A Randomized, Controlled, Parallel-group, Intervention Study to Assess At-home, Game-based Digital Therapy for Treating Pediatric Participants Ages 8 to 12 Years Old With Attention Deficit Hyperactivity Disorder (ADHD)
Phase: NA
Conditions: Attention Deficit Disorder With Hyperactivity
Sponsor: Akili Interactive Labs, Inc.

Akili Interactive Labs, lnc . 
"EVO" Revision 4.3C, ADHD Therapeutic Game 
aKILI 
Akili-001R 
Version 1.02 
1.02 
Akili-OOIR 
A randomized, controlled parallel-group, intervention study 
to assess at-home, game-based digital therapy for treating 
pediatric participants ages 8 to 12 years old with Attention 
Deficit Hyperactivity Disorder (ADHD) 
Date: August 4, 16 
Version: 1.02 
Principal Investigator : 
Scott H. Kollins, Ph.D. 
Confident ial 
Medical Monitor: 
Andrew Krystal, M.D. 
Akili Interactive Labs, Inc. 
1.02 /4-Aug-16 

Aklli Interactive Labs, Inc. 
"EVO" Revision 4.3C, ADHD Therapeutic Game 
PROTOCOL 
APPROVAL 
PAGE 
1.02 
Akili-001 R 
Study Title: A randomized, controlled parallel-group, intervention study to assess at-
home game-based digital therapy for treating pediatric participants ages 8 to 12 years 
old with Attention Deficit Hyperactivity Disorder (ADHD). 
Version: 
Date of Issue: 
Study Sponsor: 
1.02 
August 4, 16 
Akili Interactive Labs, Inc. 
125 Broad St., 4th Floor 
Boston, MA 02110 
We, the undersigned, have read and approve this protocol and agree on its content. 
Sponsor Representative 
~fa/1, 
Date 
Principe~ 
Date 
Confidential 
1.02 /4-Aug-I 6 
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Akili Interactive Labs, Inc. 
"EVO" Revision 4.3C, ADHD Therapeut ic Game 
1.02 
Akili-00IR 
PROTOCOL VERSION AND AMENDMENT TRACKING 
Version 
Number/Amendment 
Approval Date 
1.00 
11/17/15 
1.01/ Amendment 1 
04/06/16 
1.02/Amendment 2 
07/25/16 
Summary of Changes 
Amendment 2: 
1) Updated information regarding participant's ability to access 3rd party applications, 
download additional applications, and store personal information. 
2) Added requirement for sites to hold and document a discussion with each 
participant to describe intended and unintended use of the device, as well as 
study restrictions and requirements. 
3) Added requirement for sites to return the device to Akili for complete erasing of all the 
data entered prior to re-circulating the device. 
4) Updated description of the secondary and descriptive endpoints to be consistent with 
the current SAP 
5) Added detail on administering the IRS 
Amendment 1 : 
1) Updated Akili business address to reflect current location 
2) Attention Performance Index (API) is an output of TOVA version 8. Specified 
"TOVA 8" where TOVA is mentioned in conjunction with API. Also added clarity 
that API is a "composite measure" 
3) Added analysis of TOVA non-composite measures to the secondary endpoints 
4) Added exclusion criteria that potential subjects could not have previously 
participated in any assessment of Akili's videogame-like digital therapy 
5) Clarified the study design that the Investigators and Outcome Assessors are 
blinded to the treatment assignment. 
6) Added analysis of responders and descriptive analysis as exploratory endpoints 
7) Timing of interim analysis update to reflect N = 75/75 
8) Clarified that maximum enrolment , following interim analysis, is 1000 subjects 
9) Added a baseline visit expectation survey for the parents to complete 
10)To better preserve the blinding, removed the "A" I "B" labeling of the iPads 
(previously corresponding to treatment assignment) and included an anonymous 
serial number. A separate blinded treatment assignment list will be generated 
11)Clarified instructions for connecting via remote Wi-Fi locations 
12) Updated the statistical analysis section to reference details that are described in 
a separate statistical analysis plan (SAP) and added a non-inferiority test to the 
primary objective 
13)Clarified subject replacement criteria to include subjects that don't complete the 
in-clinic exit assessments 
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Akili Interactive Labs, Inc. 
"EVO" Revision 4.3C, ADHD Therapeutic Game 
1.02 
Akili-00IR 
14)Require participants to be able to spell at least 2 words during EVO Words 
assessment 
15)Added requirement where same study staff administers the ADHD-RS, CGI, and 
IRS pre/post visits 
16)Capture any unblinding event in the CRF 
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Akili Interactive Labs, Inc. 
"EVO" Revision 4.3C, ADHD Therapeutic Game 
1.02 
Akili-00IR 
Name of Company 
Study Product 
Protocol Number 
Protocol Title 
Main Criteria for Inclusion 
Confidential 
PROTOCOL SYNOPSIS 
Akili Interactive Labs, Inc., 125 Broad Street, 4th 
Floor, Boston, MA 02110 
"EVO", 
Multi-tasking 
Game-Based 
Digital 
Therapy or "EVO" Words Game-Based Digital 
Therapy 
Akili-001 R 
A 
randomized , 
controlled 
parallel-group, 
intervention study to assess at-home, game-
based digital therapy for treating pediatric 
participants ages 8 to 12 years old with 
Attention Deficit Hyperactivity Disorder (ADHD) 
Inclusion 
• 
Age 8 years to 12 years, inclusive, at 
the time of parental informed consent 
• 
Male or female 
• 
Confirmed ADHD diagnosis, any 
presentation , at Screening based on 
DSM-V criteria and established via the 
MINI-KID administered by a trained 
clinician 
• 
Screening/Baseline (Visit 1 or 1 a) 
score on the clinician-rated ADHD-RS-
IV score~ 28 
• 
Screening/Baseline (Visit 1 or 1 a) 
score on the TOVA 8 API 
-1.8 
• 
Not undergoing pharmacological 
treatment with methylphenidate or 
amphetamine -based products at time 
of Screening ; or, if undergoing 
pharmacological treatment , must be 
willing and appropriate (i.e. not 
optimally treated in the investigator's 
judgment ) to wash out of current 
regimen. 
• 
Ability to follow written and verbal 
instructions (English), as assessed by 
the Pl and/or study coordinator 
• 
Estimated IQ score~ 80 as assessed 
by the Kaufmann Brief Intelligence 
Test, Second Edition (KBIT-11) 
1.02 /4-Aug-I 6 
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"EVO" Revision 4.3C, ADHD Therapeutic Game 
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• 
Ability to comply with all the testing and 
requirements . 
Exclusion 
• 
Current, controlled (requiring a 
restricted medication) or uncontrolled , 
comorbid psychiatric diagnosis, based 
on MINI-KID and subsequent clinical 
interviewing, with significant symptoms 
including but not limited to post-
traumatic stress disorder , psychosis, 
bipolar illness , pervasive 
developmental disorder, severe 
obsessive compulsive disorder , severe 
depressive or severe anxiety disorder, 
conduct disorder, or other symptomatic 
manifestations that in the opinion of the 
Investigator that may confound study 
data/assessments . Participants with 
clinical history of learning disorders will 
be allowed to participate, provided the 
disorder does not impact their ability to 
participate in the trial based on Pl 
judgment 
• 
Participants who are currently treated 
with a non-stimulant medication for 
ADHD (i.e., atomoxetine , clonidine , 
guanfacine) 
• 
Initiation within the last 4 weeks of 
behavioral therapy . Participants who 
have been in behavior therapy 
consistently for more than 4 weeks 
may participate provided their routine is 
unchanged during the course of the 
study. Participants planning on 
changing or initiating behavior therapy 
during the course of the study will be 
excluded . 
• 
Participant is currently considered a 
suicide risk in the opinion of 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 C-SSRS at 
screeninQ. 
1.02 /4-Aug- I 6 
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Akili Interactive Labs, Inc. 
"EVO" Revision 4.3C, ADHD Therapeutic Game 
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Akili-00IR 
Confidential 
• 
Motor condition (e.g., physical 
deformity of the hands/arms; 
prostheses) that prevents game playing 
as reported by the parent or observed 
by the investigator. 
• 
Recent history (within the past 6 
months) of suspected substance abuse 
or dependence . 
• 
History of seizures (exclusive of febrile 
seizures) , or significant motor or vocal 
tics , including but not limited to 
Tourette's Disorder . 
• 
Has participated in a clinical trial within 
90 days prior to screening. 
• 
Diagnosis of or parent-reported color 
blindness (Confirmed in-clinic via ICBT) 
• 
Uncorrected visual acuity (Confirmed 
in-clinic via ability of subject to play the 
game) 
• 
Regular use of psychoactive drugs 
(other than stimulant ) that in the 
opinion of the Investigator may 
confound study data/assessments. 
• 
Any other medical condition that in the 
opinion of the investigator may 
confound study data/assessments . 
• 
Has a sibling also enrolled/currently 
participating in the same study 
• 
Has previously participated in a study 
of Akili's videogame-l ike digital therapy 
Concomitant Medication and Treatment 
• 
With the exception of common over the 
counter (OTC) (e.g. ibuprofen, 
acetaminophen) and prescription 
medications (e.g. antibiotics ) for minor 
transient ailments , regular use of 
concomitant medications (i.e., sleep 
aids, etc.) are not permitted during the 
study. Transient use of some 
medications (i.e., non-sedating 
antihistamines to treat seasonal 
allergies) may be permitted on a case-
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Akili Interactive Labs, Inc. 
