Prospective subjects, who are 3 to 21 days post-stroke, can be consented to participate in the 
study at a participating initial acute care hospital (ACH) prior to anticipated discharge to a 
participating IRF, SNF, outpatient, or home setting. Alternatively, prospective subjects, who are 
3 to 21 days post-stroke, can be consented at a participating IRF, SNF, outpatient, or home 
setting. 
Only brief eligibility review to determine initial eligibility and interest in the study will be 
performed prior to elicitation of consent.  

 
 
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8.1.1.2 SCREENENG & ENROLLMENT, BASELINE VISIT 
 
Efforts should be made to complete enrolment, randomization and initiate treatments as early as 
possible within the window of recruitment, and target to complete a first treatment within 4 
weekdays from admission to the participating site. 
For consented subjects, the following additional data will be recorded at this visit: 
− Demographics – age, sex, race/ethnicity  
− Medical history - presence of concomitant medical conditions (eg, hypertension, diabetes, 
hyperlipidemia, atrial fibrillation, prior ischemic stroke, prior hemorrhagic stroke, current 
or past smoking) 
− Vital signs – temperature, pulse, blood pressure. 
− Concomitant medications – any concomitant medications by or administered to the 
subject at the time of screening (for details, refer to § 6.5). 
− In women of childbearing potential a urine or blood test will be performed unless there is 
a documentation of a negative pregnancy test in an official medical documentation. 
− mRS 
− FMA-UE, 
− BBT, 
− 10MWT 
− SIS Hand Domain, 
− SIS-16, 
− SAFE 
− NIHSS 
− Any adverse events  
Consented subjects, who are 4 to 21 days post-stroke, and have passed screening for eligibility 
will advance to the treatment phase of the study, commencing with randomization. 
Randomization should be performed within 24 hours from the mRS and FMA-UE assessments. 
If more than 24 hours have elapsed, these assessments should be repeated and only those subjects 
whose reassessed scores for both assessments conform with the eligibility criteria will be 
randomized. The later scores will serve as the baseline scores and for stratification. 
Eligible subjects will be randomly assigned, at a 1:1 allocation ratio, to either the active or sham 
study intervention groups. 
The following additional data will be obtained after randomization and not later than Midterm 
follow-up visit: 

 
 
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− Imaging Data – there will be no imaging tests performed in the study. However, for 
subjects randomized to the study, all computed tomography (CT), CT angiography 
(CTA), CT perfusion (CTP), and brain magnetic resonance imaging (MRI) 
perfusion/diffusion-weighted imaging (DWI/PWI) / fluid attenuated inversion recovery 
brain magnetic resonance angiography (FLAIR), and brain magnetic resonance 
angiography (MRA) studies available from the first 7 days in the ACH will be transferred 
to the sponsor by either using CD's or via an online cloud based service. If multiple 
images are available from different recording sessions at the acute stay, it is required to 
collect the first image and the last image27. Please refer to the study MOP for instructions. 
− The following values from the complete blood count performed at the time the subject 
was admitted and diagnosed with stroke will be transcribed into the CRF: 
o red blood cell distribution width (an independent predictor of 3-month functional 
outcome; (111)) 
o absolute white cell count (an independent predictor of stroke severity and degree 
of disability; (112)) 
8.1.1.3 TREATMENTS 1-20 
Randomized subjects will undergo the first treatment session no later than 48 hours after 
randomization and within 4-21 days after stroke onset. Active or sham study intervention 
sessions using BQ 2.0 (active or sham therapy, respectively) will be conducted 5 times a week, 
for approximately 9 weeks and until completion of 45 treatment sessions, conducted in either 
inpatient, outpatient or home setting. 
At each of these visits, the subject will undergo a study treatment. Each treatment session will 
last up to 60 minutes, with active or sham field being turned on for the first 40 minutes. During 
the session, subjects will be asked to perform a device guided, standardized, pre-defined and 
evidence-based PT/OT therapy activities, with approximately 30 minutes dedicated to the upper 
extremity and 30 minutes to the lower extremity, aligned with the Class 1 level A 
recommendation for patients with stroke to participate in a home-based rehabilitation program.  
A trained member of the site study team (the “Clinic Operator”) will be responsible for training 
and approving the subject’s caregiver to operate the session independently.  
 
 
27 MRI images will be preferred over CT images 

 
 
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Before an approval to operate a session independently (the “Approval”) is granted by the Clinic 
Operator, a Clinic Operator will train the caregiver and supervise the sessions, either in-person or 
remotely. Once an Approval was granted, sessions will be conducted with the assistance of a 
caregiver while the Clinic Operator will provide periodic oversight (combined audio and video 
remote conferencing or audio only, if video is not available). If needed, and at their discretion, 
the Clinic Operator may join sessions following the Approval too. 
At each of these visits, the following data will be collected: 
− Any changes in concomitant medications 
− Any adverse events 
− Any device deficiencies 
− Duration of stimulation delivered and number of pauses if occurred 
− Duration of PT/OT activities performed during the 60-minute period 
− PT/OT activities performed outside of study since last visit 
8.1.1.4 MIDTERM FOLLOW-UP VISIT (IN CLINIC) 
This visit will take place in the clinic (±4 days from the 20th treatment). Though, in special 
circumstances and subject to the approval of the Principal Investigator, the visit can be 
conducted in an out-patient setup or via combined audio and video remote conferencing or audio 
only, if video is not available.   
The following assessments (described in § 8.1) will be performed during this visit: 
− mRS, 
− FMA-UE, 
− BBT, 
− SIS Hand Domain, 
− SIS-16 
At this visit, the following data will be collected as well: 
− Vital signs 
− Any changes in concomitant medications 
− Any adverse events 
− Any device deficiencies 
− PT/OT activities performed outside of study since last visit 
− Use of healthcare resources   

 
 
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At this visit day, a treatment session may or may not take place, in accordance to the availability 
of the subject and/or the site. If a session will not take place, and unless completed over the 
weekend, 4 treatment sessions will take place in that week.  
If a treatment session is to take place at the same day of the assessment, the session may be 
conducted only after the assessments were completed to avoid changing outcome measure scores 
due to subject fatigue.  
8.1.1.5 TREATMENTS 21-45 
At each of these visits, the subject will undergo a study treatment. Each treatment session will 
last up to 60 minutes, with active or sham field being turned on for the first 40 minutes. During 
the session, subjects will be asked to perform a device guided, standardized, pre-defined and 
evidence-based PT/OT with approximately 30 minutes dedicated to the upper extremity and 30 
minutes to the lower extremity aligned with the Class 1 level A recommendation for patients 
with stroke to participate in a home-based rehabilitation program.  
At each of these visits, the following data will be collected: 
− Any changes in concomitant medications 
− Any adverse events 
− Any device deficiencies 
− Duration of stimulation delivered and number of pauses if occurred 
− Duration of PT/OT activities performed during the 60-minute period 
PT/OT activities performed outside of study since last visit  
 
8.1.1.6 DAY 90 PRIMARY OUTCOME ASSESSMENT VISIT (IN CLINIC) 
This visit will take place in the clinic. Though, in special circumstances and subject to the 
approval of the Principal Investigator, the visit can be conducted in an out-patient setup or via 
combined audio and video remote conferencing or audio only, if video is not available. 
The following assessments (described in § 8.1) will be performed during this visit: 
− mRS, 
− FMA-UE, 
− BBT, 
− 10MWT 
− SIS Hand Domain, 
− SIS-16, 

 
 
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− EQ-5D-5L 
− ALDS, 
− MoCA, 
− PHQ-8, 
At this visit, the following data will be collected: 
− Vital signs 
− Any changes in concomitant medications 
− Any adverse events 
− Any device deficiencies 
− PT/OT activities performed outside of study since last visit 
− Use of healthcare resources   
Additionally, at this visit, the subjects will be asked to rate their certainty regarding group 
allocation by selecting one of five options: (1) knew they had received active stimulation; (2) 
thought they received active stimulation; (3) knew they were in the sham stimulation group; (4) 
thought they were in the sham stimulation group; or (5) did not know which treatment group they 
were allocated. 
8.1.1.7 DAY 180 ADDITIONAL FOLLOW-UP VISIT  
This additional follow up will be conducted remotely via combined audio and video remote 
conferencing (or audio only, if video is not available), or in-person, if preferred.  
The following assessments (described in § 8.1) will be performed during this visit: 
− mRS 
− SIS Hand Domain, 
− EQ-5D-5L 
At this visit, the following data will be collected: 
− Any adverse events 
− Any changes in concomitant medications 
− Use of healthcare resources   

 
 
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8.2 
SAFETY AND OTHER ASSESSMENTS 
The following procedures/evaluations will be performed to assess safety in this study in addition 
to the descriptions already described above in this § 8. 
Assessment of adherence to investigational product use. Please refer to § 6.4. 
Assessment of adverse events. Adverse events will be assessed for severity, seriousness, 
expectedness, action taken, and relation to the study device and procedure and recorded at each 
study Visit, at which time the subject will provide data on all adverse events that occurred since 
the last Visit. Please refer to §§ 8.3.1, 8.3.4, 8.3.5, and 8.3.8 for adverse event definitions, period 
of reporting, reporting specifications, and events of special interest. 
8.3 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
8.3.1 DEFINITION OF ADVERSE EVENTS (AE) 
Adverse event (AE) is any untoward medical occurrence, unintended disease or injury, or 
untoward clinical signs (including abnormal laboratory findings) in subjects, users or other 
persons, whether or not related to the investigational medical device and whether anticipated or 
unanticipated. This definition includes events related to the investigational medical device or the 
comparator28. This definition includes events related to the procedures involved. For users or 
other persons, this definition is restricted to events related to investigational medical device or 
comparators. 
AEs include any event having been absent at baseline, or, if present at baseline (medical history), 
subsequently worsening. 
Adverse device effect (ADE) is an adverse event related to the use of an investigational medical 
device. This definition includes adverse events resulting from insufficient or inadequate 
instructions for use, deployment, implantation, installation, or operation, or any malfunction of 
the investigational medical device. This definition includes any event resulting from use error29 
 
28 Comparator is a medical device, therapy (eg, active treatment, normal clinical practice), placebo or no 
treatment, used in the control group in a clinical investigation (ISO 14155:2020 § 3.12) 
29 ISO 14971:2019 (definition 3.30): user action or lack of user action while using the medical device that leads to a 
different result than that intended by the manufacturer or expected by the user. Use error includes the inability of the 
user to complete a task. Use errors can result from a mismatch between the characteristics of the user, user interface, 
task, or use environment. Users might be aware or unaware that a use error has occurred. An unexpected 
physiological response of the patient is not by itself considered use error. A malfunction of a medical device that 
causes an unexpected result is not considered a use error. 

 
 
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or from intentional misuse of the investigational medical device. This includes comparator if the 
comparator is a medical device. 
Device deficiency is an inadequacy of a medical device with respect to its identity, quality, 
durability, reliability, usability, safety or performance. Device deficiencies include malfunctions, 
use errors, and inadequacy in the information supplied by the manufacturer including labelling. 
This definition includes device deficiencies related to the investigational medical device or the 
comparator.30 
8.3.2 DEFINITION OF SERIOUS ADVERSE 
EVENTS (SAE)  
Serious adverse device effect (SADE) is an adverse device effect that has resulted in any of the 
consequences characteristic of a serious adverse event. 
Serious adverse event (SAE) is an adverse event that that led to any of the following 
a. 
death, 
b. 
serious deterioration in the health of the subject, users or other persons as defined by 
one or more of the following: 
1. 
a life-threatening illness or injury, or 
2. 
a permanent impairment of a body structure or a body function including 
chronic diseases, or 
3. 
in-patient or prolonged hospitalization, or 
4. 
medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function, 
c. 
fetal distress, fetal death or a congenital abnormality or birth defect including 
physical or mental impairment 
NOTE: Planned hospitalization for a pre-existing condition, or a procedure required by the 
clinical investigation protocol, without serious deterioration in health, is not considered a serious 
adverse event. 
8.3.3 CLASSIFICATION OF AN ADVERSE EVENT 
 
30 The part of the device deficiency definition appearing in italics is introduced in ISO 14155:2020 and is absent 
from the definition available in CHAPTER I Article 2(59) of the MDR. For the purposes of this trial, the definition 
in this protocol will apply for Investigator reports to the Sponsor. Applicability of the gap between the definitions in 
this protocol and the aforementioned MDR definition will be assessed for Sponsor reports to National Competent 
Authorities if and where MDR will apply to this trial. 

