A Study to Assess Midline Frontal Theta (MFT) Power as Measured by Stimulus-locked Electroencephalography (EEG) Before and After AKL-T01 Treatment for Improving Attention in Pediatric Participants Ages 8-12 Years Old With Attention Deficit Hyperactivity Disorder (ADHD)
Phase: NA
Conditions: Attention Deficit Hyperactivity Disorder
Sponsor: Akili Interactive Labs, Inc.

i
A study to assess Midline Frontal Theta (MFT) power as 
measured by stimulus-locked electroencephalography (EEG) 
before and after AKL-T01 treatment for improving attention in 
pediatric participants ages 8-12 years old with Attention 
Deficit Hyperactivity Disorder (ADHD) 
Sponsor Protocol ID: 001S-C 
Sponsor: Akili Interactive Labs, Inc 
Principal Investigator: Elysa J. Marco, MD 
Version Number:  1.0 
February 8, 2019 
NCT03844269 

 
 
ii 
PROTOCOL APPROVAL PAGE 
 
Study Title: A study to assess Midline Frontal Theta (MFT) power as measured by stimulus-locked 
electroencephalography (EEG) before and after AKL-T01 treatment for improving attention in 
pediatric participants ages 8-12 years old with Attention Deficit Hyperactivity Disorder (ADHD) 
 
Version:  
 
1.0 
 
Date of Issue:   
February 8, 2019 
 
Study Sponsor:  
Akili Interactive, Inc. 
 
 
 
125 Broad St., 4th FL 
 
 
 
Boston, MA 02110 
 
 
We, the undersigned, have read and approve this protocol and agree on its content. 
 
 
 
 
 
_______________________________________  
_______________________________________ 
Elysa J. Marco, MD 
 
 
 
 
Anil Jina, MD 
Principal Investigator 
 
 
 
 
Sponsor – Medical Affairs 
 
 
 
 
 
 
 
_______________________________________  
_______________________________________ 
Scott Kellogg 
 
 
 
 
 
Joaquin A. Anguera, PhD 
Sponsor – Clinical Operations 
 
 
 
Assistant Professor – UCSF  
 
 
 
 
 
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iii 
Summary of Changes from Previous Version: 
 
Affected Section(s) 
Summary of Revisions Made 
Rationale 
 
 
 
 

  
 
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Table of Contents 
STATEMENT OF COMPLIANCE ............................................................................................................................. 1 
1 
List of Abbreviations ....................................................................................................................................... 2 
1 
PROTOCOL SUMMARY ............................................................................................................................... 3 
1.1 
Synopsis ................................................................................................................................................ 3 
1.2 
Schema .................................................................................................................................................. 4 
1.3 
Schedule of Activities (SoA) ............................................................................................................... 5 
2 
INTRODUCTION ............................................................................................................................................ 5 
2.1 
Study Rationale .................................................................................................................................... 5 
2.2 
Background ........................................................................................................................................... 6 
2.3 
Risk/Benefit Assessment .................................................................................................................... 6 
2.3.1 
Known Potential Risks ..................................................................................................... 6 
2.3.2 
Known Potential Benefits ................................................................................................ 7 
2.3.3 
Assessment of Potential Risks and Benefits ............................................................... 7 
3 
OBJECTIVES AND ENDPOINTS ................................................................................................................ 7 
4 
STUDY DESIGN ............................................................................................................................................. 7 
4.1 
Overall Design ...................................................................................................................................... 7 
4.2 
Justification for Dose ........................................................................................................................... 8 
5 
STUDY POPULATION ................................................................................................................................... 8 
5.1 
Inclusion Criteria................................................................................................................................... 8 
5.2 
Exclusion Criteria ................................................................................................................................. 9 
6 
STUDY INTERVENTION ............................................................................................................................... 9 
6.1 
Study Intervention ................................................................................................................................ 9 
6.1.1 
Study Intervention Description ....................................................................................... 9 
6.1.2 
Study Intervention Compliance .................................................................................... 10 
6.2 
Concomitant Medication and Treatment ........................................................................................ 10 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL .................................................................................................................... 10 
7.1 
Discontinuation of Study Intervention ............................................................................................. 10 
7.1.1 
Participant Discontinuation or Withdrawal .................................................................. 10 
7.1.2 
Lost to Follow-Up ........................................................................................................... 11 
8 
STUDY ASSESSMENTS AND PROCEDURES...................................................................................... 11 
8.1 
Eligibility and Efficacy Assessments ............................................................................................... 11 
8.2 
Safety and Other Assessments ....................................................................................................... 12 
8.3 
Adverse Events and Serious Adverse Events ............................................................................... 12 
8.3.1 
Definition of Adverse device effects (AdE) ................................................................. 12 
8.3.2 
Definition of unanticipated Adverse device effects (uade) ...................................... 12 
8.3.3 
previously known adverse device effects ................................................................... 13 
8.3.4 
Classification of an Adverse Event .............................................................................. 13 
8.3.5 
Time Period and Frequency for Event Assessment and Follow-Up ...................... 14 
8.3.6 
Adverse event Reporting............................................................................................... 14 
8.4 
Unanticipated Problems .................................................................................................................... 14 
8.4.1 
Definition of Unanticipated Problems (UP)................................................................. 14 
8.4.2 
Unanticipated Problem Reporting ................................................................................ 15 
9 
STATISTICAL CONSIDERATIONS ........................................................................................................... 16 
9.1 
Statistical Hypotheses ....................................................................................................................... 16 
9.2 
Populations for Analyses .................................................................................................................. 16 