"EVO" Revision 4.3C, ADHD Therapeutic Game 
1.02 
Akili-00IR 
Study Objective 
Study Design 
Treatment Regimen 
Duration 
of 
Participation 
Number of Participants 
Number of Sites 
Primary Endpoint 
Confidential 
by-case basis with Pl and medical 
monitor review/approval. Families should 
advise the study staff if it becomes 
necessary to use other types of 
medication. Study investigators can 
approve short-term use of other 
medications that are not anticipated to 
confound study assessments. 
• 
Initiation of or significant changes in non-
pharmacological treatment for ADHD is 
not permitted during the course of the 
study. Participants actively engaged in 
non-pharmacological treatment at 
Screening, may be eligible if they meet 
all inclusion criteria and do not undergo 
changes to their treatment during the 
course of the study. 
To evaluate the effects of EVO Multitasking 
digital therapy versus EVO Words digital 
therapy on attentional functioning (measured by 
the 
TOVA) 
and 
symptoms 
in 
children 
diagnosed with ADHD 
Blinded (Investigator / Outcome Assessor), 
Randomized, Parallel-group 
25 minutes/day for 5 days/week of either EVO 
multitasking digital therapy or EVO Words 
digital therapy across the 4-week (28 Day) 
treatment period. 
Study 36 days 
A minimum of 300 to a maximum of 1,000 
participants will be enrolled to achieve a 
minimum of 300 to a maximum 900 completed 
participants (n=150 - 450 in each of 2 arms) 
evaluable 
6-9 
Change (from Study Day O to Study Day 28) on 
the Attention Performance Index (API), an 
overall composite score, from the Test of 
Variables of Attention (TOVA 8) 
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Akili Interactive Labs, Inc. 
"EVO" Revision 4.3C, ADHD Therapeutic Game 
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Secondary Endpoints 
Exploratory/Descriptive 
Endpoints 
Interim Analyses 
Confidential 
Change (from Study Day Oto Study Day 28) in: 
• ADHD Symptoms as reported on the 
AOHD-RS 
total 
score, 
ADHD-RS 
Inattentive 
Sub-scale, 
ADHD-RS 
hyperactivity sub-scale, BRIEF working 
memory 
percentile, 
BRIEF 
inhibit 
percentile, Impairment Rating Scale, and 
Clinical Global Impression Scale. 
• 
Objective Working Memory as measured 
by the CANTAB spatial working memory 
test 
• 
Objective Inhibition as measured by the 
TOVA commission error standard score 
in half-2. 
Analysis includes: 
• 
Responder 
analysis, 
percentage 
of 
responders to primary and secondary 
endpoints 
• 
Descriptive 
analysis 
of 
child/parent 
surveys, treatment regimen compliance, 
demographics, 
missing 
data, 
site 
poolability, and any resulting treatment 
related AEs 
• Analysis of secondary symptom and 
executive function endpoints adjusted for 
baseline parent expectations 
An interim analysis will be conducted at N =75 / 
75 (EVO Multitask / EVO Words) to confirm 
powering and to finalize sample size 
1.02 /4-Aug- I 6 
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Akili Interactive Labs, Inc. 
"EVO" Revision 4.3C, ADHD Therapeutic Game 
INVESTIGATOR STATEMENT 
1.02 
Akili-00IR 
I have read the protocol, including all appendices and I agree that it contains all 
necessary details for me and my staff to conduct this study as described. I will 
personally oversee the conduct of this study as outlined herein and will make a 
reasonable effort to complete the study within the time designated. 
I will provide all study personnel under my supervision with copies of the protocol 
and access to all information provided by Akili Interactive Labs, Inc. [Sponsor]. I 
will discuss this material with them to ensure that they are fully informed about 
the efficacy and safety parameters and the conduct of the study in general. I am 
aware that, before beginning this study, the institutional review board responsible 
for such matters must approve this protocol in the clinical facility where it will be 
conducted. I agree to make all reasonable efforts to adhere to the attached 
protocol. 
I agree to provide all participants with informed consent forms, as required by 
government and International Conference on Harmonization regulations. I further 
agree to report to the sponsor any adverse experiences in accordance with the 
terms of this protocol and U.S. Food and Drug Administration regulation 21 Code 
of Federal Regulations 812.2(b). 
Principal investigator Name (print) 
Signature 
Date 
Contents 
aKILI 
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Akili lnteractive Labs, Inc. 
1.02 
"EVO" Revision 4.3C, ADHD Therapeutic Game 
Akili-00 IR 
Akili-001 R ....................................................................................................................... 1 
Version 1.01 ..................................................................................................................... 1 
Protocol Approval Page .......................... ...................................... ................ ...................... . 2 
Protocol Version and Amendment Tracking ............. ........................................................ .. 3 
Protocol Synopsis ................................................ ................... .............................................. 5 
Investigator statement .................................................... ............................. ....................... 10 
1. Introduction .............................................................................................................. 16 
1.1 Background .................................................................................................. 16 
1.2 
Clinical Experience with Study Agent (s) .............................................. 16 
1.2.2 Rationale ................................................................................................... 19 
2. Objectives ................................................................................................................... 21 
2 .1 
Primary Objective .................................................................................... 21 
2.2 
Secondary Objectives ........................................................................... 21 
2.3 
Exploratory & Descriptive Objectives .................................................. 21 
3. Subject Selection ....................................................................................................... 22 
3.1 
Inclusion Criteria ................................................................................... 22 
3.2 
Exclusion Criteria .................................................................................... 22 
3.3 
Concomitant Medications and Treatments .... ...... .... ...... ..... ..... 23 
4. Study 
Design .... ...... .... ...... .... ...... ......... ..... ....... ..............
...... ..... ..... 25 
4.1. overview of Study ................................................................................................... 25 
4.2 
Treatment Arms .................................................................................... 26 
4.3 
Screening/Baseline Procedures ......................................................... .29 
4.4 
Washout Procedures & Screening/Baseline (Post Was hout) 
Procedures ............................................................................................... 32 
4.5 
Treatment Procedures - In-Home Game Play and Post-
Treatment Visit. ...................................................................................... 34 
4.6 
Procedures to minimize bias and blinding to treatment 
assignment .............................................................................................. 36 
4.6.1 
Procedures to minimize bias in parents and 
participants ................................................................................ 3 7 
4.6.2 
Procedures to blind/minimize bias in site staff and 
investigators ............................................................................ 3 7 
4.6.3 
Procedures in the event of possible or probable 
unblinding . ............................................................................... 38 
4.7 Randomization Procedures ...........................................
... ........ 38 
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Akili Interactive Labs, Inc. 
1.02 
"EVO" Revision 4.3C, ADHD Therapeutic Game 
Akili-00IR 
5 Study Device ............................................................................................................... 39 
5.1 Study Device Usage ..................................................................................... 
39 
5.2 Potential Benefits/Risks of Study Device ................................................. 
.41 
5.3 Procedures for Monitoring Compliance and Replacing Participants ... .42 
5.3 Discontinuation of Study Device ............................................................... 
.43 
6 Concomitant Medications ........................................................................................... 
44 
6.1 Allowed Medications ....................................................................... .44 
6.2 Prohibited Medications ...............................................
.................... .44 
7. 0 Adverse Device Effect Reporting and Follow-up ............................................... 
.45 
7.1 
Definitions .................................................................................................. 45 
Unanticipated Adverse Device Effects (UADEs) ........................................... 
.45 
7.2 
Assessment .............................................................................................. 46 
7.2.1Time Frame ................................................................................................ 46 
7.2.2 Causality Rating ..................................................................................... 46 
7.2.3 Severity of Adverse Device Effects ...............................................
........ .46 
7.3 Previously Noted Adverse Device Effects ............................................... 
.47 
7.4 
Reporting .................................................................................................. 47 
7.4.1 Adverse Device Effect. ............ .............................
......... ...... .46 
7.4.2 Regulatory Reporting of Unanticipated Adverse Device Effects ...... .48 
7.5 Institutional Review Boards ......................
....... ........ ......... ......... ....... 47 
8.0 Statistical Analysis e ................................................................................................ 48 
8.1 Primary Objective (P1) -Attention ............................................................ .49 
8.2 Secondary Objectives .................................................
................................. 
50 
8.2.1 Major Secondary Objective 1 (ST) ADHD Symptom ............ 50 
8.2.2 Minor Secondary Objective II (S2) Objective Working 
Memory ................................................................................... 
50 
8.2.3 Minor Secondary Objective Ill (s3) Objective Inhibition ......... 51 
8.3 Exploratory Objectives ................................................................................ 
51 
8.3.1 Exploratory Objective 1 (E1) Responders ................................ 51 
8.3.2 Exploratory Objective II (E2) Additional TOVA 
Responses ................................................................................ 51 
8.4 Safety Analysis ............................................................................................. 
52 
8.5 Descriptive Analyses ................................................................................... 52 
8.6 General Statistical Methods ........................................................................ 52 
8.6.1 Hypothesis Tests and Multiplicity Adjustments ....................... 52 
8.6.2 
Analysis Populations and Missing Data ............................... 53 
8.6.3 Interim Analysis .......... .. .... .... ..... .... .... .... ........ ... ...... .. 53 
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"EVO" Revision 4.3C, ADHD Therapeutic Game 
Akili-00 IR 
8.6.4 Power and Sample Size ............................................................... 53 
9. Data and Safety Monitoring ....................................
................................................... 55 
9.1 
Endpoint Determination .........................................................................
. 55 
9.2 
Safety Monitoring .................................................................................. 55 
9.3 
Data Management to Maintain Blinding ............................................. 55 
10 
Data Monitoring and Quality Control ................................................................ 
56 
10.1 Required Data ....................................
........................................................ 