 
 
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8.3.3.1 SEVERITY OF EVENT 
All events will be graded according to the National Cancer Institute Common Terminology 
Criteria for Adverse Events (NCI CTCAE) Version 5.0 available on:  
https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_5.0/ 
Grade refers to the severity of the AE. The CTCAE v.5.0 displays Grades 1 through 5 with 
unique clinical descriptions of severity for certain AEs based on a general guideline shown in 
Table 3 below. 
Table 3. NCI CTCAE v.5.0 grading system 
Grade 1 
Mild 
Asymptomatic or mild symptoms; clinical or 
diagnostic observations only; intervention not 
indicated. 
Grade 2 
Moderate 
Minimal, local or noninvasive intervention indicated; 
limiting age-appropriate instrumental ADL*. 
Grade 3 Severe or medically significant but 
not immediately life-threatening; 
Hospitalization or prolongation of hospitalization 
indicated; disabling; limiting self-care ADL**. 
Grade 4 
Life-threatening consequences 
Urgent intervention indicated. 
Grade 5 
Death related to AE. 
 
*Instrumental ADL (Activities of Daily Living) refer to preparing meals, shopping for groceries or clothes, using the telephone, 
managing money, etc.  
**Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden. 
For events not listed in the CTCAE toxicity table, severity should be assessed using the general 
CTCAE grading guideline provided in Table 3. 
8.3.3.2 RELATIONSHIP TO STUDY INTERVENTION 
For all collected AEs, the Investigator who examines and evaluates the subject will provide the 
Sponsor with his/her assessment of the AE causality based on temporal relationship and his/her 
clinical judgment31. The degree of certainty about causality will be graded using the categories in 
Table 4 below32.  
 
31 Procedure related events refers to the procedure related to the initial application of the investigational medical 
device only and therefore not to any other procedures or treatments applied later throughout the clinical 
investigation, for instance to treat (serious) adverse events (MEDDEV 2.7/3 revision 3 - GUIDELINES ON 
MEDICAL DEVICES - CLINICAL INVESTIGATIONS: SERIOUS ADVERSE EVENT REPORTING UNDER 
DIRECTIVES 90/385/EEC AND 93/42/EEC) 
32 Based on the EU medical device coordination group (MDCG) guidance 2020-10/1 Safety reporting in clinical 
investigations of medical devices under the Regulation (EU) 2017/745. Although originally proposed for serious 
adverse events, it is suitable for non-serious events as well. 

 
 
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The Sponsor and the Investigators will distinguish between the serious adverse events related to 
the investigational device, those related to the procedures (any procedure specific to the clinical 
investigation), and those unrelated to either the investigational device or study procedures. An 
adverse event can be related both to procedures and the investigational device.33  
 
Table 4. Causality of adverse events 
Not related 
Relationship to the device, comparator or procedures can be excluded when: 
– the event has no temporal relationship with the use of the investigational device, or the 
procedures related to application of the investigational device; 
– the serious adverse event does not follow a known response pattern to the medical 
device (if the response pattern is previously known) and is biologically implausible; 
– the discontinuation of medical device application or the reduction of the level of 
activation/exposure - when clinically feasible - and reintroduction of its use (or increase 
of the level of activation/exposure), do not impact on the serious adverse event; 
– the event involves a body-site or an organ that cannot be affected by the device or 
procedure; 
– the serious adverse event can be attributed to another cause (eg, an underlying or 
concurrent illness/ clinical condition, an effect of another device, drug, treatment or 
other risk factors); 
– the event does not depend on a false result given by the investigational device used for 
diagnosis34, when applicable; 
In order to establish the non-relatedness, not all the criteria listed above might be met at the 
same time, depending on the type of device/procedures and the serious adverse event. 
Possible 
The relationship with the use of the investigational device or comparator, or the relationship 
with procedures, is weak but cannot be ruled out completely. Alternative causes are also 
possible (e.g. an underlying or concurrent illness/ clinical condition or/and an effect of 
another device, drug or treatment). Cases where relatedness cannot be assessed, or no 
information has been obtained should also be classified as possible. 
Probable 
The relationship with the use of the investigational device or comparator, or the relationship 
with procedures, seems relevant and/or the event cannot be reasonably explained by another 
cause. 
Causal 
relationship 
The serious adverse event is associated with the investigational device, comparator or with 
procedures beyond reasonable doubt when: 
– the event is a known side effect of the product category the device belongs to or of 
similar devices and procedures; 
 
33 Complications caused by concomitant treatments not imposed by the clinical investigation plan are considered not 
related. Similarly, several routine diagnostic or patient management procedures are applied to patients regardless of 
the clinical investigation plan. If routine procedures are not imposed by the clinical investigation plan, complications 
caused by them are also considered not related. 
34 If an investigational device gives an incorrect diagnosis, the patient might, for example, receive an unnecessary 
treatment and incur all the risks that accompany that treatment, or might be incorrectly diagnosed with a serious 
disease. In other cases, the patient might not receive an effective treatment (thereby missing out on the benefits that 
treatment would confer) or might not be diagnosed with the correct disease or condition. 

 
 
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– the event has a temporal relationship with investigational device use/application or 
procedures; 
– the event involves a body-site or organ that  
o the investigational device or procedures are applied to; 
o the investigational device or procedures have an effect on;  
– the serious adverse event follows a known response pattern to the medical device (if the 
response pattern is previously known); 
– the discontinuation of medical device application (or reduction of the level of 
activation/exposure) and reintroduction of its use (or increase of the level of 
activation/exposure), impact on the serious adverse event (when clinically feasible); 
– other possible causes (eg, an underlying or concurrent illness/ clinical condition or/and 
an effect of another device, drug or treatment) have been adequately ruled out; 
– harm to the subject is due to error in use; 
– the event depends on a false result given by the investigational device used for 
diagnosis35, when applicable; 
In order to establish the relatedness, not all the criteria listed above might be met at the same 
time, depending on the type of device/procedures and the serious adverse event. 
The Sponsor is responsible for the classification of adverse events and ongoing safety evaluation 
of the clinical investigation. The Sponsor or Sponsor’s designee (Medical Monitor/Expert36) 
shall review the Investigator's assessment of all adverse events and determine and document in 
writing their seriousness and relationship to the investigational device and the procedure; in case 
of disagreement between the Sponsor and the Investigator(s), BrainQ Technologies Ltd. shall 
communicate both opinions to concerned parties37 (refer to § 8.3.6 for details on reporting of 
serious adverse events), unless otherwise instructed by a local regulation or guidance. 
 
35 If an investigational device gives an incorrect diagnosis, the patient might, for example, receive an unnecessary 
treatment and incur all the risks that accompany that treatment, or might be incorrectly diagnosed with a serious 
disease. In other cases, the patient might not receive an effective treatment (thereby missing out on the benefits that 
treatment would confer), or might not be diagnosed with the correct disease or condition 
36 Clinical Data Interchange Standards Consortium (CDISC) glossary item C51836 defines Medical Monitor as “A 
sponsor representative who has medical authority for the evaluation of the safety aspects of a clinical trial.” The US 
FDA Compliance Program 7348.810 BIORESEARCH MONITORING Guidance for FDA Staff on “SPONSORS, 
CONTRACT RESEARCH ORGANIZATIONS AND MONITORS” (April 2017) clarifies that Medical Monitor 
may have the responsibility for 
medical aspects of the study (and may be a physician) while other Monitors may assess regulatory compliance. 
ICH GCP E6(R2) defines medical expert as medical personnel who will be readily available to advise on trial 
related medical questions or problems. 
ISO 14155:2020 notes that medical expertise is provided by a person qualified by education, training and 
experience, who is readily available to advise on the clinical investigation and related medical questions or 
problems. If necessary, outside consultant(s) can be available for this purpose. 
37 § 8.2.5(a) of EN ISO 14155:2011/AC:2011 and § 9.2.5(a) of ISO 14155:2020, and MEDDEV 2.7/3 revision 3 

 
 
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8.3.3.3 EXPECTEDNESS  
Risk analysis conducted by BrainQ Technologies Ltd. shall be used as a basis for identifying 
anticipated AEs/ADEs characterized by their nature, incidence, severity, and outcome. In 
general, an AE/ADE will be considered unexpected if the nature, severity, or frequency of the 
event is not consistent with the risk information previously described for the investigational 
device. The potential expected (anticipated) side effects, based on the risk analysis, are listed in 
§ 2.3.1 above.  
SAEs known to occur with a frequency >1% in the normal course of patients with acute ischemic 
stroke under standard medical management will generally be rated as attributable to the subject’s 
underlying condition (please refer to the list provided as an appendix to the MOP). 
For reporting to regulatory authorities, the Sponsor or Sponsor’s designee (Medical 
Monitor/Expert) will be responsible for determining whether an SAE/SADE is expected 
(anticipated) or unexpected (unanticipated) in this study38. 
8.3.4 TIME PERIOD AND FREQUENCY FOR 
EVENT ASSESSMENT AND FOLLOW-UP 
Investigators or designee will record all qualifying events (adverse events and device 
deficiencies) with start dates occurring any time after informed consent is obtained until the last 
day of study participation. At each study Visit, the Investigator or designee will inquire about the 
occurrence of AE/SAEs since the last visit and or last treatment. Only SAEs unresolved at the 
last study visit will be followed for outcome information until resolution or until assessed as 
chronic or stable. 
8.3.5 ADVERSE EVENT AND DEVICE 
DEFICIENCY REPORTING  
The occurrence of an AE or SAE may come to the attention of study personnel during study 
Visits and interviews of a study subject presenting for medical care, or upon review by a study 
Monitor. 
All AEs including local and systemic reactions will be captured on the appropriate CRF. 
Information to be collected includes event description, (and time, for serious events occurring 
during the study procedure) onset, Investigator’s assessment of severity, seriousness, relationship 
 
38 Per the recommendation in the US FDA “Guidance for Clinical Investigators, Sponsors, and IRBs Adverse Event 
Reporting to IRBs - Improving Human Subject Protection” (§§ III.B and IV), and in agreement with §§ 812.46(b), 
812.150(b)(1), and § 8.2.5 of ISO 14155:2011/COR1:2011 and § 9.2.5 of ISO 14155:2020. 