  
 
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9.3 
Statistical Analyses ............................................................................................................................ 16 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .............................. 16 
10.1 
Confidentiality and Privacy ............................................................................................................... 17 
10.2 
Data Handling and Record Keeping ............................................................................................... 17 
10.2.1 
Data Collection and Management Responsibilities .................................................. 17 
10.2.2 
Study Records Retention .............................................................................................. 17 
10.3 
Protocol Deviations ............................................................................................................................ 17 
11 
REFERENCES .............................................................................................................................................. 18 
 
 
 

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STATEMENT OF COMPLIANCE 
 
The trial will be carried out in accordance with International Conference on Harmonization Good Clinical 
Practice (ICH GCP) and the following:  
 
• 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR 
Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812)  
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the Institutional Review Board (IRB) for review and approval.  Approval of both the 
protocol and the consent form must be obtained before any participant is enrolled.  Any amendment to 
the protocol will require review and approval by the IRB before the changes are implemented to the 
study.  In addition, all changes to the consent form will be IRB-approved; 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. 
 
 
 

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1 
LIST OF ABBREVIATIONS 
 
 
List in alphabetical order 
ADHD 
Attention-Deficit Hyperactivity Disorder 
AE 
Adverse Event 
API 
Attention Performance Index 
CFR 
Code of Federal Regulations 
CPT 
Continuous Performance Test 
CRF 
Case Report Form 
eCRF 
Electronic Case Report Form 
EEG 
Electroencephalography 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act of 2007 
GCP 
Good Clinical Practice 
GMP 
Good Manufacturing Practices 
HIPAA 
Health Insurance Portability and Accountability Act  
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization  
ICMJE 
International Committee of Medical Journal Editors 
IDE 
Investigational Device Exemption 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
MedDRA 
Medical Dictionary for Regulatory Activities 
NCT 
National Clinical Trial 
NT 
Neurotypical 
PI 
Principle Investigator 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SOA 
Schedule of Activities 
TOVA 
Test of Variables of Attention 
 
 
 

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1 
 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS  
 
 
Title: 
A study to assess Midline Frontal Theta (MFT) power as measured by 
stimulus-locked electroencephalography (EEG) before and after AKL-T01 
treatment for improving attention in pediatric participants ages 8-12 years 
old with Attention Deficit Hyperactivity Disorder (ADHD) 
 
Hypothesis: 
ADHD children receiving 4 weeks of AKL-T01 treatment will show 
enhancement in MFT activity as measure by stimulus-locked EEG. 
 
Objectives: 
 
Primary Objective: 
• 
Demonstrate enhancement of MFT power measured by stimulus-
locked EEG (Perceptual Discrimination Task (PDT)=Stimulus) in children 
with ADHD following 4 weeks of at-home AKL-T01 treatment. 
Secondary Objective: 
• 
Demonstrate normalized MFT power in children with ADHD following 
4 weeks of at-home AKL-T01 treatment. 
Exploratory Objectives: 
• 
Demonstrate improvement in sustained attention by direct 
assessment in children with ADHD following 4 weeks of at-home AKL-
T01 treatment. 
• 
Demonstrate improvement in ADHD symptoms by parent report in 
children with ADHD following 4 weeks of at-home AKL-T01 treatment. 
 
Endpoints: 
Primary Endpoint: 
• 
PDT-locked EEG relative to pre-training 
Secondary Endpoint: 
• 
PDT-locked EEG relative to a normative control cohort 
Exploratory Endpoints: 
• 
Project EVO Assessment 
• 
Test of Variables of Attention (TOVA) 
• 
Vanderbilt Assessment 
 
Study Population: 
30 children ages 8 to 12 with ADHD from the United States 
 
Description of Study 
Intervention: 
 
AKL-T01 is a digital therapeutic software for the treatment of attention 
and inhibitory control deficits in patients with ADHD. AKL-T01 is an 
investigational medical device known as Software as a Medical Device 
(SaMD). 
  