56 
10.2 Subject and Clinical Data ........................................................................ 56 
11 
Study Responsibilites ....................................................................................... 57 
11.1 Study Data Reporting and Processing .............................................
....... 57 
11.2 Training ....................................................................................................... 57 
11.3 Monitoring the lnvestigational Sites ........................................................ 
57 
11.4 Study Documentation .............................................................................. 58 
11.5 Protocol Deviations ................................................................................. 58 
11.6 Study Supply Accountability ................................................................... 
59 
11. 7 Data Transmittal and Record Retention ................................................ 
59 
11.8 Study Closeout ......................................................................................... 60 
11.9 AudiUlnspections ...................................................
..................................... 60 
12 
References .......................
........ ... ...........................
..... ...... ..... 61 
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Akili Interactive Labs , Inc. 
"EVO" Revision 4.3C, ADHD Therapeutic Game 
Abbreviations 
ADHD 
Attention Deficit Hyperactivity Disorder 
DSM-V 
Diagnostic and Statistical Manual of Mental Health-Fifth Edition 
1.02 
Ak.ili-OOIR 
MINI-KID 
MINI International Neuropsych iatric Interview for Children and Adolesce nts 
ADHD-RS-
Attention Deficit Hyperactivity Disorder Rating Scale 
IV 
TOVA 
Test of Variables of Attention 
API 
Attent ion Performance Index 
KBIT 
Kaufman Brief Intelligence Test 
Pl 
Principal Investigator 
C-SSRS 
Columbia Suicide Severity Rating Scale 
ICBT 
Ishihara Color Blindness Test 
OTC 
Over the counter 
CANTAB 
Cambridge Neuropsychological Test Automated Battery 
BRIEF 
Behavior Rating Inventory of Executive Function 
CGl-1 
Clinical Global Impression-Improvement 
IRS 
Impairment Rating Scale 
ASD 
Autism Spectrum Disorder 
LD 
Learning Disability 
CANTAB 
Cambr idge Neuropsychological Test Automated Battery Spatial Working Memory 
SWM 
ICF 
Informed Consent Form 
DCRI 
Duke Clinical Research Institute 
SSRI 
Selective Serotonin Reuptake Inhibitor 
MAOI 
Monoamine Oxidase Inhibitor 
ADE 
Adverse Device Effect 
UADE 
Unanticipated Adverse Device Effect 
eCRF 
Electronic Case Report Form 
FDA 
Food and Drug Administration 
IRB 
Institutional Review Board 
CPT 
Continuous Performance Test 
ComSS 
Commission Error Standard Score 
ROC 
Receiver Operator Curve 
SAP 
Statistical Analysis Plan 
APP 
Applicat ion 
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Akili Interactive Labs, Inc. 
"EVO" Revision 4.3C, ADHD Therapeutic Game 
GCP 
Good Clinical Practice 
CMP 
Clinical Monitoring Plan 
HIPPA 
Health Insurance Portability and Accountability Act 
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Akili-00I R 
15 

Akili Interactive Labs, Inc. 
"EVO" Revision 4.3C , ADHD Therapeutic Game 
1. INTRODUCTION 
1.1 Background 
1.02 
Akili-001 R 
Front-line treatment for ADHD includes the use of stimulant medications , which is 
effective in reducing the core symptoms of the disorder but are associated with 
well-documented side effects. In addition , there is recent evidence that 
pharmacological treatment may not show optimal benefits in some cognitive 
doma ins. (Biederman, J, et al 2015) . Computer ized cognitive train ing programs 
have shown some promise to improve working memory and attention in ADHD 
populations . (Klinberg , T.)1Further research is needed to validate the 
effectiveness of currently available computerized cogn itive interventions as well 
as for consumer -grade gamified therapies that are still being developed . 
This protocol will evaluate the effects of a novel, highly-immersive , videogame-
based interventions for ADHD Project: EVO that was derived from a comparable 
cognitive training program shown to have robust effects on working memory, 
attention , and related constructs in older adults.(Angora, J.A. , et al) EVO 
Multitask incorporates adaptive , simultaneous cognitive tasks into a consumer-
grade action video gaming-like platform with high-quality graphics and reward 
loops, and is deployed on mobile devices (i.e., tablets). We hypothesized that 
EVO Multitask digital therapy would be well-tolerated and feasible to administer 
to pediatric participants with ADHD , and would improve functioning in relevant 
cognitive domains . As a control , this protocol will also evaluate the effects of a 
highly-immers ive educational videogame , "EVO Words " in a matched , time-on-
task manner. 
Novel, cost-effective, and easy to implemenUdissem inate non-pha rmacological 
interventions for ADHD could be helpful for many participants given limitations of 
other approved interventions . 
1.2 Clinical Experience with Study Agent(s) 
Akili has evaluated the EVO Multitask digital therapy in various clinical 
populations as described below. 
Most relevant to the current protocol, a multi-site, open-label, proof-of-
concept study was recently completed in children with ADHD. In this study, 
ADHD (N = 40 , Mean Age = 10.3 years) and age-matched neuro-typical control 
(N =40, Mean Age = 10.5 years) participants were recruited from 3 sites and 
screened for enrollment. A one month , at-home intervention followed , which 
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Akili Interactive Labs, Inc. 
"EVO" Revision 4.3C, ADHD Therapeutic Game 
1.02 
Akili-00IR 
consisted of 5 weekly 30-minute sessions of digital therapy play. Participants 
then returned to the clinic for post-intervention assessment. 
Measures of 
cognitive function (TOVA, CANTAB) and behaviors (Parent-BRIEF) were 
collected at Screening and Post-Intervention . Tolerability, compliance , and 
acceptability were also assessed . No treatment related adverse events were 
reported. The ADHD group completed an average of 81% of the required at-
home sessions , and reported a high level of enjoyment on average. The 
Attention Performance 
Index composite score from the TOVA improved 
significantly from pre-post intervention (p = 0.033, Cohen 's d = 0.35) in the ADHD 
group. There was no change in the neuro-typical group (p = 0.30, Cohen's d = 
0.16). A post-hoc sub-population analysis of a large group of ADHD participants 
with greater cognitive and symptom severity at Baseline (TOVA API <= -1.8 & 
ADHD-RS >=30) showed a larger effect of the intervention (p = 0.003, Cohen's d 
= 0.71). The CANTAB Spatial Working Memory test showed statistically 
significant improvements on 9 of its 19 reported measures for the ADHD group 
while the neuro-typical group improved on 3 of the 19 measures . For the Parent-
BRIEF, the ADHD group showed improvements for working memory, however 
this measure did not meet the alpha criterion for multiple comparisons . No 
change was found for the Parent-BRIEF in the neuro-typical population . Results 
from this proof-of-concept study provide initial support for this novel, consumer-
grade video game intervention as a potential treatment for attention and working 
memory symptoms in pediatric ADHD populations . 
Additional studies using EVO Multitask in related populations include : 
A feasibility study was conducted at a small college for individuals with 
ADHD and other related learning difficulties. Forty-four students with a 
diagnosis of ADHD, ASD, LO (or a combination thereof), were asked to play 
EVO Multitask in their dorm rooms for 30 minutes/day for 1 week. The study 
showed that EVO Multitask was generally engaging and the one week protocol 
was feasible. 
General Results: 
• 
Over the week, participants were able to complete , on average , 25% 
progress through the game (matching the expected pace of 100% 
progress through 4 weeks). 
• 
The participants demonstrated an expected deficit in baseline game 
performance when playing in the multi-task environment as compared to 
single-task , confirming an interference processing deficit. 
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Akili Interactive Labs, Inc. 
"EVO" Revision 4.3C, ADHD Therapeutic Game 
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Akili-00IR 
• 
Over the week protocol, there was significant improvement in subject 
reaction time, as measured in the EVO Multitask program. 
• 
No treatment related adverse events were reported. 
In a pilot study of pediatric sensory processing disorder at the University 
of California, San Francisco {UCSF), 45 children ages 6 to 14 (23 with sensory 
processing disorders / 22 age-matched neuro-typical children) , were asked to 
play EVO Multitask at home for 30 minutes/day , 5 days a week, for 4 weeks. 
Both groups demonstrated that EVO was generally engaging and a 4-week at-
home protocol in these populations was feasible . 
General Results: 
• 
Participants completed, on average, greater than 70% of the game 
sessions. 
• 
Over the first ~1.5 weeks of at-home play, there was improvement (~70 -
150%) in reaction time, as measured in the EVO program. 
• 
No treatment related adverse events were reported . 
In a feasibility study at the Center for Autism Research Disorders {CARD-
ABA Clinic), 10 children with low-functioning autism ages 4 to 14, were 
evaluated for their ability to engage with the EVO Multitask digital therapy during 
an in-clinic visit. Optionally they could take the game home for 1 week of at-
home intervention play. 
General Results: 
• 
Younger participants with more severe ASD were unable to engage with 
EVO Multitask (the digital therapy mechanics and instruction were too 
difficult). 
• 
Two of the older participants with somewhat less impairment took EVO 
Multitask home. These participants completed less than 25% of the game 
over the week, implying that at-home gameplay may not be feasible for 
this population. 
• 
No treatment related adverse events were reported in any of the 
participants. 
Additionally, Akili is currently conducting ongoing research in several additional 
clinical populations including geriatric depressio n, traumatic brain injury, 
Parkinson's disease, cerebrovascular disease , and prodromal Alzheimer's 
disease. To date no treatment related adverse events have been reported. 
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Akili Interactive Labs, Inc. 
"EVO" Revision 4.3C, ADHD Therapeut ic Game 
1.2.2 Rationale 
1.02 
Akili-00IR 
ADHD is one of the most common pediatric psychiatric conditions and best 
practice 
for 
its 
treatment 
includes 
both 
pharmacological 
(usually 
psychostimulants - methylphenidate or amphetamine) and non-pharmacological 
(behavioral or cognitive-behavioral therapy). These treatment modalities have 
demonstrated incontrovertible short-term benefits across core symptoms of 
ADHD and associated impairments. However, there are limitations to current 
best practices for the treatment of ADHD. 