 
 
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to study device/procedure (assessed only by those with the training and authority to make a 
diagnosis), expectedness, date (and time, for serious events occurring during the study 
procedure) of resolution/stabilization of the event, where applicable; and any action taken. All 
AEs occurring while on study must be documented appropriately regardless of relationship. 
During the study, all AEs will be followed to adequate resolution or stabilization. In case of 
adverse events that are still unresolved at the final study Visit; refer to § 8.3.4 for guidance on 
event follow-up. 
Any medical condition that is present at the time that the participant is screened will be 
considered as baseline and not reported as an AE (refer to § 8.3.1). However, if the study 
subject’s condition deteriorates at any time during the study, it will be recorded as an AE. The 
AE term in the latter case must be the same term entered at baseline for the preexisting condition 
and must start with "Worsening of…/ Deterioration of… ". 
Changes in the severity of an AE will be documented to allow an assessment of the duration of 
the event at each level of severity to be performed. If an ongoing AE worsens in its severity or its 
relationship to the study device or procedure changes, a new AE entry for the event should be 
entered on the CRF while the preceding event record should be reported as ended on the same 
date (113). AEs characterized as intermittent require documentation of onset and duration of 
each episode. 
Laboratory safety measurements and variables reporting 
The treating site will perform laboratory analyses according to the protocol-defined Visit 
schedules and determine protocol-defined parameters. A tabulation of the normal ranges for each 
parameter required will be enclosed with the measurements done. If at any time a subject has 
laboratory parameters obtained from a different laboratory, the normal ranges for that laboratory 
must be recorded with the result obtained. At any time during the trial, abnormal laboratory 
parameters which are clinically relevant (eg, which lead to interruption of trial treatment, or 
which lead to clinical symptoms or signs requiring therapeutic intervention), whether specifically 
requested in the protocol or not, must be recorded on the appropriate CRF form. When abnormal 
laboratory parameters or test results constitute an SAE, a complete SAE report on the SAE 
Report form must also be provided. 
Notification of deaths 
All deaths must be reported to the Sponsor, irrespective of whether the death is related to the 
device and/or procedure or is an unrelated event. If multiple adverse events are considered to be 
“causes of death”, each event must be entered as a separate AE record. Whenever a subject dies 
and there is no known cause of death, with no AEs to which the death can be attributed (death 

 
 
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certificate indicates no known cause of death), the AE Term must be entered as “Unknown cause 
of death”. 
Device deficiencies 
Device deficiencies will be reported on the appropriate CRF form. 
Device deficiencies that did not lead to an adverse event but could have led to a serious adverse 
device effect 
a. 
if suitable action had not been taken, or 
b. 
if intervention had not been made, or 
c. 
if circumstances had been less fortunate, 
shall be reported as an SAE (please refer to § 8.3.6). 
8.3.6 SERIOUS ADVERSE EVENT REPORTING  
Investigator’s Responsibilities 
Collection, recording, and reporting of SAEs/SADEs or device deficiencies that could have led 
to a SADE by Investigators to the Sponsor, including any unexpected serious adverse events or 
serious health threats (refer to § 8.4 below), will be done in an expedited manner using the 
AE/SAE Report form. Any intercurrent illness, medications, and/or conditions must also be 
recorded using the relevant CRF form, in the normal manner. All AEs defined as serious and any 
device deficiencies that could have led to a SADE should be reported to the Sponsor by the 
Investigator within a very short period of time and under no circumstances should this exceed 24 
hours following knowledge of the SAE39. Receipt of SAE reports will be acknowledged by the 
Sponsor. 
Contact details for safety reporting purposes: 
Assaf Lifshitz 
Email: assaf@brainqtech.com 
 
39 In agreement with the US FDA “Guidance for Industry and Investigators Safety Reporting Requirements for 
INDs and BA/BE Studies” (December 2012) and the provisions of § 7.2 of the EC Guidance on “Clinical 
Investigations: Serious Adverse Event Reporting under Directives 90/385/EEC and. 93/42/EEC” (MEDDEV 2.7/3 
revision 3, May 2015). 

 
 
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Sponsor’s Responsibilities 
Reporting of serious adverse events by the Sponsor to regulatory authorities40 will be done in 
accordance with the standard operating procedures (SOPs) of the Sponsor or designee (eg, 
contract research organization [CRO]) and the appropriate regulatory requirements41.  
In general, reportable events42 will be reported at the same time to all regulatory authorities in 
whose jurisdiction this clinical investigation has commenced. 
Data and Safety Monitoring Board (DSMB) be established in the study under the provisions of 
§ 10.1.6. BrainQ Technologies Ltd. will also report all relevant safety information to the DSMB, 
according to written procedures.  
8.3.7 REPORTING EVENTS TO PARTICIPANTS  
Not applicable. 
8.3.8 EVENTS OF SPECIAL INTEREST  
Adverse events severity of which corresponds to Grade 3 or higher on the CTCAE v.5.0 scale 
and that have “probable”, “possible“ or “causal” relationship with the device and/or the 
procedure, in accordance with the causality of adverse events as presented in Table 4, must be 
reported to the Sponsor within 24 hours following the awareness by study personnel at a 
participating site, unless such events meet the definition of a serious adverse event provided in 
§ 8.3.2, in which case their reporting must adhere to the provisions of § 8.3.6 of this protocol. 
8.3.9 REPORTING OF PREGNANCY  
Any pregnancy within the term of participation of a subject in the study must be reported by 
Investigator to the Sponsor. The pregnancy should then be followed-up by the Investigator to 
determine outcome, including spontaneous or voluntary termination, and the presence or absence 
of any birth defects, congenital abnormalities, or maternal and/or newborn complications. 
 
40 These are referred to as National Competent Authorities (NCAs) in the European Union 
41 In the United States, this will be done in accordance with 21 CFR 812 812.150(b) 
42 The part of the serious adverse event definition in § 8.3.2 appearing in italics is introduced in ISO 14155:2020 is 
absent from the definition available in CHAPTER I Article 2(58) of the MDR. For the purposes of this trial, the 
definition in this protocol will apply for Investigator reports to the Sponsor. Applicability of the gap between the 
definitions in this protocol and the aforementioned MDR definition will be assessed for Sponsor reports to National 
Competent Authorities if and where MDR will apply to this trial. 

 
 
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NOTE: Pregnancy follow-up does not extend the study for each subject and no data will be 
collected after the specified study duration for each subject. 
8.4 
UNANTICIPATED PROBLEMS 
8.4.1 DEFINITION OF UNANTICIPATED 
PROBLEMS (UP) 
Unanticipated problems involving risks to participants or others will include, in general, any 
incident, experience, or outcome that meets all of the following criteria: 
− Unexpected in terms of nature, severity, or frequency, given a) the research procedures 
that are described in the protocol-related documents, such as the IRB/EC-approved 
research protocol and informed consent document; and b) the characteristics of the 
participant population being studied; 
− Related or possibly related to participation in the research (“possibly related” means there 
is a reasonable possibility that the incident, experience, or outcome may have been 
caused by the procedures involved in the research); and 
− Suggests that the research places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or 
recognized. 
For this study, UPs include43: 
– Unanticipated adverse device effect (UADE44) – any serious adverse effect on health or 
safety or any life-threatening problem or death caused by, or associated with, a device, if 
that effect, problem, or death was not previously identified in nature, severity, or degree 
of incidence in the investigational plan or application (including a supplementary plan or 
application), or any other unanticipated serious problem associated with a device that 
relates to the rights, safety, or welfare of subjects. 
– Serious health threat is a signal from any adverse event or device deficiency that 
indicates an imminent risk of death or a serious deterioration in the health in subjects, 
users or other persons, and that requires prompt remedial action for other subjects, users 
or other persons45. 
 
43 Per the recommendation in the US FDA “Guidance for Clinical Investigators, Sponsors, and IRBs Adverse Event 
Reporting to IRBs - Improving Human Subject Protection” (§§ III.B and IV), and in agreement with 21 CFR §§ 
812.46(b), 812.150(a)(1), 812.150(b)(1) and § 9.2.5 of ISO 14155:2020. 
44 Refer to 21 CFR 812.3(s). Consistent with the language defining the unanticipated serious adverse device effect 
(USADE) in § 3.42 of EN ISO 14155:2011/AC:2011 and § 3.51 of ISO 14155:2020. 
45 § 3.46 of ISO 14155:2020 

 
 
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NOTE: This would include events that are of significant and unexpected nature such that 
they become alarming as a potential serious health hazard or possibility of multiple 
deaths occurring at short intervals. 
8.4.2 UNANTICIPATED PROBLEM REPORTING  
An Investigator shall submit to the Sponsor and, if required, to the reviewing IRBs/ECs (and, 
where applicable, regulatory authority) a report of any unanticipated problem occurring during 
an investigation46. The Sponsor will conduct evaluation of unanticipated problems47 and report 
the results of such evaluation to regulatory authorities and to all reviewing IRBs/ECs and 
participating Investigators. 
If an UADE presents an unreasonable risk to subjects, the Sponsor shall terminate all 
investigations or parts of investigations presenting that risk as soon as possible. Termination 
shall occur not later than 5 working days after the Sponsor makes this determination and not later 
than 15 working days after the sponsor first received notice of the effect. The Sponsor will not 
resume a terminated investigation without IRB/EC and the U.S. FDA approval48. 
The results of Sponsor’s evaluation of unanticipated problems will be reported to the U.S. FDA 
and to all reviewing IRB's and participating Investigators within 10 working days after the 
Sponsor first receives notice of the effect49. Thereafter the sponsor shall submit such additional 
reports concerning the effect as FDA requests. 
8.4.3 REPORTING UNANTICIPATED PROBLEMS 
TO PARTICIPANTS  
Not applicable. 
9 
STATISTICAL CONSIDERATIONS  
9.1 
STATISTICAL HYPOTHESES 
− Null hypothesis: 
Mean change in mRS score from baseline (post-stroke day 4-21) to the end of study visit (90 
±15 days post-stroke) in the BQ 2.0 group = mean change in the sham group. 
 
46 Timelines for reporting to the Sponsor are outlined in § 8.3.6. For IRB reporting in the United States, 
Investigators should follow the timelines delineated in 21 CFR812.150(a)(1).  
47 21 CFR 812.46 and § 7.4.4 of ISO 14155:2020 
48 21 CFR 812.46 and § 8.2.1 of ISO 14155:2020 
49 21 CFR 812.150(b)(1) § 7.4.4 of ISO 14155:2020 

 
 
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− Alternative hypothesis:  
Mean change in mRS score from baseline (post-stroke day 4-21) to the end of study visit (90 
±15 days post-stroke) in the BQ 2.0 group ≠ mean change in the sham group. 
9.2 
SAMPLE SIZE DETERMINATION 
A sample size is calculated to test the null hypothesis with 80% power at a 5% two-sided level of 
significance using a two sample-t-test for simplicity, even though the main statistical analysis 
may employ a statistically more powerful model-based approach. The estimates used for the 
mean and standard deviation of the changes from baseline to day 90 are taken from the literature 
as well as company pilot study data. In the pilot study, the mean change in mRS score from 
baseline to week 9 in the treatment group was -2.5 (SD=0.66) versus -1.3 (SD=0.46) in the sham 
group. In the literature a difference of 0.06 points on the mRS between treatment groups is 
considered clinically meaningful (114). As powering the trial to detect this difference would 
yield infeasibly large sample sizes, sample size projections were based on detecting a difference 
as low as 40% of the difference seen in the pilot trial = 0.5-point. To detect a 0.5-point difference 
between the groups with 80% power at a 5% level of significance using a standard deviation of 1 
point and 1:1 allocation ratio, the calculated sample size (PROC POWER in SAS V9.4) is 128 
participants in total, 64 participants in each arm. Allowing for a 15% dropout, 150 participants 
should be randomized. 
9.3 
POPULATIONS FOR ANALYSES 
The following analysis sets are defined for this study: 
− Intent-To-Treat (ITT) Analysis Set – will consist of all subjects randomized. In 
accordance with the ITT principle, all subjects randomized will be kept in their originally 
assigned treatment group. 
− Modified ITT Analysis Set (mITT) – will consist of all subjects from ITT analysis set for 
whom treatment was initiated and will be analyzed as randomized. 
− Per-Protocol Analysis Set (PP) – includes all subjects from the mITT analysis set who 
have no significant protocol deviations (examples of such potential protocol deviations 
are listed in § 7.2), were treated for a minimum of 20 completed sessions, with data 
available for the analysis (defined as at least one data point post baseline) and will be 
analyzed as treated. 
− Safety Analysis Set (SAF) - will consist of all subjects where treatment was initiated, 
with subjects analyzed as treated.  
The SAF analysis set will serve as the principal analysis set for the analysis of safety. 