Study Duration: 
From beginning of enrollment to last subject last visit, 12 months 
  
Participant Duration: 
29 Days 
 
 

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1.2 
SCHEMA 
 
 
 
 

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1.3 
SCHEDULE OF ACTIVITIES (SOA) 
 
Procedures 
Screening* 
Day -7 to -3 
(Participants washing 
out stimulants only) 
Enrollment / 
Baseline* 
Day 0 
Treatment 
Days 1 to 27 
Follow Up 
Day 28 +3 
days 
Parent Informed consent 
 
X 
 
 
Child Assent 
 
X 
 
 
Mini-International Neuropsychiatric 
Interview for Children and 
Adolescents (MINI-KID) 
 
X 
 
 
Demographics 
X 
 
 
 
Medical history 
X 
 
 
 
Wechsler Intelligence Scale for 
Children V (WISC V) 
 
X 
 
 
Ishihara Colorblindness Test 
 
X 
 
 
Vanderbilt ADHD Diagnostic Parent 
Rating Scale (Initial and Follow-Up) 
 
X 
 
X 
Social Communication 
Questionnaire 
 
X 
 
 
Short Sensory Profile 
 
X 
 
 
Social Competence Scale 
 
X 
 
X 
Video Game Play Questionnaire 
 
X 
 
 
Behavior Assessment for Children, 
Second Edition (BASC-2) 
 
X 
 
 
Beery Visual Motor Integration 
(VMI) 
 
X 
 
 
Adaptive Cognitive Evaluation (ACE)† 
 
X 
 
X 
Neuroracer†-locked EEG 
 
X 
 
X 
Resting State EEG 
 
X 
 
X 
AKL-M01 (AKL-T01 Monitor) † 
 
X 
 
X 
Test of Variables pf Attention 
(TOVA)† 
 
X 
 
X 
Basic Response Time (BRT) 
 
X 
 
X 
Administer AKL-T01 
 
X 
 
 
AKL-T01 Compliance Monitoring 
 
 
X 
 
Adverse Event (AE) Assessment 
 
 
 
X 
Complete Case Report Forms (CRFs) 
X 
X 
X 
X 
 
* Screening and Baseline visits may be a combined visit for participants not washing out stimulant medication.  
† Interventions are computerized 
 
2 
 
INTRODUCTION 
 

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2.1 
BACKGROUND  
 
Akili Interactive’s videogame-like digital treatment, AKL-T01™ (EVO™-Multi), is based on the work of 
UCSF Professor Adam Gazzaley, MD, who has identified a way to measure and improve the ability to 
process interference events (essentially, interruptions and distractions). Interference susceptibility is 
recognized as a limiting factor across global executive function (including attention and memory) 
and is known to be fragile in multiple diseases. Dr. Gazzaley’s work also demonstrated that changes 
in EEG signals occurred at neurological loci associated with cognitive control. The basic scientific 
mechanisms underlying AKL-T01 have been tested in controlled (N=203) studies of healthy 
participants across a wide age range (8 to 70 years of age) to validate the ability to detect 
differences between age groups and to enhance interference processing in older adults.  AKL-T01 
was tested in a, follow-on, controlled (N=80) study of ADHD children and age-matched neurotypical 
controls to validate its ability to detect differences between the groups and to provide insight into 
AKL-T01 as a therapeutic product. Findings provide preliminary support that this digital treatment 
may improve attention, working memory, and inhibition in children with ADHD. The pivotal study 
STARS-ADHD; a multi-center, randomized, double-blind, active-controlled study of AKL-T01 in 348 
pediatric subjects ages 8-12 with ADHD demonstrated a statistically significant improvement 
(p=006) between AKL-T01 and an active control on the primary endpoint (TOVA API change from 
Baseline to Post-Treatment) (STARS-ADHD, in progress). 
 
Most relevant to this protocol is a published feasibility study of pediatric Sensory Processing 
Dysfunction (SPD at the University of California, San Francisco (UCSF), which requested that 57 
children ages 8 to 12 (24 Neurotypical, 20 SPD with inattention, and 13 SPD without inattention) to 
engage with AKL-T01 treatment at home for 30 minutes per day, 5 days per week for 4 weeks. 
Participants were assessed using EEG, TOVA and the Vanderbilt Inattention scale (parent-reported) 
at Baseline/Day 0 and at Exit/Day 28. All children showed statistically significant improvement in 
attention as measured by TOVA. Children with SPD and with inattention also showed statistically 
significant enhancement of Mid-Frontal Cortex Theta power as measured by EEG while neurotypical 
and SPD children without inattention did not. 
 
2.2 
STUDY RATIONALE  
 
Previous work has been done to establish the effect of AKL-T01 on MFT activity in children with SPD and 
inattention according to the Vanderbilt ADHD Diagnostic Parent Rating Scale, however no work has been 
done to study the effect of MFT activity in children with a confirmed diagnosis of ADHD.  
 
2.3 
RISK/BENEFIT ASSESSMENT   
 
2.3.1 KNOWN POTENTIAL RISKS  
 
The risks to the participants in this study are very small. The study involves completing some 
computerized tests, game-based digital therapies, and answering some questions. It is possible that the 
participant could become frustrated or fatigued by some of the tasks.  
 