With respect to pharmacological interventions, they are accompanied by adverse 
events in many children, do not normalize functioning , and adherence rates over 
time are generally low. The latter aspect is likely related to the fact that longer-
term benefits of medication for ADHD are modest. Longitudinal studies have 
shown that acute improvements in ADHD symptoms and functioning are not 
maintained beyond 24-36 months. 
With respect to non-pharmacological interventions, access to such services can 
be a challenge for a number of reasons, including the number of qualified 
providers and coverage by third-party payers. 
Given these limitations to current standards of care, there is a strong need for the 
development of additional interventions for ADHD that can be easily and widely 
disseminated. Given the central role of attention and other aspects of cognition in 
the pathophysiology of ADHD, interventions that specifically target these 
constructs in safe and effective ways are particularly needed. 
In recent years, there has been considerable interest in the use of computer-
based software and to improve various aspects of cognition across a range of 
clinical populations, including those with ADHD. The CogMed Working Memory 
Training platform was one of the first interventions in this genre to be explored 
specifically with ADHD and showed promising results in several randomized 
studies. 
Although there are multiple products in the marketplace that make various claims 
about effects on cognition in general, and in some cases, ADHD specifically, 
there have been no large scale, randomized trials of a digital therapeutic 
intervention versus an educational 
control intervention. 
Additionally, no 
approved treatments have been designed to provide an engaging, consumer-
level experience that will promote high compliance when administered remotely 
(i.e., outside of a clinic). 
This study will fill this gap with a large (minimum of 300 participants) randomized 
parallel group, controlled trial. Participants will be randomized (1: 1) to receive 
either the EVO Multitask experimental intervention or the EVO Words 
educational control and instructed to play the digital therapies for typically 25 
minutes/day for 5 days/week over a 4 week treatment period. Change in Baseline 
on the Attention Performance Index from the TOVA 8 will serve as the primary 
outcome variable and will allow for a determination of whether EVO Multitask 
significantly improves attentional functioning in pediatric participants with ADHD. 
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Akili Interactive Labs, Inc. 
1.02 
"EVO" Revision 4.3C, ADHD Therapeutic Game 
Akili-00IR 
Secondary measures will include measures of ADHD symptoms, other measures 
of cognition and executive functioning, and measures of patient and 
parent/caregiver experience and satisfaction. 
The therapeutic play regimen for the current study (typically 25 minutes/day; 5 
days/week; 4 weeks) was established based on previous work with the EVO 
Multitask digital therapy. Specifically, a proof-of-concept study demonstrated that 
this regimen resulted in significant improvements in API scores in a sample of 
children with similar characteristics as proposed for this study. Results from the 
current study may also inform the development of additional dose-finding studies 
to determine whether additional (or less) game play might yield different results. 
It will also form the basis of additional studies to examine the durability of the 
intervention over time. 
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Akili Interactive Labs, Inc. 
"EVO" Revision 4.3C, ADHD Therapeutic Game 
2. OBJECTIVES 
1.02 
Akili-00 IR 
To evaluate the effects of EVO Multitask game-based digital therapy versus EVO 
Words game-based digital therapy on attentional functioning (measured by the 
TOVA), ADHD 
symptoms, 
cognitive/executive 
functioning, and 
clinical 
impairment, in children diagnosed with ADHD. 
2.1 Primary Obiective 
To evaluate the effects of EVO Multitask play versus EVO Words play on 
attentional functioning (measured by the API change score from the TOVA 8). 
2.2 Secondary Obiectives 
To evaluate the effects of EVO Multitask play versus EVO Words play on ADHD 
symptoms (measured via a clinician and parent rating scales of ADHD 
symptoms) 
To evaluate the effects of EVO Multitask play versus EVO Words play on 
objective working memory as measured by the CANTAB Spatial Working 
Memory (SWM) computerized test. 
To evaluate the effects of EVO Multitask play versus EVO Words play on 
objective inhibition as measures by the TOVA commission error standard score 
in TOVA half-2. 
2.3 Exploratory & Descriptive Obiectives 
To explore the percentage of responders (defined in the Statistical Analysis Plan) 
to primary and secondary objectives along with descriptive analysis of 
child/parent surveys, treatment regimen compliance, demographics, secondary 
symptom / executive function measures adjusted for baseline parent expectation, 
and any resulting treatment related AEs. In addition multiple sensitivity analyses 
will be conducted to assess the effects of site poolability, age, gender, missing 
data (if appropriate), and baseline TOVA API. 
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Akili Interactive Labs, Inc. 
"EVO" Revision 4.3C, ADHD Therapeut ic Game 
3. SUBJECT SELECTION 
3.1 Inclusion Criteria 
1.02 
Akili-00IR 
To be eligible for this trial, participants must meet all of the following criteria: 
1. Age 8 years to 12 years, inclusive, at the time of parental informed 
consent 
2. Male or female 
3. Confirmed ADHD diagnosis , any presentation , at Screening based on 
DSM-V criteria and established via the MINI-KID administered by a 
trained clinician 
4. Screening/Baseline (Visit 1 or 1 a) score on the clinician-rated ADHD-
RS-IV score 
28 
5. Screening/Baseline (Visit 1 or 1a) score on the TOVA API 
-1.8 
6. Not undergoing pharmacological treatment with methylphenidate or 
amphetamine-based products at time of Screening ; or, if undergoing 
pharmacolog ical treatment , must be willing and appropriate (i.e. not 
optimally treated in the investigator's judgment) to wash out of current 
regimen. 
7. Ability to follow written and verbal instructions (English), as assessed 
by the Pl and/or study coordinator 
8. Estimated IQ score~ 80 as assessed by the Kaufmann Brief 
Intelligence Test, Second Edition (KBIT-II) 
9. Ability to comply with all the testing and requirements. 
3.2 Exclusion Criteria 
If a subject meets any of the following criteria , he or she may not be enrolled in 
the study: 
1. Current, controlled (requiring a restricted medicatio n) or uncontrolled, 
comorbid psychiatric diagnosis , based on MINI-KID and subsequent 
clinical interviewing, with significant symptoms including but not 
limited to post-traumatic stress disorder , psychosis, bipolar illness, 
pervasive developmental disorder, severe obsessive compulsive 
disorder, severe depressive or severe anxiety disorder , conduct 
disorder , or other symptomatic manifestatio ns that in the opinion of 
the Investigator may confound study data/assessments . Participants 
with clinical history of learning disorders will be allowed to participate, 
provided the disorder does not impact their ability to participate in the 
trial based on Pl judgment 
2. Participants who are currently treated with a non-stimulant medication 
for ADHD (i.e., atomoxetine , clonidine, guanfac ine) 
3. Initiation within the last 4 weeks of behavioral therapy . Participants 
who have been in behavior therapy consistently for more than 4 
Confidential 
weeks may participate provided their routine is unchanged during the 
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Akili Interactive Labs, Inc. 
1.02 
"EVO" Revision 4.3C, ADHD Therapeutic Game 
Akili-00 IR 
course of the study. Participants planning on changing or initiating 
behavior therapy during the course of the study will be excluded . 
4. Participant is currently considered a suicide risk in the opinion of the 
Investigator , has previously made a suicide attempt , or has a prior 
history of, or is currently demonstrat ing active suicidal ideation or self-
injurious behavior as measured by C-SSRS at screening . 
5. Motor condition (e.g., physical deformity of the hands/arms ; 
prostheses) that prevents playing the digital therapy as reported by 
the parent or observed by the investigator . 
6. Recent history (within the past 6 months) of suspected substance 
abuse or dependence. 
7. History of seizures (exclusive of febr ile seizures) , or significant motor 
or vocal tics, including but not limited to Tourette 's Disorder. 
8. Has participated in a clinical trial within 90 days prior to screen ing. 
9. Diagnosis of or parent-reported color blindness (Confirmed in-clinic 
via ICBT) 
10. Uncorrected visual acuity (Confirmed in-clinic via ability of subject to 
play the game) 
11. Regular use of psychoactive drugs (non-stimulant) that in the opinion 
of the Investigator may confound study data/assessments . 
12.Any other medical condition that in the opinion of the investigato r may 
confound study data/assessments. 
13. Has a sibling also enrolled/currently participating in the same study 
14. Has previously participated in a study of Akili's videogame -like digital 
therapy 
3.3 Concomitant Medications and Treatment 
1. With the exception of common over the counter (OTC) (e.g. ibuprofen, 
acetam inophen) and prescription medications (e.g. antibiotics) for 
minor transient ailments , regular use of concomitant medications (i.e., 
sleep aids, etc.) are not permitted during the study . Section 6 lists 
allowed and prohibited medications . Transient use of some 
medications (i.e., non-sedat ing antihistamines to treat seasona l 
allergies) may be permitted on a case-by-case basis with Pl and 
medical monitor review/approval. Families should advise the study 
staff if it becomes necessary to use other types of medication . Study 
investigators can approve short-term use of other medications that are 
not anticipated to confound study assessments . 
2. Initiation of or significant changes in non-pharmacologica l treatment for 
ADHD is not permitted during the course of the study. Participants 
actively engaged in non-pharmacolog ical treatment at Screening, may 
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Akili Interactive Labs, Inc. 
1.02 
"EVO" Revision 4.3C, ADHD Therapeutic Game 
Akili-00IR 
be eligible if they meet all inclusion criteria and do not undergo 
changes to their treatment during the course of the study. 
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1.02 /4-Aug- l 6 
24 

Akili Interactive Labs, Inc. 