 
 
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The mITT analysis set will serve as the principal analysis set for efficacy assessments (including 
for secondary endpoints). 
Efficacy assessments (including for secondary endpoints) will also be performed on the PP as 
well as the ITT analysis set as a sensitivity analysis. 
9.4 
STATISTICAL ANALYSES 
9.4.1 GENERAL APPROACH 
Statistical analyses will be performed using SAS® v9.4 or higher (SAS Institute, Cary, NC, 
USA). Statistical analyses and reporting will be performed in compliance with FDA Guidance 
E6 and E9 and ISO 14155;2020. 
Study data will be summarized with descriptive statistics and presented in tables and figures. 
Continuous variables will be summarized by a mean, standard deviation, minimum, median, and 
maximum and categorical variables by a count and percentage. For comparison of continuous 
variables, the two-sample t-test or the Wilcoxon rank sum test will be used as appropriate. For 
comparison of proportions (categorical variables), the chi-squared test or Fisher’s exact test will 
be used as appropriate. A Cochran-Armitage trend test may be used when the response is ranked. 
For comparison of time to event data, the log-rank test will be used. If multiple measurements 
are taken in a single subject, statistics described below will be appropriately modified to 
accommodate the within subject correlation.  
Detailed methodologies of the statistical analyses of the data collected in this study will be 
outlined in a trial-specific Statistical Analysis Plan (SAP). Any changes to planned analyses will 
be described and justified in the SAP. Analyses outlined in the SAP take precedent over those 
defined in the protocol to the extent there are any conflicts between the two documents. 
Significance Levels and Type I Error 
The overall significance level for this study is 5% using two-tailed tests, except for the group by 
site interaction that will be tested at a significance level of 15%. 
The hierarchy (stepwise gatekeeper) approach will be adopted for the primary and secondary 
endpoints to control type I error due to multiple endpoint testing. 
The primary endpoint will be analyzed first and only if the null hypothesis is rejected at a 
5% level of significance or lower then we shall continue to test the secondary endpoints in a 
hierarchical manner. Nominal p-values will be reported, even if eventually due to the hierarchy 
the result is not considered statistically significant. 

 
 
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The hierarchical order of analysis of the secondary endpoint family will be: 
1. Lead secondary endpoint: FMA-UE (upper limb motor impairment) – change from 
baseline (4-21 days post-stroke) to 90 days post-stroke. 
2. BBT (upper extremity function) – change from baseline (4-21 days post-stroke) to 90 
days post-stroke. 
3. 10MWT (gait speed) – change from baseline (4-21 days post-stroke) to 90 days post-
stroke. 
4. SIS Hand Domain (patient-reported hand function) – change from baseline (4-21 days 
post-stroke) to 90 days post-stroke. 
5. SIS-16 (patient-reported physical functional limitation) – change from baseline (4-21 
days post-stroke) to 90 days post-stroke. 
6. EQ-5D-5L (health-related quality of life) at 90 days post-stroke. 
9.4.2 ANALYSIS OF THE PRIMARY ENDPOINT 
The primary endpoint, mRS change from baseline (day 4-21 post-stroke) to 90 days post-stroke, 
will be compared between the treatment groups using repeated measures analysis of covariance 
(ANCOVA, SAS® MIXED procedure). 
The model will include the following fixed effects: treatment group, visit [categorical – midterm 
follow-up visit (± 4 days from 20th treatment) and Day 90 follow-up visit (day 90 ± 15 days 
post-stroke)], treatment group by visit interaction with baseline mRS and age entered as 
covariates. Age will be entered as a continuous variable so that the potential for co-linearity 
problems will be minimized. Center will be entered as a random effect. The treatment group by 
site interaction will be evaluated as well, but not as part of the principal statistical evaluation.  
The compound symmetry covariance structure will be used. If the model does not converge, then 
either the unstructured or autoregressive (AR1) (whichever model has the lower Akaike 
information criterion statistic) covariance matrix structure will be used instead. At this time point 
(up to 3 months post stroke), we do not expect a high proportion of dropouts, as a placebo effect 
of the sham treatment is expected and was taken into consideration in the design of the study. 
Thus, any missing data at this time point can be considered missing at random. Therefore, since 
likelihood based repeated measures is also an imputation method, for this evaluation no other 
method of imputation of missing data is considered beyond the model estimates. Nevertheless, 
should the missing at random assumption prove to be incorrect, a sensitivity analysis using 
methods for data imputation may be performed, such as last observed value (LOV) of that 
endpoint (115). The LOV is defined as the last available post baseline visit data up to and 
including the last treatment visit or termination visit. Additionally, we may consider multiple 

 
 
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imputation using a model incorporating key baseline prognostic features as well as the last post-
randomization if deemed necessary. 
The principal statistical analysis will be a comparison between the treatment groups, derived 
from the visit by treatment group interaction term from the model. The adjusted mean change 
from baseline in mRS scores at the 90 days post-stroke visit will be estimated from the model 
(LS Means) interaction term for each group as well as for the difference between the adjusted 
means and presented together with 95% confidence intervals and level of significance.  
The null hypothesis will be rejected in favor of the alternative hypothesis and the study deemed 
successful if the P value is <0.05 and the mean change mRS in the BQ 2.0 group is higher than 
that of the sham group at the 90 days post stroke visit. 
A shift analysis of the primary endpoint will be performed as a sensitivity analysis as well. 
Handling of Missing Primary Endpoint Data 
By the 90 days post-stroke visit, we do not expect a high proportion of dropouts, as a placebo 
effect of the sham treatment is expected and was taken into consideration in the design of the 
study by using conservative estimates of the treatment effect.  
All subjects with at least 1 post-baseline measurement will be included in the statistical analyses. 
The primary endpoint will be analyzed using a likelihood based repeated measures model, which 
can handle data missing at random.  
For the mITT set, missing primary outcome data at day 90 will be imputed with multiple 
imputation using a model incorporating key baseline prognostic features as well as the last post-
randomization observed value (LOV) of that endpoint (115). The LOV is defined as the last 
available post baseline visit data up to and including the last treatment visit or termination visit. 
The LOCF imputation method will also be used to carry forward the most recent data prior to 
withdrawal/dropout as a sensitivity analysis. 
9.4.3 ANALYSIS OF THE SECONDARY 
ENDPOINT(S) 
The hierarchy approach will be adopted for the primary and secondary endpoints to control type 
I error due to multiple endpoint testing. The order of the secondary endpoints in specified above 
in § 9.4.13. 
The change from baseline in FMA-UE, BBT, SIS Hand Domain, SIS-16 and 10MWT, and the 
EQ-5D-5L score at day 90, will be compared between the groups with analysis of variance 
adjusting for baseline value, if relevant (§ 9.4.2). 

 
 
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9.4.4 SAFETY ANALYSES 
Descriptive statistics will be presented per study group for all safety parameters. 
The primary safety variable, the cumulative incidence (and 95% CI) of adverse events (AEs) 
reported throughout the study in each of the study groups, will be presented in tabular format and 
will include incidence tables by severity and relationship to study device and/or procedure. 
Adverse event rates will be compared between the study groups with a Fisher’s exact test. 
Serious adverse events will be listed and discussed individually. 
Treatment tolerability will be presented. The number and percent of subjects who fail to 
complete the study and the number and percent of subjects who fail to complete the study 
because of adverse events will be presented. 
In addition, listings of all safety measures and device deficiencies will be produced. 
9.4.5 BASELINE DESCRIPTIVE STATISTICS 
Demographic and baseline condition related characteristics (such as measurements taken at 
screening) will be tabulated and compared between the study groups by data type. Continuous 
variables will be summarized by a mean, standard deviation, minimum, median, and maximum 
and categorical variables by a count and percentage. The statistical evaluation of baseline 
characteristics will include all available data from the ITT set. 
9.4.6 PLANNED INTERIM ANALYSES 
One interim analysis is planned, after 78 evaluable subjects will complete the study. 
Planning an interim analysis that permits an increase in the sample size as described below does 
not additionally inflate the type I error (116-119). In addition, the final analysis is performed 
using the conventional test as appropriate for the statistical hypothesis.  
Depending on the outcome of the interim analysis, the study will either continue to the originally 
planned sample size, stop for futility or continue with an increased sample size. These decisions 
will be made based on the conditional power (CP), which is defined as the conditional 
probability that the result will exceed a critical value at the interim given the observed effect 
size. 
Note that the interim analysis will be conducted on mITT analysis set. 

 
 
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After all the relevant data is entered into the database, and the database is cleaned, a soft lock to 
the database will be performed. An independent unblinded statistician (not the study statistician) 
will perform the assessments described. Only the unblinded statistician and members of the 
DSMB will be exposed to the interim report. The members of the data monitoring team of the 
Sponsor, if such a team is designated, will be limited to individuals with relevant expertise who 
are independent from the personnel involved in conducting or managing the trial. Only these 
members may have access to the unmasked information of the interim analysis. Investigators and 
Sponsor representatives will only be informed of the recommendation to continue or to 
discontinue the trial, or to implement other modifications in the trial procedure and design 
suggested by the DSMB, and based on the interim results. The unblinded statistician who is 
responsible for conducting the interim analyses should ensure that the unmasked data is not 
available to any unauthorized person within or outside the company. 
Decision Rules 
The study will either continue to the originally planned sample size if the result is “favorable”, 
stop for futility if the result is “unfavorable” or an increase will be made to the sample size if the 
result is “promising”. These decisions will be made based on the conditional power (CP), defined 
as the conditional probability that the result will exceed a critical value at the interim given the 
observed effect size 𝛿1̂ = difference between mean change from baseline mRS score for the BQ 
2.0 versus sham groups at the interim look.  
Notation: 
− n1= sample size at interim analysis. 
− n2= original sample size calculated based on assumed effect size. 
nmax = the highest sample size the company is willing to use, nmax = 292 subjects (344 
randomized including an allowance for a 15% dropout), and is based on a potential smaller effect 
size of ~0.33. 
CPmin = is the calculated minimum CP based on the ratios nmax/n2, n1/n2 and the target study 
power (80%). 
The following are the decision rules for the interim analysis which will be performed upon 
accrual of ~61% (n1/n2) of the originally planned sample size, ie, 78 evaluable subjects. These 
depend on the zone into which CP falls at the interim, the calculated CPmin, the maximum 
sample size designated for the study and the % of the originally planned sample size at which the 
interim analysis will be performed. Following this principle does not inflate the Type I error. 