The participant may also experience dizziness, headaches, nausea, decreased frustration tolerance, or 
emotional reaction as a result of playing the study device. If the participant becomes frustrated or 

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fatigued, they may stop at any time. There are no other risks to taking part in this study of which we are 
aware.  
 
2.3.2 KNOWN POTENTIAL BENEFITS  
 
Based on preliminary data obtained in several studies, including a feasibility study of AKL-T01 in 
pediatric SPD subjects, the potential benefits of the AKL-T01 game-based treatment for this population 
may include improvements in midline frontal theta activity and/or parental report of inattention. Given 
the central role of attention in the pathophysiology of ADHD, this benefit is substantial.  
 
2.3.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS  
 
To date, there have been no serious adverse events reported across several studies with the device. The 
risk/benefit ratio for use is favorable.  
 
3 
OBJECTIVES AND ENDPOINTS 
 
OBJECTIVES 
ENDPOINTS 
Primary 
Demonstrate enhancement of MFT power 
measured by stimulus-locked EEG (Perceptual 
Discrimination Task (PDT)=Stimulus) in children 
with ADHD following 4 weeks of at-home AKL-
T01 treatment. 
Change in midline frontal theta power as 
measured by PDT-locked EEG. 
 
Secondary 
Demonstrate normalized MFT power in children 
with ADHD following 4 weeks of at-home AKL-
T01 treatment. 
MFT power of ADHD cohort at Day 28 compared 
to that of neurotypical cohort at Day 0 (historical 
controls). 
Exploratory  
Demonstrate improvement in attention in 
children with ADHD following 4 weeks of at-home 
AKL-T01 treatment. 
• 
Reaction time and reaction time variability as 
measured by TOVA.  
• 
Reaction time and reaction time variability as 
measured by perceptual discrimination task.  
• 
Reaction time and reaction time variability as 
measured by ALK-M01 Assessment. 
 
 
4 
STUDY DESIGN  
 
4.1 
OVERALL DESIGN 
This study is a single arm, open-label, pilot study to assess midline frontal theta (MFT) power as 
measured by stimulus-locked electroencephalogram (EEG) before and after treatment with AKL-T01 for 
improving attention in pediatric participants ages 8-12 years old with attention deficit hyperactivity 
disorder (ADHD).  

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All participants enrolled in this study will not be taking ADHD medications, including stimulants, for the 
duration of the study. Participants who are taking ADHD medications prior to Day 0 must have been 
stable off of medications for at least 30 days per parent report, or washout of medications at a 
Screening visit 3 – 7 days prior to Day 0. 
At Baseline / Day 0, all eligible participants will complete both resting-state and PDT-locked EEG, as well 
as the TOVA, Vanderbilt, and AKL-M01 assessments.  
All participants will then play AKL-T01 for approximately 25 minutes per day, 5 days per week, for 4 
weeks at home.  
At Follow-up / Day 28, participants will repeat both resting-state and PDT-locked EEG, as well as the 
TOVA, Vanderbilt, and AKL-M01 assessments. 
All study visits for each participant should be completed during the same time of day (either AM or PM), 
to maintain consistent data collection and comparison of rater assessment results.  
 
4.2 
JUSTIFICATION FOR DOSE 
 
The therapeutic play regimen for the current study (typically 25 minutes per day; 5 days per week; 4 
weeks) was established based on previous work with AKL-T01 digital treatment. Specifically, a recent 
pivotal trial of AKL-T01 demonstrated that this regimen resulted in significant improvements in TOVA 
API scores in a sample of children with attention and inhibitory control deficits (STARS-ADHD). 
 
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. Age 8 to 12 at the time of parental informed consent  
2. Male or female  
3. Confirmed ADHD diagnosis at screening/baseline visit based on DSM-V criteria and 
established via the MINI-KID administered by a trained clinician either in person or via 
teleconference 
4. WISC V FSIQ ≥ 70  
5. Vanderbilt ADHD Diagnostic Parent Rating Scale: Must score a 2 or 3 on at least 6 items 1-9 
AND must score a 4 on at least 2, or 5 on at least 1, of items 48-54 (performance questions). 
6. Consistently off stimulant medication for ≥ 1 week. OR currently on stimulant medication 
and agree to stop taking the medication for a 1 week prior to the baseline visit and off 
through duration of training and post-training assessment (note: participants will only be 
allowed to washout of stimulant medication if in the opinion of the investigator they are 
currently inadequately managed on their medication and it is appropriate to stop taking 
their medication for the duration of the trial) 
7. Consistently off Psychotropic drug for ≥ 1 month 
8. Consistently off non-stimulant medication for ADHD (e.g. atomoxetine, clonidine, 
guanfacine) for ≥ 1 month 