"EVO" Revision 4.3C, ADHD Therapeutic Game 
4. STUDY DESIGN 
4.1. OVERVIEW OF STUDY 
1.02 
Akili-00IR 
The study will be a blinded (investigators and outcome assessors) randomized, 
parallel group, controlled trial of EVO Multitasking game-based digital therapy 
versus EVO Words game-based digital therapy. 
The trial will consist of 3 primary phases: Screening, Washout/Baseline, and 
Treatment. During the Screening Phase (Day -28 to Day -7), participants will 
undergo screening to evaluate eligibility for the study. Screening may take place 
up to 28 days before the Baseline Visit (Day 0). For those children currently on 
medication for ADHD the Washout period will begin 7 days prior to Baseline 
where treatment will be discontinued. On Day 0, the Baseline visit will occur 
wherein additional eligibility criteria will be established (ADHD-RS scores and 
API scores). The Treatment Phase (Day 1 to Day 27) will involve playing the 
digital therapy at home for each participant followed by an In-Clinic assessment 
on Day 28 to assess key outcomes. Compliance with play requirements will be 
monitored remotely during this phase. 
Participants for this study will be male and female children between the ages of 8 
years, 0 months and 12 years 11 months at the time of consent who meet full 
criteria for ADHD, any subtype, as assessed by the MINI-KID. Children must also 
be medically healthy, willing to discontinue any ongoing treatment, and free from 
other significant psychiatric comorbidities. 
Two different electronically administered digital therapies will comprise the 
treatments under study: 
Treatment #1 will consist of Project: EVO Mobile Game-Based Digital Therapy 
Intervention (EVO Multitasking therapy), a proprietary system based on a 
prototype cognitive training videogame called Neuroracer. EVO Multitasking 
digital therapy was designed to incorporate the fundamental features of 
Neuroracer into 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. EVO 
Multitasking therapy employs a 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 multi-task training regimen is 
automatically configured and delivered to the user, and is optimized adaptively to 
increase multi-task performance. 
As players proceed through the therapy 
periodic re-calibration occurs to maintain an optimal difficulty level. 
Treatment #2 will consist of the EVO Words Mobile Game-Based Digital-Therapy 
Intervention (EVO Words Therapy), which is based off a popular Brain Training 
25 
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Akili Interactive Labs, Inc. 
"EVO" Revision 4.3C, ADHD Therapeutic Game 
1.02 
Akili-OOIR 
app available in the iTunes app store: In the game, the player spells as many 
words as possible by connecting letters on a grid. He or she can connect the 
letters in any direction by touching the starting square and dragging his or her 
finger along the desired path. Each word created scores points for the 
player. Longer words and use of unusual letters increases the score of a 
word. Once the player can no longer find new words on the grid, the player can 
generate a new grid by pressing a "shuffle" button. The "shuffle" button deducts 
points from the players score. EVO Words contains 12 levels. As the levels 
increase, the size of the grid decreases. The goal of the game is to accumulate 
as many points as possible. 
For each intervention condition, treatment will involve game-play on the system 
for approximately 25 minutes/day at least 5 days a week, for a total of 8 hours 
and 20 minutes of total game play. Compliance will be monitored electronically. 
The primary endpoint for the study will be between-group comparison of the 
difference between the Baseline (Day 0) and Endpoint (Day 28) measure of the 
API score from the TOVA 8. 
Figure 1 below provides an overview of the study design and assessments. 
Study Doy O (untreotH children} 
Study Doy-7 to .3 (stimulant 
Study Doy O (stimulant treated chlldren} 
treated chlldren) 
VIIIU 
I -----------------------
! 
I 
Baseline Visit la 
RANOOMllATION (1:1) 
Study Days 1-27 
EVO Multltask Therapy 
EVO Words Therapy 
Dru1 Washout for <Nldren 
tre~ed wtth stimulants at 
ScrHnlns; Must be minimum of 
3 cloys 
Figure 1. Study Schematic. 
4.2 Treatment Arms 
Study Doy 28 (+3 days) 
~of 
lllllly 
Vlllt2 
Each of the two treatment arms for the study, EVO Multitasking therapy and EVO 
Words therapy will be administered in similar format via a standardized tablet 
(i.e., iPad) provided to participants by the sponsor. The visual layout (i.e., color 
scheme) will be similar for each of the two interventions. The content of the two 
interventions will be different. EVO Multitasking will involve a character moving 
through a game-like space, while the EVO Words will involve letters and a grid as 
described above 
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Akili Interactive Labs, Inc. 
"EVO" Revision 4.3C, ADHD Therapeutic Game 
PERIOD 
Visit 
Day 
Informed consent and child assent 
Demographic & contact information 
Developmental & Medical History 
MINI-KID 
Kaufmann Brief Intelligence Test, Second 
Edition 
C-SSRS assessment 
Ishihara Color Blindness Test 
Discontinue Medication 
TOVA assessment 
CANT AB Spatial Working Memory 
ADHD-RS 
Parent BRIEF 
Impairment Rating Scale 
Clinical Global Impressions Scaleb 
Randomization 
EVO Multitasking intervention or EVO 
Words intervention in-clinic assessment 
(+Parent Expectation Survey) 
At-home EVO Multitasking intervention or 
EVO Words intervention play 
Screening/Baseline• 
1 
1.02 
Akili-00IR 
0 or up to 7 days prior to Baseline for those 
children requiring washout 
X 
X 
X 
X 
X 
X 
X 
Xd 
Xd 
Xd 
Xd 
xd 
xd 
xd 
Xd 
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1.02 /4-Aug- I 6 
Washout' 
Baseline• 
Stimulant washout 
group only 
XC 
1a 
0 
x-
x-
x-
x-
x-
x-
x-
x-
At-Home 
Intervention 
1 - 27 
X 
Post-
Treatment 
Visit 
2 
28 
X 
X 
X 
X 
X 
X 
X 
27 

Akili Interactiv e Labs, lnc. 
"EVO" Revision 4.3C, ADHD Therapeutic Game 
Optional weekly performance report to 
parents 
Compliance monitoring and feedback' 
Patient Experience/Satisfaction Measure-
Parent Version 
Patient Experience/Satisfaction Measure-
Child Version 
Safety assessments /AEs and 
concomitant medication I therapy 
Collect iPads & Return to Akili for erasing 
X 
1.02 
Akili-OOIR 
X 
X 
X 
X 
X 
X 
X 
xg 
8Participants who are not currently on ADHD medications at Screening will have a combined Screening/Baseline visit where all measures are completed. For participants currently 
treated with stimulant medications and who are eligible to initiate a washout period , a separate Baseline visit will be scheduled 3-7 days after Screening where the addit ional 
measures will be completed . 
bFor CGI measure, CGI Severity Scale will be assessed at Screening and CGl-lmprovement Scale will be assessed at the Follow-Up Visit. 
"To be initiated for participants who are currently treated with psychostimulants for ADHD at Screening ; and for whom study participation is still indicated based on procedures 
described in Section 4.5. Washout should be scheduled at Screening visit and overseen by a qualified provider at each study site. 
dFor children currently not treated with stimulant medication , these procedures will occur at Visit 1. 
9For children currently treated with stimulant medication who are eligible to continue following a washout of medication , these procedures will occur at Visit 1 a. 
'compliance with intervention play requirements will be monitored via automatic uploading of play information to DCRI and a daily email report to DCRI and the clinical sites from the 
sponsor or their designated representative . The sites will provide feedback to the parents (via a pre-established contact method and will indicate when play drops below the 
minimum requirements. 
gSites are required to return the device to Akili for complete erasing of all data entered prior to re-circulation of the device . This process must be documented on the iPad 
Accountability Log. 
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28 

Akili Interactive Labs, Inc. 
"EVO" Revision 4.3C, ADHD Therapeut ic Game 
4.3 Screening/Baseline Procedures 
1.02 
Akili-00IR 
At the Screening/Baseline Visit (Visit 1) participants' parents or legal caregivers 
will be asked to provide informed consent; children will provide assent that will be 
documented appropriately. Participants and their parents/caregivers will then 
undergo a comprehensive evaluation to determine eligibility and whether 
inclusion/exclusion criteria are met. All of the following assessments will be 
recorded in the CRF if the subject is recruited into the study. Medical and 
psychiatric history, and demographic information will be obtained. 
Current 
medications and those taken during the past 30 days. Lifetime history of ADHD 
treatments taken will be obtained. The Kaufman Brief Intelligence Test, Second 
Edition will be administered to children and they must score .::. 80 to continue in 
the study. The MINI-KID , a semi-structured interview, will be administered by 
qualified and trained clinicians to confirm ADHD diagnosis and determine 
whether psychiatric comorbidities are present. 
The C-SSRS, CGI-Severity, 
Ishihara Color Blindness Test, Impairment Rating Scale will then be completed. 
Ongoing medical issues will be assessed. Participants 
Specific Procedures to be completed at the Screening/Baseline Visit (Visit 1) for 
all participants include: 
• 
Informed consent with parent/caregiver; assent with child 
• 
Demographic and Family information: 
Age and gender should be 
recorded in the screening log and the full demographics should be 
recorded in the CRF. 
• 
Developmental and Medical History: Should be recorded in the screening 
log and in the CRF. 
• 
MINI-KID completed by a trained clinician: Should be recorded in the 
screening log and in the CRF. 
• 
C-SSRS (Lifetime): Should be recorded in the screening log and in the 
CRF. 
• 
Ishihara Color Blindness Test: Should be recorded in the screening log 
and in the CRF. 
• 
Kaufman Brief Intelligence Scale, Second Edition: Age-adjusted raw 
scores and percentiles for Matrices, Vocabulary, and Composite should be 
recorded in the screening log and in the CRF. 
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Akili Interactive Labs, Inc. 