 
 
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− If the result is “Unfavorable”, ie, CP < CPmin = 32.7375%, ie, interim result is so 
disappointing that it is not worth increasing the sample size to retrieve conditional power, 
stop the trial for futility. 
− If the result is “Promising”, ie, 32.7375% ≤ CP < 80% for the primary endpoint, the 
sample size is increased to recover the targeted power of 80%. The sample size used will 
be either the new calculated sample size based on the conditional power (117) or the 
predetermined maximum sample size of 292 (344 randomized including an allowance for 
a 15% dropout) subjects, whichever lower.  
− If the result is “Favorable”, ie, CP ≥ 80% for the primary endpoint, the interim results are 
sufficiently favorable and the trial continues to the original sample size planned of 128 
(150 randomized including an allowance for a 15% dropout) without the need to 
adaptively increase the sample size. 
Controlling the Alpha Level for the Primary Endpoint 
The overall alpha level for this study is 5%. Planning an interim analysis that permits an increase 
in the sample size as described above does not inflate the type I error (116, 118, 119), which 
means that the testing of the primary endpoint will be at a 5% level of significance. 
9.4.7 SUB-GROUP ANALYSES 
Subgroup analysis of the primary efficacy endpoint such as demographic or other baseline 
patient characteristics will be performed. Potential Sub-groups  
1. Sex 
2. Age groups (< 70 vs. ≥ 70 years) 
3. Race 
4. Ethnicity  
5. mRS 3 vs. 4 
6. FMA-UE score 
7. 10MWT score 
8. Received tPA/thrombectomy for the index stroke 
9. SAFE score at baseline (<5, 5-7, 8 or more) 
10. First stroke or not 
11. Right/left sided stroke 
12. Stroke mechanism 
13. Time from event to first treatment (< 14  days vs. ≥ 15 days) 

 
 
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14. Compliant vs. not-compliant50 
15. Treatment group assignment guess by the subject (blinding assessment) 
 
Pooling 
Subgroup analysis of the primary efficacy endpoint by site will be used to evaluate the 
poolability of the results. The significance of site-to-site variability in treatment effect will be 
evaluated by including site to the visit by group interaction term and will be added to the primary 
model. If the interaction time by site by group is found significant at a 15% level of significance, 
the reason for this will be further explored and rationalized. This evaluation may include 
demographic and baseline features, clinical and treatment history, and site comparability in the 
features found to be associated with the primary efficacy variable. 
9.4.8 TABULATION OF INDIVIDUAL 
PARTICIPANT DATA 
Listings of the efficacy and safety measurements will be provided. 
9.4.9 EXPLORATORY ANALYSES 
MoCA, ALDS and PHQ-8 scores at 90 days post stroke will be compared between the groups 
with analysis of variance adjusting for baseline value, if relevant (§ 9.4.2). The change from 
baseline to day 180 in mRS, SIS Hand Domain and EQ-5D-5L score at day 180, will be 
compared between the groups with analysis of variance adjusting for baseline value, if relevant. 
Safety through 180 days will also be summarized. Additionally, Bang’s blinding index will be 
assessed (120).  
Health economics data will be collected and analyzed for publication and other scientific 
purposes, but this is not intended to support regulatory submissions. 
Relationship between adherence to treatment as measured by the Qompass and the clinical 
outcomes will be explored. 
9.4.10 ADHERENCE AND RETENTION ANALYSES 
The numbers of subjects who were enrolled and completed each visit of the study will be 
provided, as well as the reasons for all enrollment discontinuations, grouped by major reason (eg, 
 
50 The compliance analysis will be conducted as an exploratory sensitivity analysis assessing the correlation of 
number of completed treatments with the primary efficacy endpoint. 

 
 
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lost to follow-up, adverse event, poor compliance). A list of discontinued patients, protocol 
deviations, and patients excluded from the efficacy analysis will be provided as well. The effects 
of non-compliance, dropouts, and possible covariates such as age and sex will be assessed to 
determine the impact on the general applicability of results from this study. 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
10.1.1 INFORMED CONSENT PROCESS 
10.1.1.1 CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED 
TO PARTICIPANTS 
Consent forms describing in detail the study device, study procedures and risks are given to the 
participant and written documentation of informed consent is required prior to starting 
administration of the study device. 
IMPORTANT NOTE: If an Investigator uses the BQ 2.0 without obtaining informed consent, 
the Investigator shall report such use to the Sponsor and the reviewing IRB within 5 working 
days after the use occurs51. 
10.1.1.2 CONSENT PROCEDURES AND DOCUMENTATION 
The informed consent process will comply with 21 CFR Part 50 and the recommendations set 
out in INTEGRATED ADDENDUM TO ICH E6(R1): GUIDELINE FOR GOOD CLINICAL 
PRACTICE E6(R2) (§ 4.8 -- Informed Consent of Trial Subjects). A copy of the full guidelines 
may be found on the ICH website52. The U.S. FDA draft guidance Informed Consent 
Information Sheet Guidance for IRBs, Clinical Investigators, and Sponsors (July 2014) will be 
followed. 
In obtaining and documenting informed consent, the Investigator will comply with the applicable 
regulatory requirement(s) and will adhere to GCP and to the ethical principles that have their 
origin in the Declaration of Helsinki, adopted by the 18th World Medical Assembly in Helsinki, 
Finland, in 1964, as last amended by the World Medical Assembly. 
Prior to the beginning of the trial, the Investigator must have the IRB (and, where applicable 
regulatory authority) written approval/favorable opinion of the written informed consent form 
 
51 21 CFR 812.150(a)(5) 
52 https://database.ich.org/sites/default/files/E6_R2_Addendum.pdf 

 
 
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(ICF) and any other written information to be provided to subjects. The Sponsor will supply a 
proposed ICF, which complies with regulatory requirements and is considered appropriate for 
the study. Any changes to the proposed consent form suggested by the Investigator must be 
agreed to by the Sponsor before submission to the IRB and local regulatory authority (if 
applicable) and a copy of the approved version must be provided to the Sponsor after IRB 
approval 
Neither the Investigator, nor the trial staff, should coerce or unduly influence a subject to 
participate or to continue to participate in a trial.  
The Investigator, or a person designated by the Investigator, must fully inform the subject or, if 
the subject is unable to provide informed consent, the subject's legally acceptable representative, 
of all pertinent aspects of the trial including the written information given approval/favorable 
opinion by the IRB. 
Before informed consent may be obtained, the Investigator, or a person designated by the 
Investigator, must provide the subject or the subject's legally acceptable representative ample 
time and opportunity to inquire about details of the trial and to decide whether or not to 
participate in the trial. All questions about the trial must be answered to the satisfaction of the 
subject or the subject's legally acceptable representative. The Investigator or his/her designee 
should also stress that the subject is completely free to refuse to take part or withdraw from the 
trial at any time. Prior to a subject’s participation in the trial, the written ICF must be signed and 
personally dated by the subject or by the subject's legally acceptable representative, and by the 
person who conducted the informed consent discussion. 
If a subject is unable to read or if a legally acceptable representative is unable to read, an 
impartial witness must be present during the entire informed consent discussion. After the 
written ICF and any other written information to be provided to subjects is read and explained to 
the subject or the subject’s legally acceptable representative, and after the subject or the subject’s 
legally acceptable representative has orally consented to the subject’s participation in the trial, 
and, if capable of doing so, has signed and personally dated the ICF, the witness must sign and 
personally date the consent form. By signing the consent form, the witness attests that the 
information in the consent form and any other written information was accurately explained to, 
and apparently understood by, the subject or the subject's legally acceptable representative, and 
that informed consent was freely given by the subject or the subject’s legally acceptable 
representative. 
Prior to participation in the trial, the subject or the subject's legally acceptable representative 
must receive a copy of the signed and dated written ICF and any other written information 
provided to the subjects. 

 
 
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During a subject’s participation in the trial, the subject or the subject’s legally acceptable 
representative must receive a copy of the signed and dated consent form updates and a copy of 
any amendments to the written information provided to subjects. 
With the subject’s prior consent, the subject’s general practitioner may also be informed that 
they are taking part in the trial. An electronic general practitioner letter template may be 
provided for this purpose. 
The written ICF and any other written information to be provided to subjects will be revised 
whenever important new information becomes available that may be relevant to the subject’s 
consent. Any revised written ICF, and written information must receive the IRB/EC (and, where 
applicable regulatory authority) approval/favorable opinion in advance of use. The subject or the 
subject’s legally acceptable representative must be informed in a timely manner if new 
information becomes available that may be relevant to the subject’s willingness to continue 
participation in the trial. The communication of this information should be documented. If 
relevant, all affected subjects shall be asked to confirm their continuing informed consent in 
writing. 
10.1.2 STUDY DISCONTINUATION AND CLOSURE 
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause. Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending or terminating party to study participants, 
Investigator(s), Sponsor and regulatory authorities, where applicable. If the study is prematurely 
terminated or suspended, the Investigator will promptly inform study participants, IRB/EC, and 
Sponsor, and will provide the reason(s) for the termination or suspension. Study participants will 
be contacted, as applicable, and be informed of changes to study Visits schedule. 
Circumstances that may warrant termination or suspension include, but are not limited to: 
− Determination of unexpected, significant, or unacceptable risk to participants; 
− Determination of possible serious health threat; 
− Demonstration of efficacy that would warrant stopping; 
− Insufficient compliance to protocol requirements and/or good clinical practice and/or 
regulatory requirements; 
− Data that are not sufficiently complete and/or evaluable; 
− Insufficient study enrollment; 
− Investigational product supply or manufacturing issues; 
− The Sponsor’s decision to modify or discontinue product development; 
− A request to discontinue the study by a regulatory or health authority. 

 
 
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Study-wide administration of study device will be halted if Grade ≥ 4 AEs determined to have 
“probable” or “causal” relationship are reported to the Sponsor. The Sponsor will notify the 
Investigators immediately when the event is reported, and enrollment screens will stop accepting 
new study participants. Where required, the Sponsor will inform the regulatory authorities of the 
temporary halt and the disposition of the study. 
Similarly, if suspicion of an unacceptable risk, including serious health threat, to subjects arises 
during the trial, or when so instructed by the IRB/EC or regulatory authorities, the Sponsor shall 
suspend the clinical investigation while the risk is assessed. The Sponsor shall terminate the 
clinical investigation if an unacceptable risk which cannot be mitigated is confirmed53. 
DSMB will be established in the study (refer to § 10.1.6 for details), and the Sponsor will inform 
the DSMB members within 24 hours of this occurrence and will provide the DSMB with AE 
listing reports. The DSMB will convene an ad hoc meeting by teleconference or in writing as 
soon as possible and will provide recommendations for proceeding with the study to the study 
Sponsor. 
Study may resume once concerns about safety, protocol compliance, and data quality are 
addressed, and satisfy the sponsor, IRB/EC and/or regulatory authority(ies). 
When a study is prematurely terminated, refer to § 7 for handling of enrolled study participants 
10.1.3 CONFIDENTIALITY AND PRIVACY  
Subject confidentiality is strictly held in trust by the participating Investigators, their staff, and 
the Sponsor and its agents. This confidentiality is extended to cover testing of biological samples 
in addition to the clinical information relating to participants. Therefore, the study protocol, 
documentation, data, and all other information generated will be held in strict confidence and 
stored in accordance with the applicable local laws and/or regulations.  
In compliance with guidelines regarding the monitoring of clinical studies and in fulfillment of 
the Investigator’s obligation to the Sponsor, it is required that he/she permit the Sponsor’s study 
Monitor and/or applicable regulatory authority representative to review that portion of the 
subject’s medical record that is directly related to the study. This shall include all study relevant 
documentation (including medical history to verify eligibility, laboratory tests results to verify 
transcription accuracy, treatment and diagnostic reports, admission/discharge summaries for 
hospital admissions occurring while the subject is on study and autopsy reports for deaths 
occurring during or in temporal proximity to the study). 
 