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9. Able to follow written and verbal instructions (English) as assessed by the PI and/or study 
coordinator 
10. Functioning at an age-appropriate level intellectually 
11. Able to comply with all testing and requirements 
 
5.2 
EXCLUSION CRITERIA 
 
An individual who meets any of the following criteria will be excluded from participation in this study: 
1. Current controlled (requiring a restricted medication) or uncontrolled, comorbid 
psychiatric diagnosis, based on the Neurodevelopment Intake Form, BASC, and subsequent 
clinical interviewing, with significant symptoms including but not limited to post-traumatic 
stress disorder, psychosis, bipolar illness, severe obsessive compulsive disorder, severe 
depressive or anxiety disorder, conduct disorder, or other symptomatic manifestations 
that in the opinion of the Investigator may confound study data/assessments. (Participants 
with clinical history of learning disorders will be allowed to participate as long as the 
disorder does not impact their ability to participate based on PI judgement). 
2. Autism Spectrum Disorder concern as indicated from the Social Communication 
Questionnaire ≥ 15. 
3. Current treatment with stimulant treatment for ADHD and unwilling or inappropriate (per 
investigator opinion) to washout.  
4. Initiation or completion of behavioral therapy within the last 4 weeks.  The participant 
should inform the Investigator if they intend to change their behavioral therapy during the 
4 weeks of the study. Participants who have been in behavior therapy consistently for 
more than 4 weeks may participate if their routine is unchanged throughout the study.  
5. Participant is currently considered at risk for attempting suicide by the Investigator, has 
previously made a suicide attempt, or has a prior history of, or is currently demonstrating 
active suicidal ideation or self-injurious behavior, as measured by MINI-KID Suicidality 
Module C. 
6. Motor condition (e.g. physical deformity of the hands/arms) that prevents game playing as 
reported by the parent or observed by the Investigator. 
7. Recent history or suspicion (within the past 6 months) of substance abuse or dependence. 
8. History of seizures (excluding febrile seizures). 
9. Participation in a clinical trial within 90 days prior to screening. 
10. Color blindness as detected by Ishihara Color Blindness Test. 
11. Regular use of psychoactive drugs that in the opinion of the Investigator may confound 
study data/assessments. 
12. Any other medical condition that in the opinion of the Investigator may confound study 
data/assessments. 
13. Previously received AKL-T01 (Project-EVO™) treatment in a previous clinical trial. 
 
6 
STUDY INTERVENTION 
 
6.1 
STUDY INTERVENTION 
 
6.1.1 STUDY INTERVENTION DESCRIPTION 
 

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AKL-T01 digital treatment is a state-of-the-art mobile video game-like platform, which deploys modern 
videogame graphics, engaging reward loops, and real-time adaptive mechanics to dynamically 
personalize difficulty based on the user’s ability. AKL-T01 multitasking treatment employs perceptual 
discrimination attention/memory task as well as a continuous motor “driving” task. Performance on 
these tasks are assessed in isolation and when performed together to calculate a performance index for 
each individual user. A personalized multitask treatment regimen is automatically configured and 
delivered to the user and is optimized adaptively to increase multitask performance. As players proceed 
through the treatment periodic recalibration occurs to maintain an optimal difficulty level. 
6.1.2 STUDY INTERVENTION COMPLIANCE 
 
AKL-T01 automatically captures gameplay compliance and uploads these data directly to a central server 
when connected to WiFi. The server will automatically push daily compliance emails to the research 
coordinator. Based on these emails study staff can then reach out to parents and caregivers of 
participants to trouble shoot technical problems and/or encourage more play.  
 
Additionally, AKL-T01 contains built-in features that remind the participant to play each day.  
 
6.2 
CONCOMITANT MEDICATION AND TREATMENT 
 
With the exception of common over the counter (OTC) (e.g. ibuprofen, acetaminophen, non-sedating 
antihistamines to treat seasonal allergies) and prescription medications (e.g. antibiotics) for minor 
transient ailments, regular use of concomitant medications are not permitted during the study.  
 
Concomitant medications and treatment are as follow: 
1. Psychotropic medication 
2. Stimulant medication 
3. Non-stimulant medication for treatment of ADHD (e.g. atomoxetine, clonidine, guanfacine) 
 
Transient use of some non-sedating antihistamines is allowed.   
 
Study Investigators can approve short-term use of other medications that are not anticipated to confound 
study assessments. 
 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
 
7.1 
DISCONTINUATION OF STUDY INTERVENTION 
 
AKL-T01 study intervention may be discontinued by the participant or investigator at any time during 
the study.  
7.1.1 PARTICIPANT DISCONTINUATION OR WITHDRAWAL  
 

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Participants are free to withdraw from participation in the study at any time upon request without 
prejudice. 
 