"EVO" Revision 4.3C, ADHD Therapeutic Game 
1.02 
Akili-00IR 
• 
Assessment of Ongoing Medical Issues/Concomitant Treatments: Should 
be recorded in the CRF. 
Note that the following procedures will take place at the Screening/Baseline Visit 
(Visit 1) ONLY FOR THOSE PARTICIPANTS WHO ARE NOT CURRENTLY 
TREATED WITH PSYCHOSTIMULANTS: 
The child will complete the following procedures: 
• 
TOVA; Child must score ~-1.8 on the API to remain eligible: The TOVA 
test will take approximately 25 minutes to complete. Separate instructions 
will be provided to the blinded raters to administer this test and to 
download and save the test results. The TOVA API score should be 
recorded in the CRF. 
• 
CANT AB Spatial Working Memory task: The CANT AB SWM task will take 
approximately 9 minutes to complete. 
Separate instructions will be 
provided to the blinded raters to administer this test and to download and 
save the test results 
While the child completes the TOVA and CANTAB, parents will complete the 
following procedures: 
• 
Clinician completed ADHD-RS; must score ~28 to remain eligible: The 
results of the ADHD-RS should be recorded in the CRF. 
• 
Parent-Completed BRIEF: The parents should be instructed by a blinded 
rater to focus their evaluation over their child's past week behavior. The 
BRIEF Raw, T, o/oile, negativity, and inconsistency scores should be 
recorded in the CRF. 
• 
Impairment Rating Scale: 
A blinded clinical rater will review the 
Impairment Rating Scale with the parent. The results of the Impairment 
Rating Scale should be recorded in the CRF. Note that this scale was 
developed as a parent-reported instrument and severity ratings are often 
made via a visual analog scale. For the current protocol, the blinded 
clinical rater should solicit information about the areas of impairment for 
each subject and, using their clinical judgment , rate the severity of the 
impairment across functional domains on a 7 point scale. 
• 
CGI-Severity Scale. A blinded rater will complete the CGI-Severity scale 
based on all available information. The results of the CGI-Severity scale 
should be recorded in the CRF. 
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Akili lnteractive Labs, lnc. 
1.02 
"EVO" Revision 4 .3C , ADHD Therapeutic Game 
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• 
Randomization: The participants will be provided with an iPad which is 
engraved in the back with a serial number ("AL-###"). The iPads will be 
preloaded with either EVO Multitasking therapy or EVO Words therapy. A 
separate document will list the blinded treatment assignment. 
• 
Break: Participants should be allowed a 10 minute break following the 
TOVA/ CANTAB tests. During the break they may have a snack but no 
caffeinated beverages are allowed 
• 
In-Clinic Assessment/Training for EVO Multitasking therapy OR EVO 
Words therapy (depending upon randomization). The subject will only 
practice on the therapy to which they were randomized. The subject 
should play either EVO Multitask or Words for approximately 10 minutes. 
(Note: The parents should observe their child interact with the therapy as 
they will be asked to rate their expectations of possible benefit). Separate 
instructions will be provided to an unblinded clinical coordinator to log the 
subject into either the EVO or Words therapy. During the 10 minutes of in-
clinic play, the unblinded coordinator should observe the participants play 
to ensure he or she can follow the rules (which are in English) of their 
assigned therapy. The unblinded coordinator should also make note of 
any motor conditions or uncorrected visual acuity that prevents proper 
game play. Participants that are unable to properly play their therapy will 
be withdrawn from the study. 
Note: 
For EVO Words the participant 
should be able to spell at least two words during the assessment. At the 
end of approximately 10 minutes the unblinded coordinator should have 
the subject stop his/her play (at an obvious break point in the game) and 
turn the iPad off. At this point, the parent should complete the Baseline 
Expectation Survey 
• 
Materials to go home: 
An unblinded coordinator should provide the 
parents with of a copy of their ICF and child assent along with the 
instructions for their child's therapy. The parents should be told that their 
child is expected to play their therapy for typically 25 minutes/day, 5 
days/week. NOTE: The parent and child should be told that no one 
except the child may play the therapy for any reason. 
The child 
should be provided with same iPad they previously played in the clinic 
along with a battery charger. In addition, both parent and participant 
should be instruction on intended and unintended use of the device. 
These are defined as: 
• 
Intended use- Set up of the participant's local WiFi network 
for internet access to push play and compliance data to the 
Akili secure severs, and completion of at-home interventional 
play for the assigned 25 minutes per day, during 5 days of 
each calendar week. 
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Akili Interactive Labs, Inc. 
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"EVO" Revision 4.3C, ADHD Therapeutic Game 
Akili -00 IR 
• 
Unintended use - Any and all other features or applications 
of the device, including accessing the internet, downloading 
of additional applications, use of features such as music, 
calendar, or notes, and inputting any personal information 
other than participant's home WiFi network as described 
above. 
4.4 Washout Procedures & Screening/Baseline (Post Washout) Procedures 
For participants who are currently treated with psychostimulants for ADHD 
and are still eligible to continue in the trial following Screening, procedures for 
washout and Baseline will be discussed with the parents/caregivers. 
Qualifications for treated participants to enroll in trial: Participants who meet full 
criteria for ADHD at Screening based on the MINI-KID, and who the Pl believes 
are not optimally treated with current medication will be eligible to washout of 
their current medication regimen and enroll in the trial. Suboptimal response to 
current treatment may be assessed by the Pl on the basis of MINI-KID symptom 
presentation and CGI-Severity scores that are 3 (minimally impaired) or higher. 
For those participants eligible to enroll and initiate washout of their current 
medication, treatment will be discontinued between 7 and 3 days prior to their 
scheduled Screening/Baseline Visit (Visit 1a). Study staff will be available via 
phone or unscheduled visit during this period should clinical issues rise that 
warrant attention. 
Note that the following procedures will take place at the Screening/Baseline (Visit 
1 a) 
ONLY 
FOR 
THOSE 
PARTICIPANTS 
WHO 
WASHED 
OUT/ 
DISCONTINUED PSYCHOSTIMULANTS. Following their washout period, during 
Visit 1 a, the child will complete the following procedures: 
• 
TOVA; Child must score ~-1.8 on the API to remain eligible. The TOVA 
test will take approximately 25 minutes to complete. Separate instructions 
will be provided to the blinded raters to administer this test and to 
download and save the test results. The TOVA API score should be 
recorded in the CRF. 
• 
CANT AB Spatial Working Memory task: The CANT AB SWM task will take 
approximately 9 minutes to complete. 
Separate instructions will be 
provided to the blinded raters to administer this test and to download and 
save the test results 
While the child completes the TOVA and CANTAB, parents will complete the 
following procedures: 
• 
Clinician completed ADHD-RS; must score :=_28 to remain eligible: The 
results of the ADHD-RS should be recorded in the CRF. 
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Akili Interactive Labs, Inc. 
1.02 
"EVO" Revision 4.3C, ADHD Therapeutic Game 
Akili-00 IR 
• 
Parent-Completed BRIEF: The parents should be instructed by a blinded 
rater to focus their evaluation over their child's past week behavior The 
BRIEF Raw, T, o/oile, negativity, and inconsistency scores should be 
recorded in the CRF. 
• 
Impairment Rating Scale: 
A blinded clinical rater will review the 
Impairment Rating Scale with the parent. The results of the Impairment 
rating Scale should be recorded in the CRF. Note that this scale was 
developed as a parent-reported instrument and severity ratings are often 
made via a visual analog scale. For the current protocol, the blinded 
clinical rater should solicit information about the areas of impairment for 
each subject and, using their clinical judgment , rate the severity of the 
impairment across functional domains on a 7 point scale. 
• 
CGI-Severity Scale. A blinded rater will complete the CGI-Severity scale 
based on all available information. The results of the CGI-Severity scale 
should be recorded in the CRF 
• 
Randomization: The participants will be provided with an iPad which is 
engraved in the back with a serial number ("AL-###-"). The iPads will be 
preloaded with either EVO Multitasking therapy or EVO Words therapy. A 
separate document will list the blinded treatment assignment. 
• 
Break: Participants should be allowed a 10 minute break following the 
TOVA/ CANTAB tests. During the break they may have a snack but no 
caffeinated beverages are allowed 
• 
In-Clinic Assessment/Training for EVO Multitasking therapy OR EVO 
Words therapy (depending upon randomization): The subject should play: 
either EVO Multitask or EVO Words for approximately 10 minutes. (Note: 
The parents should observe their child interact with the therapy as they 
will be asked to rate their expectations of possible benefit). 
Separate 
instructions will be provided to an unblinded clinical coordinator to log the 
subject into either the EVO Multitask or EVO Words therapy. During the 
10 minutes of in-clinic play, the un-blinded coordinator should observe the 
participants play to ensure he or she can follow the rules (which are in 
English) of their assigned game. The un-blinded coordinator should also 
make note of any motor conditions or uncorrected visual acuity that 
prevents proper game play. Participants that are unable to properly play 
their therapy will be withdrawn from the study. Note: For EVO Words the 
participant should be able to spell at least two words during the 
assessment. 
At the end of approximately 10 minutes the unblinded 
coordinator should have the subject stop his/her play (at an obvious break 
point in the game) and turn the iPad off. At this point, the parent should 
complete the Baseline Expectation Survey 
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• 
Materials to go home: 
An un-blinded coordinator should provide the 
parents with of a copy of their ICF and child assent along with the 
instructions for their child's therapy. The parents should be told that their 
child is expected to play their therapy for typically 25 minutes/day, 5 
days/week. NOTE: The parent and child should be told that no one 
except the child may play the game for any reason. The child should 
be provided with same iPad they previously played in the clinic along with 
a battery charger. In addition, both parent and participant should be 
instructed on intended and unintended use of the device. These are 
defined as: 
• 
Intended use- Set up of the participant's local WiFi network 
for internet access to push play and compliance data to the 
Akili secure severs, and completion of at-home interventional 
play for the assigned 25 minutes per day, during 5 days of 
each calendar week. 