53 § 7.4.4 and 8.2.1 of ISO 14155:2020 

 
 
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As part of the required content of informed consent, the subjects must be informed that their 
records will be reviewed by the study Monitors or representatives of regulatory authorities. The 
subjects will also be informed that representatives of the DSMB may inspect their medical 
records to verify the information collected, and that all personal information made available for 
inspection will be handled in strictest confidence and in accordance with local data protection 
laws. 
Should access to the medical record require a separate waiver or authorization, it is the 
Investigator’s responsibility to obtain such permission from the subject in writing before the 
subject is entered into the study. 
All information provided to the Investigator by the Sponsor, including nonclinical data, 
protocols, CRFs, and verbal and written information, will be kept strictly confidential and 
confined to the clinical personnel involved in conducting this study, and no disclosure shall be 
made except in accordance with any right of publication granted to the Investigator. 
The study Monitor may inspect all documents and records required to be maintained by the 
Investigator, including but not limited to, medical records (office, clinic or hospital) and 
pharmacy records for the subjects in this study. The clinical study site will permit access to such 
records.  
Throughout this study, the subject data will only be linked to the Sponsor's clinical study 
database or documentation framework via a unique identification number. As permitted by all 
applicable laws and regulations, limited subject attributes, such as sex, date of birth (to the extent 
permitted) and/or age, and subject initials (where permitted) may be used to verify the subject 
and accuracy of the subject’s unique identification number. If the subject’s name appears on any 
documents (eg, laboratory analysis report) it must be obliterated before a copy of the document is 
supplied to the Sponsor for data management or other purposes. Medical information may be 
provided to the participant’s general practitioner or other appropriate medical personnel 
responsible for the subject's welfare. The subject’s contact information will be securely stored at 
each clinical site for internal use during the study. 
Trial findings stored on computer will be stored in accordance with local data protection laws. 
The Sponsor and any of its designees will maintain the confidentiality of all subject data and will 
not disclose information by which subjects may be identified to any third party, other than those 
directly involved in the treatment of the subject’s condition. If the results are published, the 
subject’s identity will remain confidential. 
At the end of the study, all records will continue to be kept in a secure location for as long a 
period as detailed in § 10.1.9.2. Subject’s research data, collected for purposes of statistical 
analysis and scientific reporting, will be transmitted to and stored by the Sponsor. This will not 

 
 
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include the subject’s contact or identifying information. Rather, individual subjects and their 
research data will be identified by a unique identification number. The study data entry and study 
management systems used by clinical sites and by the Sponsor’s research staff will be secured 
and password protected. 
10.1.4 FUTURE USE OF STORED SPECIMENS AND 
DATA  
Data collected for this study will be analyzed and stored either in the computers of the EDC 
system provider (refer to § 10.1.9.1 for details). In the event that a paper CRF replaces, 
temporarily or permanently, the electronic version, data collected using paper forms will be 
stored at the Sponsor’s premises. After the study is completed, the de-identified, archived data 
will be transmitted to and stored at the Sponsor’s premises, under the supervision of the Sponsor, 
for use by other researchers including those outside of the study. Permission to transmit the data 
to and store it at the Sponsor’s premises will be included in the informed consent. When the 
study is completed, access to study data will be provided through and by the Sponsor. 
Collection of biological samples is not planned in this protocol. 
10.1.5 KEY ROLES AND STUDY GOVERNANCE 
A list of the study Investigators and participating sites will be provided for inclusion in the trial 
master file and updates to the list will be provided during the trial. 
Study Steering Committee (SSC) will be established and the study and will operate in 
accordance with a trial-specific charter. List of members of the SSC will be provided for 
inclusion in the trial master file and updates to the list will be provided during the trial. Its non-
independent members may include the study Coordinating Investigator and may also include 
clinical collaborators and other identified collaborators, and the trial co-coordinators. The 
Sponsor and the study statistician will be allowed to attend the meetings but will have no voting 
status. Investigators and key trial personnel may be invited to join the SSC as appropriate to 
ensure representation from a range of centers and professional groups. 
Notwithstanding the obligations of the Sponsor and the Coordinating Investigator assigned for 
this study, the SSC will be responsible for the overall governance of the trial and will meet by 
teleconference or in-person as required. The Sponsor will be responsible for administration of the 
study and for updating the SSC and Investigators and for the exchange of information between 
the Investigators and members of the SSC. 

 
 
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10.1.6 SAFETY OVERSIGHT 
DSMB will be established to oversee the safety and efficacy of the trial. This board will be 
assembled according to GCP. List of members of the DSMB will be provided for inclusion in the 
trial master file and updates to the list will be provided during the trial. 
Data analyses will be supplied, in confidence, to the DSMB, which will be asked to give advice 
on whether the accumulated data from the trial, together with the results from other relevant 
research, justifies the continuing recruitment of further subjects. The DSMB will operate in 
accordance with a trial-specific charter based upon the template created by the Damocles Group 
(121). Members of the DSMB will be the only individuals who see the confidential, 
accumulating data from the trial; however, the Sponsor may receive subsets of the report, as seen 
fit by the DSMB (eg, accrual, compliance, data completeness). The board will meet as frequently 
as considered necessary, but at least semiannually, either in person or by teleconference.  
The DSMB may consider recommending stopping the trial early if:  
− the recruitment rate or data quality are unacceptable; 
− there are cases of excessive safety concern that compromise subject safety; or 
− results of any interim analysis indicate futility. 
The DSMB may also recommend continuation beyond the planned number of subjects in the trial 
if it is felt that further information might be of interest. If this is recommended, it will be 
submitted as an amendment, for approval of the applicable IRBs prior to implementation. 
Following each meeting, the DSMB will report their findings and recommendations to the 
Sponsor, or the SSC, should the latter be established in the study (see § 10.1.5 for details). No 
results relating to the trial will be made available to participants until the Sponsor (or the SSC, if 
established) considers the data sufficiently mature to justify such a course of action.  
DSMB may recommend to the Sponsor or the SSC to suspend recruitment in the event of serious 
or persistent non-compliance and/or very poor recruitment. 
10.1.7 CLINICAL MONITORING 
Participating sites will be monitored to confirm compliance with the protocol, and the protection 
of subjects’ rights. 
The Monitor will assess the source data and the data collected in the CRF to assure collected data 
integrity and quality, and will execute proper data governance measures to ensure compliance of 
the study records with the essential principles of data management throughout the study 

 
 
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lifecycle, ie, the data are attributable, legible, contemporaneous, original, accurate, complete, 
consistent, enduring, and available. 
Any major problems identified during monitoring may be reported to the Sponsor and the 
relevant regulatory bodies. This includes reporting serious breaches of GCP and/or the study 
protocol to the local IRB. 
Details of clinical site monitoring will be documented in a Clinical Monitoring Plan (CMP). The 
CMP describes in detail who will conduct the monitoring, at what frequency monitoring will be 
done, at what level of detail monitoring will be performed, and the distribution of monitoring 
reports. 
Independent audits may be conducted to ensure monitoring practices are performed consistently 
across all participating sites and that monitors are following the CMP. 
NOTE: audits may also occur after close-out activities have been completed at the site. 
10.1.8 QUALITY ASSURANCE AND QUALITY 
CONTROL 
Quality control (QC) procedures will be implemented beginning with the data entry system and 
data QC checks that will be run on the database will be generated. Any missing data or data 
anomalies will be communicated to the site(s) for clarification/resolution. 
Following written SOPs, the Monitors will verify that the clinical trial is conducted, and data are 
generated, documented (recorded), and reported in compliance with the protocol, GCP, and the 
applicable regulatory requirements (eg, Good Laboratory Practices (GLP), Good Manufacturing 
Practices (GMP)). Data governance measures to ensure compliance of the study records with the 
essential principles of data management throughout the study lifecycle (ie, the data are 
attributable, legible, contemporaneous, original, accurate, complete, consistent, enduring, and 
available) will include review of source documents by the Monitors. 
For more details on data collection and management and study data monitoring please refer to 
§§ 10.1.9 and 10.1.7, respectively. 
The investigational device will be used in strict adherence to the IFU provided by the Sponsor 
and only by trained operators (clinic operators or caregivers) certified by the Sponsor. 
10.1.9 DATA HANDLING AND RECORD KEEPING 
10.1.9.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  

 
 
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Data collection is the responsibility of the clinical trial staff at the site under the supervision of 
the site Investigator. The Investigator is responsible for ensuring the accuracy, completeness, 
legibility, and timeliness of the data reported. All source documents should be completed in a 
neat, legible manner to ensure accurate interpretation of data. Entries must be made in pen, using 
black or blue ink, to ensure clarity of reproduced copies, and must be legible. Any errors must be 
crossed out with a single stroke, the correction inserted and the change initialed and dated by the 
Investigator or his/her designee, to maintain audit trail. If it is not clear why a change has been 
made, an explanation must be written next to the change. Typing correction fluid must not be 
used. When making changes or corrections, cross out the original entry with a single line, and 
initial and date the change. Erasing, overwriting, or use of correction fluid or tape on the original 
are strictly forbidden. 
Clinical data (including AEs, concomitant medications) and clinical laboratory data for this study 
will be recorded using an electronic CRF (eCRF) solution, in accordance with U.S. Code of 
Federal Regulations; Electronic Records; Electronic Signatures (21 CFR Part 11) and EU Annex 
11 Computerised Systems, to enable clinical investigation data to be systematically captured, 
reviewed, managed, stored, analyzed and reported. Investigators and their designees will be 
provided comprehensive training in the eCRF data collection instruments, by the Sponsor, during 
the Study Initiation Visit and, if required, later in the trial. Investigators must review and 
electronically sign the completed eCRF for each study participant.  
Hardcopies of the study Visit worksheets may be provided for use as source document 
worksheets for recording data for each participant enrolled in the study.  
All copies of the retained original source documents shall be certified54. 
Transcription of data from paper or electronic sources to the eCRF 
Data elements can be transcribed into the eCRF from paper or electronic source documents, 
other than hardcopy of the eCRF serving as source documents worksheet. For these data 
elements, the electronic or paper documents from which the data elements are transcribed are the 
source. These data must be retained by the Investigators and made available for inspection by the 
study Monitors and/or that of regulatory authorities, if requested (eg, an original or certified copy 
of a laboratory report, instrument printout, progress notes of the Investigator, the study 
participant’s hospital chart(s), nurses’ notes, patient/subject questionnaires). 
 
54 A certified copy is a copy (irrespective of the type of media used) of the original record that has been verified, (ie, 
by a dated signature or by generation through a validated process), to have the same information including data that 
describe the context, content, and structure, as the original (§ 3.7 of ISO 14155:2020) 

 
 
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Data to be collected in case of termination or withdrawal 
Whenever participation of a subject is terminated, or subject withdraws from the study:  
a. all eCRFs, including follow-up, must be completed, regardless of treatment received, 
up to the point of withdrawal or termination. 
b. all data collected up to the point of withdrawal or termination will be maintained in 
the database and included in subsequent analyses. 
c. information obtainable from public records (eg, death) does not require consent. This 
information may be recorded on the appropriate eCRF. 
Responsibilities 
The eCRFs must be completed, signed and dated by the Investigator or his/her designee (as 
delegated on the Study Responsibilities Form/Delegation Log) within the time frame listed 
below (Table 5). The Investigator will be responsible for the timing, completeness, and accuracy 
of the subjects’ CRF/eCRFs. 
Table 5. Summary of CRF/eCRF forms completion time frame 
eCRF 
Schedule for CRF/eCRF completion 
Screening visit 
Within 1 day of completion. 
Study Procedure 
Within 5 days of completion. 
Study Follow-up 
Within 5 days of completion. 
Safety events 
Refer to §§ 8.3.5 and 8.3.6 
Concomitant medications 
Within 5 days of completion of relevant investigational product use. 
Study Termination 
Within 5 days of termination. 
Data management will be the responsibility of the Sponsor. The eCRFs will be checked for 
missing or unusual values (range checks), timing, and for consistency over time, both manually 
and by integrated database validation checks. The data may also be periodically queried by the 
trial statistician. If any problems are identified during in-house monitoring, a clarification request 
specifying the problem will be sent to the site Investigator. this will be done via the EDC system, 
however, if access to the EDC system is not possible, temporarily or permanently, a data 
clarification form (DCF) will be sent to the site. The correct data should be written on the DCF 
and signed by a responsible person at the site (as assigned on the site’s Study Responsibilities 
Form/Delegation Log. All trial data will be entered and stored in the trial database. Queries, 
whether electronic or paper, must be answered within 15 business days of receipt. 
Data recorded in the eCRF should be derived from source documents and be consistent with the 
data recorded on the source documents or certified copies of the latter, where source documents 
are not available in the ISF. Any discrepancies between the eCRF and source documents from 