An investigator may discontinue or withdraw a participant from the study for the following reasons: 
 
• 
Disease progression which requires discontinuation of the study intervention 
• 
If the participant meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation 
• 
Participant unable to receive AKL-T01 for 5 days/weeks as prescribed per protocol  
• 
If any clinical adverse event (AE) or other medical condition or situation occurs such that 
continued participation in the study would not be in the best interest of the participant 
 
The investigator or designee will notify the sponsor or their designee immediately when a subject has 
been discontinued or withdrawn from study treatment because of an adverse experience. Any adverse 
experiences that are present at the time of discontinuation/withdrawal should be reported and followed 
up in accordance with the safety requirements outlined in Section 8.3 (Adverse Events). 
 
7.1.2 LOST TO FOLLOW-UP 
 
A participant will be considered lost to follow-up if he or she fails to return for Day 28 Exit visit and is 
unable to be contacted by the study site staff.  
 
The following actions must be taken if a participant fails to return to the clinic for a required study visit: 
• 
The site will attempt to contact the participant and reschedule the missed Follow-up / Day 
28 visit.  
• 
Before a participant is deemed lost to follow-up, the investigator or designee will make 
every effort to regain contact with the participant. 
• 
Should the participant 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. 
 
8 
STUDY ASSESSMENTS AND PROCEDURES 
 
8.1 
ELIGIBILITY AND EFFICACY ASSESSMENTS  
 
The following assessments will be administered to each eligible participant  
 
Assessment 
Purpose 
Time to Administer 
Eligibility 
MINI-KID 
 
Confirm diagnosis of ADHD and 
identify any excluding comorbid 
diagnoses  
20 minutes 
WISC V 
Determine IQ 
60 minutes 
Ishihara Colorblindness Test 
Determine colorblindness 
5 minutes 
Efficacy 

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Assessment 
Purpose 
Time to Administer 
Vanderbilt ADHD Diagnostic Parent 
Rating Scale 
Assess severity of ADHD symptoms 
and effect on behavior. 
20 minutes 
Resting State EEG 
Assess MFT activity in a resting state 
6 min 
PDT-locked EEG 
Assess MFT activity during a 
Perceptual Discrimination Task 
1 hour 
Test of Variables of Attention 
(TOVA) 
Assess objective attention 
22 minutes 
AKL-M01 (EVO Monitor) 
Assess MFT activity during a AKL-M01 
session 
20 minutes 
 
 
8.2 
SAFETY AND OTHER ASSESSMENTS 
 
Safety assessments will include the evaluation of adverse device effects (ADEs). 
   
8.3 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
 
8.3.1 DEFINITION OF ADVERSE DEVICE EFFECTS (ADE) 
 
An ADE is an adverse event related to the use of an investigational medical device. This includes any 
adverse event resulting from insufficiencies or inadequacies in the instructions for use, the deployment, 
the implantation, the installation, the operation, or any malfunction of the investigational medical 
device. This also includes any event that is a result of a user error or intentional misuse. 
 
8.3.2 DEFINITION OF UNANTICIPATED ADVERSE DEVICE EFFECTS (UADE)  
 
Per 21 CFR 812.3, an Unanticipated Adverse Device Effect is 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 
participants. 
 
Unanticipated Adverse Device Effects will include events meeting BOTH A and B as stated below: 
A. Events meeting ALL of the following criteria: 
1) Not included in the list of Anticipated Events (refer to protocol Section 8.3.3) 
2) Possibly, probably, or definitely related to the investigational device (per the sponsor)  
B. Serious (meets any of the following criteria): 
1) Is life-threatening illness or injury 
2) Results in permanent impairment of a body function or a body structure 
3) Necessitates medical or surgical intervention to prevent permanent* impairment of a 
body function or a body structure. (*Permanent* is defined as irreversible impairment 
or damage to a body structure or function, excluding trivial impairment or damage) 
4) Leads to fetal distress, fetal death or a congenital abnormality or birth defect 
5) Leads to death. 

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8.3.3 PREVIOUSLY KNOWN ADVERSE DEVICE EFFECTS 
 
The expectedness of an ADE shall be determined according to the Instructions for Use and the expected 
ADEs listed below. Any ADE that is not identified in nature, severity, or specificity in the current 
investigational product reference documents is considered unanticipated.  
 
Adverse Device Effects expected for this device are as follows: 
• 
Dizziness 
• 
Nausea 
• 
Headache  
• 
Decreased frustration tolerance 
• 
Emotional reaction 
 
8.3.4 CLASSIFICATION OF AN ADVERSE EVENT 
8.3.4.1 SEVERITY OF EVENT 
 
The following guidelines will be used to describe severity of an ADE:  
 
• 
Mild – Events require minimal or no treatment and do not interfere with the participant’s 
daily activities.  
• 
Moderate – Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning. 
• 
Severe – Events interrupt a participant’s usual daily activity and may require systemic drug 
therapy or other treatment. Severe events are usually potentially life-threatening or 
incapacitating.  Of note, the term “severe” does not necessarily equate to “serious”. 
 