Unintended use - Any and all other features or applications 
of the device, including accessing the internet, downloading 
of additional applications, use of features such as music, 
calendar, or notes, and inputting any personal information 
other than participant's home Wi-Fi network as described 
above. 
4.5Treatment Procedures - In-Home Game Play and Post-Treatment Visit 
Beginning on the first day after the Screening/Baseline Visit (Visit 1 for untreated 
children at Screening; Visit 1a for those children requiring medication washout), 
participants will initiate at-home play with their randomized therapy (EVO 
Multitasking or EVO Words). The therapy will pick up from where it left off during 
the in-clinic session. Participants and their parents will be instructed during 
Screening and Baseline that the expectations for play will be typically 25 
minutes/day, 5 days/week. 
For each play episode, participants will logon to their assigned iPad with a unique 
ID and initiate therapeutic play. Log on passwords and game instructions will be 
provided separately. Details about performance and duration of play will be 
recorded and uploaded to central servers (when the iPad is connected to Wi-Fi) 
for data capture. Compliance with therapy play requirements will be monitored 
automatically and sites will receive daily email notifications. For participants not 
meeting the requirements, email reminders and instructions will be provided. 
Additionally, EVO Multitasking and EVO Words both contain built-in features that 
remind the participant to play. Participants who fail to meet play requirements 
will be contacted by an un-blinded site clinical coordinator to troubleshoot 
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problems and problem-solve to increase compliance (Scripts for these 
communications will be described in a separate document). 
During the 
demographic data collection, the parent should specify the preferred method by 
which they would like to be contacted (e.g. phone, text, or email). Additionally 
parents will receive a weekly and automatically generated progress email report 
directly from the Sponsor (Akili) by sharing their email at informed consent. 
However, parents may elect to opt-out at the time of informed consent. 
On day 21 the study site should remind the parents by phone, preferably (email 
and/or text are also acceptable) , that their child is entering the last week of the 
study (A script for this communication will be described in a separate document) . 
The post-treatment visit (Visit 2 will be scheduled to occur 4 weeks after the 
Baseline Visit. If the parent and child are unable to return to the clinic on Day 28, 
Day 28 + 3 days is acceptable (the subject should be encouraged to continue to 
play their therapy during this exception period). Children who have been ill or 
taken medication within 48 hours of their scheduled Visit 2 should contact DCRI 
CRA and the medical monitor to advise regarding scheduling, In general, 
participants should not be scheduled for their Visit 2 if they have been sick 
enough to skip school, or if they have taken any medications that may have 
impacted functioning within 48 hours. 
At this visit, participants will be re-
assessed for attentional functioning , ADHD symptoms , and impairment. 
Additional information regarding satisfaction and experience with the therapy will 
be collected from both participants and their parents/caregivers . 
NOTE: The parent and subject should return to the clinic at approximately the 
same time of day (i.e. morning or afternoon) as was done for the 
Screening/Baseline Visit (Visit 1 or 1 a for untreated or treated children, 
respectively). Assessments should also be administered in the same order per 
the Table of Procedures in Section 4.3. Also , all attempts should be made to 
ensure that the same parent/caregiver accompany the subject and complete the 
outcome measures. Also, all attempts should be made to ensure that the same 
study staff administers the subjective clinical outcome measures (ADHD-RS, 
CGI, and IRS). 
Specific procedures to be completed during the Post-Treatment Visit include: 
• 
C-SSRS (Since last visit): The results of the C-SSRS should be recorded 
in the CRF 
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• 
Clinician completed ADHD-RS: 
recorded in the CRF 
Results of the ADHD-RS should be 
• 
Clinician Completed CGI Improvement Scale. The results of the CGI 
Improvement Scale should be recorded in the CRF 
• 
Impairment Rating Scale. The results of the Impairment Rating Scale 
should be recorded in the CRF 
• 
TOVA: The TOVA test will take approximately 25 minutes to complete. 
Separate instructions will be provided to the blinded raters to administer 
this test and to download and save the test results The TOVA API score 
should be recorded in the CRF. 
• 
CANT AB Spatial Working Memory task: The CANT AB SWM task will take 
approximately 9 minutes to complete. 
Separate instructions will be 
provided to the blinded raters to administer this test and to download and 
save the test results 
• 
Parent-Completed BRIEF: While the subject is performing the CANTAB 
SWM and TOVA, the parents will be asked to complete the BRIEF. The 
parents should be instructed by a blinded rater to focus their evaluation 
over their child's past week behavior. The BRIEF Raw, T, %ile, negativity, 
and inconsistency scores should be recorded in the CRF 
• 
Patient Experience/Satisfaction Measure -
Parent Version: 
The un-
blinded rater will complete a parent survey. The results will be captured in 
the CRF 
• 
Patient Experience/Satisfaction Measure - Child Version: The un-blinded 
rater will compete a child survey. The results will be captured in the CRF. 
• 
Assessment of Adverse Events/Concomitant Treatment: AEs and Con-
Meds will be captured in the CRF 
• 
The iPad and battery charger will be returned to site 
• 
Prior to re-circulation of the device to future participants, the device will be 
returned to Akili for complete erasing of all data entered by the participant. 
4.6 Procedures to minimize bias and blinding to treatment assignment 
Participants and their parents will not be aware of which of the interventions to be 
used in the study is the test device and which is the comparator. The clinicians 
and staff completing assessments will be blinded to which device each 
participant is assigned. An un-blinded staff member at each site will be 
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designated 
in 
order 
to 
provide 
initial 
instructions 
for 
use 
at 
the 
Screening/Baseline Visit, monitor compliance, and follow up with parents as 
required. Parents and participants will be instructed not to share instructions 
about the details of the intervention to which they were assigned to the study 
staff during their subsequent End of Treatment visit (Visit 2).). Additional details 
around the procedures to be used to minimize bias and blind participants/parents 
and site staff are as follows. 
Since the EVO Multitasking therapy and the EVO Words therapy are 
fundamentally different, true blinding is not possible for this study. The following 
study procedures will be implemented to maximize the chances that 1) 
participants and their parents are not aware of which treatment condition is the 
test intervention and which is the comparator; and 2) that site staff involved in 
completing outcome measures are blinded to treatment assignment. 
4.6.1 Procedures to minimize bias in parents and participants. 
All communication between site staff and participants/parents should 
emphasize that this is a study to evaluate the effects of 2 different 
therapies on ADHD symptoms. This communication should be reviewed in 
the consent procedures. If parents raise questions about whether 1 of the 
treatments is expected to have a different effect, they should be informed 
that the study is designed to evaluate how they compare to one another 
on ADHD functioning. During Screening/Baseline, participants/parents will 
be reminded not to discuss the details or content of their assigned 
treatment with anyone at the site other than the un-blinded coordinator 
who will review the instructions for the randomized therapy with each 
participant. Participants/parent will also be discouraged from discussing 
the details/content of their assigned therapy with other children/families 
outside of the study. 
4.6.2 Procedures to blind/minimize bias in site staff and investigators.:. 
Following Screening and prior to randomization, investigators and site 
staff will remind participants/parents not to discuss the content/details of 
their assigned treatment with anyone at the site except the un-blinded 
coordinator. Upon returning to the clinical site for their Baseline 1 a visit 
(for participants who require washout) and for their follow-up (Visit 2) visit, 
participants and their families will be reminded not to discuss the 
content/details of their assigned treatment with other site staff. Following 
randomization at the end of Visit 1 (or Visit 1a for participants requiring 
washout), participants/parents will only have direct contact with the 
unblinded coordinator who will review instructions for their assigned 
treatment condition. Participants/parents will be reminded not to discuss 
the content/details of their assigned treatment in the event of any phone 
calls or unscheduled visits that might occur prior to the Visit 2. 
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Investigators and other blinded site staff will not have access to any 
source documents or CRFs that may compromise the blind. 
4.6.3 Procedures in the event of possible or probable unblinding. 
If at any point after randomization an Investigator or other site staff 
responsible for completing any of the outcome measures becomes 
possibly or probably un-blinded, the following procedures should be 
implemented: 
• 
A description of the un-blinding event should be generated and 
sent to the DCRI Coordinating Pl (Kollins), Medical Monitor 
(Krystal) and Project Leader. 
• 
If there are still study assessments that need to be completed, an 
alternative and blinded rater should be used, if available at the site 
(e.g., a Sub-I) 
• 
If a blinded Sub-I or other trained and qualified blinded rater is not 
available, the measures should be completed by the unblinded 
rater. 
Note: In the event of unblinding as described above or if study staff 
explicitly unblinds the parent or participant to the study hypothesis, the 
unblinding event will be noted in the CRF. 
4.8 Randomization Procedures 
Participants who meet all inclusion/exclus ion criteria and sign the informed 
consent/assent will be enrolled. Randomization will occur during the baseline visit 
only after ADHD diagnosis is confirmed via the MINI-Kid. The treatment given to 
individual participants will be determined by a randomization schedule will be 
generated by the scheme prepared by Duke Clinical Research Institute (DCRI) 
statistics group using a validated computer software (SAS) that incorporates a 
standard procedure for generating random numbers. A copy of the randomization 
schedule scheme will be held by the DCRI Statistics Department. The 
randomization scheme will be monitored monthly through the enrollment period 
for accuracy. This schedule will be loaded into the clinical database 
randomization module. Participants randomized into the study will be assigned 
the treatment corresponding to the next available number in the randomization 
schedule. Any participants that show non-compliance as described in Section 
8.5.1 will be replaced. 