 
 
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which the eCRF was derived should be explained and captured in a progress note and maintained 
in the participant’s official electronic study record. Clinical data will be transcribed directly from 
the source documents. The authorized person transcribing the data from the source documents is 
regarded as the data originator. 
Data originators 
A list of all authorized data originators will be maintained by the CRO (Syntactx-NAMSA) and 
made available at each clinical site. 
Identification of data originators relies on identification (log-on) codes and unique passwords 
and it is the responsibility of the data originators to maintain the security and integrity of the 
authorized usernames and passwords.  
The CRO (Syntactx-NAMSA)will keep a list of the individuals with authorized access to the 
eCRF. Only those individuals who have documented training and authorization will have access 
to the eCRF data and will be assigned their own identification (log-on) codes and passwords. 
eCRF data entry 
The eCRF will include an audit report to record who entered or generated the data and when it 
was entered or generated. Changes to the data will not obscure the original entry, and a record 
who made the change, when, and why will be maintained. 
The audit trail of the eCRF data will be readily available in a human readable form and will 
provide information that will allow reconstruction and evaluation of the clinical investigation. In 
the event of temporary or permanent substitution of eCRF with its paper counterpart, the audit 
trail of the latter will be established and maintained as detailed earlier in this section for the audit 
trail of the source documents. 
Only the Investigators and their designees will perform modifications or corrections to the eCRF 
data. 
The eCRF will feature password protection and employ electronic prompts, flags, and data 
quality checks, such as automatic range checks, to identify data that appear inconsistent, 
incomplete, or inaccurate and minimize errors and omissions during data entry. Prompts will 
alert the data originator to missing data, inconsistencies, inadmissible values (eg, value or date 
out of range), and to request additional data where appropriate. 
No data identifying subjects by name will be entered into the central study database.  

 
 
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When data elements are transcribed from paper sources into the eCRF, the Investigators will also 
retain the paper sources, or certified copies, for the period defined in § 10.1.9.2, for regulatory 
review.  
eCRF substitution with paper CRF 
In the event that a paper CRF replaces, temporarily or permanently, the electronic version, the 
rules of completion of the source documents detailed above will apply to paper CRF. 
The completed original CRFs must be sent to the Sponsor, with a copy held by the Investigator 
in their ISF. CRFs completion guidelines must be followed when entering data into CRF. All 
sections are to be completed before returning the CRF to the Sponsor. 
Required regulatory documents 
It is the responsibility of the Investigator and study staff to maintain a comprehensive and 
centralized filing system of all study-related documentation, which is suitable for inspection at 
any time by the Sponsor, IRB and/or regulatory authority, based on the recommendations 
published in Annex E of the ISO 14155 standard and § 8 of the ICH GCP E6(R2) guideline. 
Investigator/Institution should maintain a record of the location(s) of their respective essential 
documents. The storage system (irrespective of the media used) should provide for document 
identification, version history, search and retrieval. Elements must include, among others: 
a. Patient files containing the source documentation and the informed consent. 
b. Investigator files, containing device accountability records, or dispensation logs, 
where applicable, and all related correspondence.  
c. Confidential disclosure agreement with the Sponsor. 
d. Investigator files, containing all study related correspondence. 
e. Protocol with all amendments 
f. Copies of all pre-study documentation and all correspondence to and from the IRB 
and/or regulatory authority and the Sponsor or Sponsor representatives. 
g. Up-to-date version of IB, where applicable. 
h. Insurance certificate(s). 
i. Up to date (within the past two years) curriculum vitae for the Investigators. 
j. Signed and dated Investigator and Site agreement. 
k. Assurance that the reviewing IRB complies with the regulatory requirements set forth 
in U.S. Code of Federal Regulations; Institutional Review Boards (21 CFR 56) and/or 
an equivalent local regulation. The required documentation will consist of the name 
and address of the IRB and a list of its members, including their titles, occupations, 
and any institutional affiliations. 

 
 
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l. A copy of the formal written notification to the Investigator regarding approval of the 
protocol by the IRB (and, where applicable, regulatory authority). 
m. A copy of the IRB (and, where applicable, regulatory authority) approved ICF and 
other adjunctive materials (eg, advertising) to be used in the study, including written 
documentation of IRB approval of these items. 
A guideline on the content, management and archiving of the clinical trial master file (paper 
and/or electronic) acceptable for the purposes of this study is available from the European 
Medicines Agency55. 
10.1.9.2 STUDY RECORDS RETENTION  
It is the responsibility of the Investigator to ensure that all essential trial documentation and 
source records (eg, signed ICFs, ISFs including all approval letters, pharmacy files, device 
accountability logs, subjects’ hospital notes, copies of CRFs, etc.) are kept after the trial has 
ended. Investigators shall maintain the records during the investigation and for a period of 2 
years after the latter of the following two dates: the date on which the investigation is terminated 
or completed, or the date of notice from the Sponsor that the records are no longer required for 
purposes of supporting a premarket approval application, a notice of completion of a product 
development protocol, a humanitarian device exemption application, a premarket notification 
submission, or a request for De Novo classification. These documents should be retained for a 
longer period, however, if required by local regulations56. 
The Sponsor will notify Investigators when retention of study records is no longer required. No 
records will be destroyed without the written consent of the Sponsor. Study records must be 
stored in a safe and secure location permitting timely retrieval, if necessary. Study records that 
must be retained include CRFs, signed ICFs, correspondence with the IRB, study device 
dispensing and inventory records, source documents and screening/enrollment logs. 
Should the Investigator relocate or retire, the responsibility for maintaining the study records 
may be transferred to another Investigator. The Sponsor must be notified of the identity of the 
individual assuming responsibility for maintaining the study records and the location of their 
storage. If no other individual at the site is willing to assume this responsibility, the Sponsor will 
assume responsibility for maintaining the study records, provided this does not contradict local 
 
55 Good Clinical Practice Inspectors Working Group (GCP IWG) Guideline on the content, management and 
archiving of the clinical trial master file (paper and/or electronic) [06 December 2018 EMA/INS/GCP/856758/2018] 
https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-content-management-archiving-clinical-
trial-master-file-paper/electronic_en.pdf 
56 For instance, to comply with CHAPTER III(2) of ANNEX XV of the MDR 

 
 
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regulations. If applicable, notice of a transfer shall be given to the U.S. FDA not later than 10 
working days after transfer occurs57. 
10.1.10 
PROTOCOL DEVIATIONS  
A protocol deviation is any change, divergence, or departure from the study design or procedures 
defined in this clinical investigation protocol (CIP), whether intentional or unintentional, or GCP 
requirements. The noncompliance may be either on the part of the participant, the Investigator, 
or the study site staff. 
Important (or significant, major) protocol deviations58 are a subset of protocol deviations that 
may significantly impact the completeness, accuracy, and/or reliability of the study data or that 
may significantly affect a subject's rights, safety, or well-being59, such as:  
1. Departure from any protocol inclusion, exclusion, or randomization criterion 
2. Failure to promptly report a serious or unexpected AE 
3. Unsigned informed consent form 
4. BQ 2.0 device used outside protocol / IFU requirements (deviations related to Qompass 
usage will be considered as non-significant) 
5. Other ethical or clinical considerations at the discretion of Investigator 
6. Enrolment in another interventional study overlapping with the period of participation in 
this study 
As a result of deviations, corrective and preventive actions (CAPA) are to be developed as 
required.  Protocol deviations and site/investigator non-compliance will be closely monitored by 
the CRO and the sponsor.  
The sponsor reserves the right to suspend enrolment until site retraining occurs and site 
procedures are defined to prevent further violations. The sponsor also reserves the right to close a 
site from continued study participation should there be evidence of continued protocol non-
compliance. 
These practices are consistent with  
 
57 21 CFR 812.140(e) 
58 Protocol violation and important (significant) protocol deviation are sometimes used interchangeably to refer to a 
significant departure from protocol requirements. As the word “violation” may also have other meanings in a 
regulatory context, “violation” will not be used in this protocol in the context of instance(s) of failure to follow the 
requirements of the clinical investigation protocol. 
59 E3 Implementation Working Group ICH E3 Guideline: Structure and Content of Clinical Study Reports 
Questions & Answers (R1) 

 
 
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- 
the following chapters of the ICH Integrated Addendum to ICH E6(R1): Guideline for 
Good Clinical Practice E6(R2)60: 
a. 4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3 
b. 5.0 Quality Management, sections 5.0.2, 5.0.3, 5.0.4 
c. 5.1 Quality Assurance and Quality Control, section 5.1.1 
d. 5.20 Noncompliance, sections 5.20.1, and 5.20.2. 
- 
the following chapters of EN ISO 14155:2011 (and, in parentheses, ISO 14155:2020): 
a. 9.6 Compliance with the CIP (10.6) 
b. 8.1 Clinical Quality Assurance and Quality Control (9.1; Clinical Quality 
Management) 
Departures from the protocol may be permissible in a medical emergency, to protect the rights, 
safety and well-being of human subjects, at the discretion of the Investigator or other physician 
in attendance. In such an emergency, the Investigator should contact the Sponsor as soon as 
possible, but no later than within 24 hours of the event, to discuss the circumstances of the 
emergency. 
If possible, the Sponsor should be contacted before any deviation from the protocol is 
implemented. If the requested deviations may affect the scientific soundness of the plan or the 
rights, safety, or welfare of human subjects, approval from the FDA, if applicable, (and, where 
applicable, additional applicable regulatory authorities) and IRB will also be required61.  
If a protocol deviation was conducted by the site without getting a waiver first, the deviation 
should be recorded by the Monitor and signed by the Investigator. It is the responsibility of the 
Investigator to use continuous vigilance to identify and report deviations within 5 working days 
of identification of the protocol deviation, or within 5 working days of the scheduled protocol-
required activity. All deviations, and the reasons for deviations, must be addressed in study 
source documents, in the CRF, and must be reported to the Sponsor. 
Protocol deviations must be reported to the local IRB per their guidelines. The site 
Investigator/study staff are responsible for knowing and adhering to their IRB (and, where 
applicable, regulatory authority) requirements. 
 