8.3.4.2 RELATIONSHIP TO STUDY TREATMENT 
 
All ADEs must have their relationship to study treatment assessed by the clinician who examines and 
evaluates the participant based on temporal relationship and his/her clinical judgment. In a clinical trial, 
the investigational device must always be suspect. The degree of certainty of causal relationship of an 
adverse device effect of either study treatment will be rated as follows: 
▪ 
Possible: An event that might be due to the use of the study device. An alternative explanation, 
e.g., concomitant drug(s), concomitant disease(s), is inconclusive. The relationship in time is 
reasonable; therefore, the causal relationship cannot be excluded. 
▪ 
Probable: An event that might be due to the use of the study device. An alternative explanation 
is less likely - e.g., concomitant drug(s), concomitant disease(s). The relationship in time is 
suggestive. 
▪ 
Definitely: An event that is due to the use of the study device. The event cannot be reasonably 
explained by an alternative explanation - e.g., concomitant drug(s), concomitant disease(s). 
 
8.3.4.3 EXPECTEDNESS  
 

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Akili Interactive Labs, Inc will be responsible for determining whether an adverse event (AE) is expected 
or unexpected.  An 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 study treatment. 
8.3.5 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
The occurrence of an ADE may come to the attention of study personnel during study visits and 
interviews of a study participant presenting for medical care, or upon review by a study monitor. 
Information to be collected includes event description, time of onset, clinician’s assessment of severity, 
relationship to study product (assessed only by those with the training and authority to make a 
diagnosis), and time of resolution/stabilization of the event. All ADEs occurring while on study will be 
documented appropriately regardless of relationship. All ADEs will be followed to adequate resolution. 
Any medical condition that is present at the time that the participant is screened will be considered as 
baseline and not reported as an ADE. However, if the study participant’s condition deteriorates at any 
time during the study, it will be recorded as an ADE.  
Changes in the severity of an ADE will be documented to allow an assessment of the duration of the 
event at each level of severity to be performed. ADEs characterized as intermittent require 
documentation of onset and duration of each episode. 
The Site Principal Investigator will record all reportable events with start dates occurring from the time 
of enrollment through the final study visit.  At each study visit, the investigator will inquire about the 
occurrence of ADEs since the last visit. Events will be followed for outcome information until resolution 
or stabilization. 
8.3.6 ADVERSE EVENT REPORTING  
 
It is understood that complete information about an event may not be known at the time the initial 
report is submitted.  The investigator must assess the relationship of the event to the investigational 
device (including rationale for assessment) and should make every attempt to obtain as much 
information as possible concerning the event.  Additional information pertaining to an event should be 
reported in the case report form as it becomes available.  
 
The investigator must report all adverse device effects (anticipated or unanticipated) occurring from the 
time of enrollment through the final study visit within 24 hours of knowledge of the event.  
 
The investigator must report when important follow-up information (final diagnosis, outcome, results of 
specific investigations, etc.) becomes available after submission of the initial ADE form and information. 
Follow-up information should be submitted according to the same process used for reporting the initial 
event as described above (i.e., within 24 hours of knowledge, via <specify method>). All adverse device 
effects will be followed through resolution.   
 
8.4 
UNANTICIPATED PROBLEMS 
 
8.4.1 DEFINITION OF UNANTICIPATED PROBLEMS (UP) 
 

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The Office for Human Research Protections (OHRP) considers unanticipated problems involving risks to 
participants or others to 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 Institutional Review Board 
(IRB)-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. 
 
In addition, UPs include unanticipated adverse device effect, 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 (21 CFR 812.3(s)). 
 
• 
Examples of potential UPs include but are not limited to: 
1. Unanticipated misuse of device hardware 
2. Unanticipated misuse of device software 
3. Unanticipated hardware issues 
4. Unanticipated software issues 
 
8.4.2 UNANTICIPATED PROBLEM REPORTING  
 
The investigator will report unanticipated problems (UPs) to the reviewing Institutional Review Board 
(IRB) and to the Data Coordinating Center (DCC)/lead principal investigator (PI). The UP report will 
include the following information: 
 
• 
Protocol identifying information: protocol title and number, PI’s name, and the IRB project 
number; 
• 
A detailed description of the event, incident, experience, or outcome;  
• 
An explanation of the basis for determining that the event, incident, experience, or outcome 
represents an UP;  
• 
A description of any changes to the protocol or other corrective actions that have been 
taken or are proposed in response to the UP. 
 
An investigator shall submit to the sponsor and to the reviewing Institutional Review Board (IRB) a 
report of any unanticipated adverse device effect occurring during an investigation as soon as possible, 
but in no event later than 10 working days after the investigator first learns of the effect (21 CFR 
812.150(a)(1)). A sponsor who conducts an evaluation of an unanticipated adverse device effect under 
812.46(b) shall report the results of such evaluation to the Food and Drug Administration (FDA) and to 
all reviewing IRBs and participating investigators within 10 working days after the sponsor first receives 

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notice of the effect. Thereafter the sponsor shall submit such additional reports concerning the effect as 
FDA requests (21 CFR 812.150(b)(1)).    
 
9 
STATISTICAL CONSIDERATIONS  
 
9.1 
STATISTICAL HYPOTHESES 
 
OBJECTIVE 
HYPOTHESIS 
Primary 
 
Children with ADHD, following 4 weeks of digital treatment 
with AKL-T01, will demonstrate enhancement of MFT power as 
measured by stimulus-locked EEG.  
 
Secondary 
Children with ADHD, following 4 weeks of digital treatment 
with AKL-T01, will demonstrate normalized MFT power as 
compared with a neurotypical population. 
 
 
9.2 
POPULATIONS FOR ANALYSES 
 
There will be two populations for analysis in this study. 
 
The AKL-T01 Intervention Population will complete 28 days of AKL-T01 digital treatment. This population 
will enroll pediatric ADHD participants according to the inclusion criteria outlined in section 5.1 of this 
protocol. Only participants completing at least 50% of the prescribed treatment (i.e. 50 sessions) will be 
included in the analysis.  
 
The neurotypical control group will also be analyzed as historical controls. This population was enrolled 
in A pilot study to determine the feasibility of enhancing cognitive abilities in children with sensory 
processing dysfunction (Anguera, 2017).   
 
9.3 
STATISTICAL ANALYSES 
 
All statistical analyses will be conducted using SPSS 22.0 (SPSS Inc.). Group effects for both behavioral 
and neural measures will be assessed with separate ANOVAs and ANCOVAs with planned follow-up 
contrasts (Fisher’s LSD). The ANCOVA approach is considered to be a more suitable approach when post-
test performance that is not conditional / predictable based on pre-test performance is the primary 
outcome of interest following treatment, as opposed to characterizing gains achieved from pre-training 
performance (for example, group X session interaction(s). However, both are appropriate statistical 
approaches that have been used to assess cognitive training outcomes. Thus, our approach will be to 
present the p-values for each approach. Planned follow-up contrasts will be used to directly assess 
changes within each group. To minimize influential data points, we will remove values +/- 2 standard 
deviations for all group analyses. For correlations tested, we will use a more stringent outlier removal 
procedure (Cook’s D> 1) given the smaller cohort size and possible inflated change scores. 
 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 

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10.1 CONFIDENTIALITY AND PRIVACY  
 
Participant confidentiality and privacy is strictly held in trust by the participating investigators, their 
staff, and the sponsor(s) and their interventions. The study protocol, documentation, data, and all other 
information generated will be held in strict confidence. No information concerning the study or the data 
will be released to any unauthorized third party without prior written approval of the sponsor.  
 
10.2 DATA HANDLING AND RECORD KEEPING  
 
10.2.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the 
principal 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.  Data recorded in the electronic case report form (eCRF) derived from source documents should 
be consistent with the data recorded on the source documents.  
 
10.2.2 STUDY RECORDS RETENTION  
 
Study documents should be retained for a minimum of 2 years after the last approval of a marketing 
application in an International Conference on Harmonization (ICH) region and until there are no pending 
or contemplated marketing applications in an ICH region or until at least 2 years have elapsed since the 
formal discontinuation of clinical development of the study intervention. These documents should be 
retained for a longer period, however, if required by local regulations. No records will be destroyed 
without the written consent of the sponsor. It is the responsibility of the sponsor to inform the 
investigator when these documents no longer need to be retained. 
 
10.3 PROTOCOL DEVIATIONS  
 
A protocol deviation is any noncompliance with the clinical trial protocol, ICH GCP, or Manual of 
Procedures (MOP) requirements. The noncompliance may be either on the part of the participant, the 
investigator, or the study site staff. As a result of deviations, corrective actions are to be developed by 
the site and implemented promptly.  
 
 

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11 REFERENCES  
 
Anguera, J. A., Boccanfuso, J., Rintoul, J. L., Al-Hashimi, O., Faraji, F., Janowich, J., ... & Gazzaley, A. 
(2013). Video game training enhances cognitive control in older adults. Nature, 501(7465), 97. 
 
Anguera, J. A., Gunning, F. M., & Areán, P. A. (2016). Improving late life depression and cognitive control 
through the use of therapeutic video game technology: A proof‐of‐concept randomized trial. Depression 
and anxiety, 34(6), 508-517. 
 
Anguera, J. A., Brandes-Aitken, A. N., Antovich, A. D., Rolle, C. E., Desai, S. S., & Marco, E. J. (2017). A 
pilot study to determine the feasibility of enhancing cognitive abilities in children with sensory processing 
dysfunction. PloS one, 12(4), e0172616.