60 https://database.ich.org/sites/default/files/E6_R2_Addendum.pdf 
61 21 CFR 812.150(a)(4) and 812.35(a) 

 
 
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10.1.11 
PUBLICATION AND DATA SHARING 
POLICY 
In accordance with any national regulations62, a description of the clinical investigation shall be 
registered in a publicly accessible database before recruitment of the first subject. When required 
by the national regulations, the content shall be updated throughout the conduct of the clinical 
investigation and the results entered at completion of the clinical investigation63. 
Access to data 
Being the Sponsor, BrainQ Technologies Ltd. will have exclusive ownership of the data and 
results. In cases where co-sponsorship agreement(s) is in force data ownership issues will follow 
the signed agreements with co-sponsors. Information obtained from this study may be disclosed 
to corporate partners and/or consultants of the Sponsor. 
Communication of the study results 
Methods and results of this trial may be submitted for publication in a peer-reviewed journal. A 
methods paper, an interim results paper and/or a primary results paper may be prepared 
according to the specific guidelines in the ‘EMAGINE’ trial publication policy document. 
Proposals for secondary papers or presentations must be approved as addressable with study data 
by majority vote of the voting Steering Committee members. The Steering Committee will 
establish a Writing Group and designate a Chair, selected from among the proposed authors, 
guided by site productivity in the trial, known expertise of authors, and past author productivity 
in the use of the EMAGINE dataset. Further details regarding secondary publications are 
specified in the ‘EMAGINE’ trial publication policy document. All manuscripts and abstracts to 
be presented at professional conferences must be reviewed and approved by the Steering 
Committee (by majority of voting members) prior to submission. In addition to approval by the 
Committee, BrainQ must review and approve manuscripts at least 30 days in advance of 
submission, and abstracts at least 7 days before submission. Additionally, posters and slide sets 
for presentation at national conferences must be submitted to the Chair of the Steering 
Committee and a BrainQ Steering Committee representative at least 7 days in advance of the 
presentation for review and approval. Authors must acknowledge that the trial was sponsored by 
BrainQ Technologies Ltd. Intellectual property rights belong to BrainQ Technologies Ltd. 
Authorship eligibility guidelines 
 
62 eg, 42 CFR Part 11 in the United States. 
63 § 5.4 of ISO 14155:2020. 

 
 
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Publication authorship will be based on the specific guidelines in the ‘EMAGINE’ trial 
publication policy document. Site enrollment total will determine whether PIs and any Co-PIs 
are included as authors, and the order in which they are listed. 
Public access to study documents 
The study protocol will be made available on a publicly accessible website. 
10.1.12 
CONFLICT OF INTEREST POLICY 
Financial and other competing interests, if any, of Investigator(s) will be disclosed in the ICF. 
Conflict of interests of study oversight group members (DSMB and/or SSC; if such are 
established in the study) will be disclosed and managed by the Sponsor. 
10.2 ADDITIONAL CONSIDERATIONS 
Not applicable. 
 
 

 
 
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10.3 ABBREVIATIONS 
 
ACH 
Acute Care Hospital 
ADL 
Activities of Daily Living 
AE 
Adverse Event 
AHA 
American Heart Association 
ALDS 
Academic Medical Center Linear Disability Scale 
ANOVA 
Analysis of Variance (will not be expanded) 
ARAT 
Action Research Arm Test 
BBB 
Basso, Beattie, and Bresnahan locomotor test 
BBT 
Box and Block Test 
CDISC 
Clinical Data Interchange Standards Consortium 
CE 
Conformité Européene (European Conformity; will not be expanded) 
CFR 
Code of Federal Regulations (will not be expanded) 
CI 
Confidence Interval (will not be expanded) 
CIMT 
Constraint-Induced Mobility Therapy 
CMP 
Clinical Monitoring Plan 
CNS 
Central Nervous System 
CONSORT Consolidated Standards of Reporting Trials 
COVID 
Coronavirus Disease (will not be expanded) 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CT 
Computed Tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DCF 
Data Clarification Form 
DSM 
Diagnostic and Statistical Manual of Mental Disorders 
DSMB 
Data and Safety Monitoring Board 
EC 
Ethics Committee; or European Commission (if followed by legislation number) 
eCRF 
electronic Case Report Form 
EDC 
Electronic Data Collection 
EEG 
Electroencephalography 
ELF 
Extremely Low Frequency 
EMF 
Electromagnetic Field 
EN 
European Norm (will not be expanded) 
EU 
European Union (will not be expanded) 
EVT 
Endovascular Thrombectomy 
FA 
Fractional Anisotropy 
FDA 
Food and Drug Administration 
FMA-LE 
Fugl-Meyer Assessment for Lower Extremity 
FMA-UE 
Fugl-Meyer Assessment for Upper Extremity 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation 
GMP 
Good Manufacturing Practices 
HDE 
Humanitarian Device Exemption 
HIPAA 
Health Insurance Portability and Accountability Act 

 
 
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HRQoL 
Health-Related Quality of Life 
IADL 
Instrumental Activities of Daily Living 
ICF 
Informed Consent Form 
ICU 
Intensive Care Unit 
ICH 
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for 
Human Use 
IEC 
International Electrotechnical Commission (will not be expanded) 
IFU 
Instructions for Use 
IRB 
Institutional Review Board 
IRF 
Inpatient Rehabilitation Facility 
IRT 
Interactive Response Technology 
ISF 
Investigator Site File 
ISO 
International Organization for Standardization 
ITT 
Intention to Treat 
IVT 
Intravenous Thrombolysis 
IWR 
Interactive Web-based Response 
MDR 
Medical Device Regulation 
mITT 
Modified Intention to Treat 
ML 
Machine Learning 
MoCA 
Montreal Cognitive Assessment 
MOP 
Manual of Procedures 
MRI 
Magnetic Resonance Imaging 
mRS 
modified Rankin Scale 
mRT 
modified Randomized as Treated 
NCI 
National Cancer Institute 
NIH 
National Institutes of Health 
NIHSS 
National Institutes of Health Stroke Scale 
NINDS 
National Institute of Neurological Disorders and Stroke 
NMES 
Neuromuscular Electrical Stimulation 
OT 
Occupational Therapy 
PHQ-9 
Patient Health Questionnaire-9 
PHQ-8 
Patient Health Questionnaire-8 
PT 
Physical Therapy 
QC 
Quality Control 
RCT 
Randomized Controlled Trial 
RFA-A 
Rankin Focused Assessment-Ambulatory 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SD 
Standard Deviation (will not be expanded) 
SIS 
Stroke Impact Scale 
SNF 
Skilled Nursing Facility 
SoA 
Schedule of Activities 
SOP 
Standard Operating Procedure 
SSC 
Study Steering Committee 
SW 
Software 
tMCAO 
temporary Middle Cerebral Artery Occlusion 

 
 
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UADE 
Unanticipated Adverse Device Effect 
USA or U.S. United States of America 
 
 

 
 
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10.4 PROTOCOL AMENDMENT HISTORY 
 
Revision 
Date 
Description of Change  
Brief Rationale 
1 
August 1, 
2021 
Modifications to statistical 
plan (such as slight increase of 
sample size and update of the 
interim analysis plan), as well 
as addition of a stratification to 
the randomization scheme and 
blindness quality assessment 
and analysis.  
Increase of 5% of dropout 
allowance due to feedback from 
clinicians. Some of the changes 
were a result of a sprint 
discussion with the FDA.  
 
 
Allowing randomization and 
treatments to be conducted in 
ACH, and an update in the 
SOA and visits names, 
accordingly.  
Potential subjects might miss the 
study enrollment window if 
discharged late from ACH (4-10 
days from stroke). The said 
change will allow to more eligible 
patients to be randomized within 
the said window. 
 
 
A focused, long-term outcome 
assessment on the 180th (±15) 
day after the stroke was added. 
This longer follow up will allow a 
better characterization of the 
long-term effect of the treatment  
 
 
Slight changes to the inclusion 
and exclusion criteria  
Mainly minor changes in order to 
simplify, reduce redundancy 
and/or operationalize the criteria.  
 
 
Endpoints forms added as 
appendix to this revision 
N/A 
2 
January 20, 
2022 
Updating the official title of 
the study to: EMAGINE Study 
EMAGINE is derived from 
electromagnetic field Ischemic 
Stroke - Novel Subacute 
Treatment. We believe that this 
name well reflects the shared 
dream and aspiration of many 
years of all study members to 
bring new and effective therapies 
to stroke patients. 
 
 
Extend window of recruitment 
from 4-10 days to 4-14 days  
Based on inputs from active sites 
and pre-screening data, the 
widening of the window for 
recruitment is intended to allow 
for more patients to be enrolled in 
the study, as well as to allow the 
sites more time to complete all 
screening activities. Scientifically, 

 
 
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this wider window is in line with 
the window of recruitment which 
was in established for the pilot 
study (BQ3).  
 
 
Adding a BQ 2.0 key 
component (Qompass 
adhesive) 
This component was designed to 
detect the electromagnetic field 
that the subject is exposed to, to 
ensure a subject receives the 
treatment as intended and allow 
for in depth monitoring and 
treatment optimization. During 
the study, the component will 
only collect data and the data will 
not be accessible to any blinded 
personnel or study participants in 
order to maintain the blind. 
 
 
Add an option for urine or 
blood pregnancy testing and 
reliance on test result available 
through medical records 
Potential female subjects might 
miss the study enrollment window 
due to laboratory processing time. 
The said change will allow more 
eligible patients to be randomized. 
 
 
Adding footnotes to Schedule 
of Assessments re Imaging 
Adding clarification with respect 
to imaging time point and the 
preferred image type. 
 
 
Add an exploratory endpoint 
for the Qompass 
To explore the relationship 
between adherence to treatment as 
measured by the Qompass and the 
clinical outcomes 
 
 
Reducing the number of initial 
in person sessions from 7 to 4 
Allow for more flexibility 
3 
June 01, 
2022 
Extend window of recruitment 
from 4-14 days to 4-21 days  
Based on inputs from active sites 
and pre-screening data, the 
widening of the window for 
recruitment is intended to allow 
for more patients to be enrolled in 
the study, as well as to allow the 
sites more time to complete all 
screening activities. Scientifically, 
this wider window is also in line 
with the window of recruitment 
which was used in the pilot study 
(BQ3).  
 
 
Change exclusion criteria #3 
from "Previous ischemic or 
Given that other inclusion and 
exclusion criteria require the 

 
 
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hemorrhagic stroke in the 3 
months before the index 
stroke." To "Previous ischemic 
or hemorrhagic stroke within 2 
weeks before the index stroke." 
prospective subjects to be 
medically stable and with a pre-
stroke mRS score of 0-1, 2 weeks 
are hypothesized to be sufficient 
time. This change will allow more 
patients to be enrolled into the 
study. 
 
 
Patient recruitment and 
treatment setting; change from 
ACH and IRF to ACH, IRF, 
SNF, outpatient or home 
setting 
Potential subjects may be enlisted 
and/or treated at each location, as 
long as they adhere to the overall 
inclusion-exclusion criteria. 
This change will allow more 
patients to be enrolled into the 
study. 
 
 
Change inclusion criteria #3 
from "Age 22 to 80 years of 
age (inclusive)." To "Age 22 to 
85 years of age (inclusive)." 
Considering the precautions taken 
via other inclusion and exclusion 
criteria (e.g., pre-mRS stroke of 
0-1, life expectancy of over 12 
months, etc.) which sets specific 
physical and health conditions 
thresholds on participation in the 
study, as well as supporting 
literature and Steering Committee 
recommendation, the age limit of 
85 was decided as a just balance 
to allow for more patients to be 
enrolled into the study. 
 
 
Removal of the examples 
provided in exclusion #5 (eg, 
hemianopia, diplopia, severe 
nystagmus, blindness) 
Removing the examples given to 
avoid confusion when assessing 
potential subjects. 
 
 
Reducing the number of initial 
in person sessions from 4 to 
none, and alternatively allow 
the operators the discretion to 
decide when are the subjects 
and caregivers ready to 
conduct sessions independently  
As different subjects and 
caregivers require different 
amount of training, the change 
will allow for more flexibility 
while keeping the initial rationale 
in place.  
 
 
Correction to the FMA-UE 
worksheet  
Addition of a clarification of 
subject physical starting position 
for items 19-22 which was 
omitted. 
 
 
Updates to the publications and 
data sharing policy 
Updates made to further match 
SPIRIT guidelines  

 
 
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F 
 

 
 
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12 APPENDICES 
 
12.1 APPENDIX 1 – QUESTIONNAIRES AND FUNCTIONAL TEST 
 

 
 
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