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Participants will be randomized in a 1: 1 ratio to receive either an iPad preloaded 
with EVO Multitasking therapy or an iPad preloaded with EVO Words therapy. 
Randomization will be stratified by drug washout or no drug washout. Group #1 -
washed out of stimulant (at time of informed consent) and group #2 - wasn't on 
stimulant (at time of informed consent). Although no official gender stratification 
is indicated, study sites will use their best efforts to gender-match and enroll a 
minimum of 30% girls. 
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5 STUDY DEVICE 
1.02 
Akili-001 R 
The study devices are NOT intended to be used for any purpose other than that 
outlined in this protocol. 
Description of Study Device (EVO Multitasking therapy): EVO Multitasking 
therapy will be loaded by the sponsor (Akili) onto iPad Mini II tablets. The iPads 
are configured to minimize the participants' ability to utilize non-study related 
applications. Features such as browsing the internet, downloading apps, deleting 
apps, and messaging are restricted. However, some functions such as Music 
(which may provide for downloading via iTunes}, Notes, Calendar, and 
Reminders may potentially be accessed by participants. Unblinded site staff will 
instruct participants and parents on intended and unintended use, as outlined in 
this protocol. The iPads along with chargers will be provided by the sponsor to 
the clinical sites. In a separate document, a list of logon credential (Subject IDs 
and Passwords) will be provided. All data entered by the participant onto the 
device will be erased before reusing the device. 
Description of Study Device (EVO Words therapy): EVO Words therapy will be 
loaded by the sponsor (Akili) onto iPad Mini II tablets. The iPads are configured 
to minimize the participants' ability to utilize non-study related applications. 
Features such as browsing internet, downloading apps, deleting apps, and 
messaging are restricted. However, some functions such as Music (which may 
provide for downloading via iTunes), Notes, Calendar, and Reminders may 
potentially be accessed by participants. Unblinded site staff will instruct 
participants and parents on intended and unintended use, as outlined in this 
protocol. The iPads along with chargers will be provided by the sponsor to the 
clinical sites. In a separate document, a list of logon credential (Subject IDs and 
Passwords) will be provided. All data entered by the participant onto the device 
will be erased before reusing the device. 
5.1 Study Device Usage 
Participants and their parents/caregivers will be instructed to play their assigned 
therapy for a duration of typically 25 minutes/day for 5 days/week during each of 
the 4 weeks of the treatment phase of the study. For EVO Multitask 25 
minutes/day is accomplished by playing 5 "sessions" of 4 to 5 minutes each. For 
EVO Words 25 minutes/day is accomplished via a displayed minute timer. 
Participants should initiate play on the first day after the Baseline Visit. Specifics 
about which days and times during those days can be used for play will be free to 
vary among the participants based on their schedules. Time of play will be 
captured. Therapeutic play should continue up until the day prior to the End of 
Treatment visit (Visit 2.). 
Prior to initiating play, the subject should block out 25 minutes of uninterrupted 
time in a quite location where he or she can focus on playing their therapy. It's 
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very important that only the study subject plays the therapy. 
should anyone else be allowed to play the therapy. 
1.02 
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At no other time 
Also, it's important to make sure the iPad is connected to the participants home 
Wi-Fi. If home Wi-Fi is not available the study staff and parents need to establish 
a plan where the iPad will be connected to remote Wi-Fi on a periodic basis 
during subject play (Note: The remote Wi-Fi location should not require webpage 
authentication). The iPad will cache all data locally but without Wi-Fi access the 
study sites will not receive accurate compliance reports 
To initiate play, the subject taps on the game therapy icon displayed on the 
screen and follows the in-program instructions. 
Also, separate hard-copy 
instructions will be sent home with the parent. The instructions are specific to 
EVO Multitasking or EVO Words therapies, so the un-blinded clinical coordinator 
will need to provide these. 
For any calendar day the therapy will automatically lock after approximately 25 
minutes of play and no further play will be allowed until the next calendar day. 
For EVO Multitasking this lockout is accomplished after the subject completes 5 
"sessions" of 4 to 5 minutes each. For EVO Words, the therapy stops after 25 
minutes. 
5.2 Potential Benefits/Risks of Study Device 
Based on preliminary data obtained in several studies, including a Proof-of-
Concept trial in children with ADHD, the potential benefits of the EVO 
Multitasking game-based therapy for this population are to increase attentional 
functioning. Given the central role of attention in the pathophysiology of ADHD, 
this benefit is substantial. 
To date, there have been no adverse events reported across several early 
studies with the device. The risk/benefit ratio for use is favorable. 
Use of the EVO Words therapy has not been evaluated systematically. However, 
no adverse events are expected with the amount of play required in the present 
study. Moreover, given the nature of the EVO Words therapy, expected benefit 
for the primary outcome measure and secondary measures is expected to be 
minimal. 
The risks to a participant participating 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 by some of the tasks. The participant could become fatigued by the 
computer tests or therapeutic play. 
If the participant becomes frustrated or 
fatigued, they may stop at any time. There is a risk that the participant may 
access unintended features (e.g. Music, Contacts, Reminders, Notes, or 
Calendar) during the course of their participation in the at-home portion of this 
study. In this instance, the participant may enter personal information onto the 
device. To circumvent associated risk, all data entered by the participant onto the 
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device will be erased before reusing the device. There are no other risks to 
taking part in this study of which we are aware. 
The participant will not receive any direct benefit from participating in this study. 
No guarantee can be made concerning the study outcome, because results from 
a clinical research study cannot be predicted. 
5.3 Procedures for Monitoring Compliance and Replacing Participants 
Both EVO Multitask and EVO Words automatically capture gameplay compliance 
and upload these data directly to a central server when connected to Wi-Fi. The 
server will automatically push daily compliance emails to the clinical sites (the 
format of which is described in a separate document). Based on these emails, 
un-blinded study staff can then reach out to the parents or participants (via the 
preferred contact method captured in the demographic collection) to trouble 
shoot technical problems and/or encourage more play. The rules for compliance 
outreach follow: 
1) Participants that fail to play any EVO Multitask or EVO Words sessions 
over two or more days will be contacted to trouble shoot potential Wi-Fi 
connection problems (These participants will be highlighted in yellow in 
the daily compliance email 
2) Participants fail to play at least 5 sessions of EVO Multitask or 25 minutes 
of EVO Words over 3 or more days will be contacted and reminded to play 
more (These participants will be highlighted in yellow in the daily compliance 
email) 
3) Participants that fail to play any EVO Multitask or EVO Words sessions 
over 7 days will be replaced (These participants will be highlighted in red in 
the daily compliance report). These participants should NOT be told they are 
being replaced and should be encouraged to keep playing (as with other 
participants) and reminded to return to the clinic for their exit visit at the end 
of the study. 
4) Participants that fail to play at least 12 sessions of EVO Multitask or 60 
minutes of EVO Words over 14 days will be replaced (These participants will 
be highlighted in red in the daily compliance report). These participants 
should NOT be told they are being replaced and should be encouraged to 
keep playing (as with other participants) and reminded to return to the clinic 
for their exit visit at the end of the study. 
Additionally, parents will receive a weekly and automatically generated progress 
email report directly from the Sponsor (Akili), unless they have opted-out at the 
time of informed consent. 
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Note: In the event a subject does not return to the clinic for their final exit visit or 
does not complete their assessments during the exit visit, this subject will be 
replaced. 
5.4 Discontinua tion of Study Device 
Participants may withdraw at any time during the study without prejudice or be 
discontinued from study treatment at the discretion of the investigator if medically 
necessary or if any untoward effects occur. In addition, a subject may be 
withdrawn by the investigator or DCRI if the subject is noncompliant with their 
assigned treatment (as described above) or otherwise violates the study plan, or 
for administrative and/or other safety reason. In the case where a subject 
withdraws from the study, the subject will be replaced. 
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. When a subject discontinues or is withdrawn 
from treatment before study completion, all applicable activities scheduled for the 
final study visit should be performed at the time of discontinuation. 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 7.0 (Adverse Events). 
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6 CONCOMITANT MEDICATIONS 
Central nervous system stimulants will be discontinued at the beginning of the 
washout phase and not allowed for the duration of the trial. 
6.1 Allowed Medications 
Non-sedating antihistamines 
Analgesics including acetaminophen and ibuprofen 
Antibiotics required for the treatment of minor illnesses 
Vitamins 
6.2 Prohibited Medications 
Prohibited medications 30 days prior to screening (for this purpose, defined as 
the day of informed consent) and through the duration of the trial include: 
SSRls (e.g., fluoxetine , paroxetine) 
MAOls (monoamine oxidase inhibitors) 
Mood stabilizers (e.g., lithium, valproate , quetiapine) 
Antipsychotics (e.g., risperidone, olanzapine) 
Anticonvulsants (e.g., phenobarbital , phenytoin, primidone) 
Anticoagulants 
Dextromethorphan 
Halogenated anesthetics 
Tricyclic antidepressants 
Atomoxetine 
Guanfacine 
Clonidine 
Phenylbutazone 
Sedating antihistamines 
Decongestants with stimulant properties 
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7.0 ADVERSE DEVICE EFFECT REPORTING AND FOLLOW-UP 
7.1 
Definitions 
Adverse Device Effect (ADE) 
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 use error or intentional misuse. 
Unanticipated Adverse Device Effects (UADEs) 
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 either A or B 
as stated below: 
A. Events meeting ALL of the following criteria: 
• 
Not included in the list of Anticipated Events (refer to I protocol 
section 7 .3) 
• 
Possibly, probably, or definitely related to the investigational 
device per the site principal investigator 
Serious (meets any of the following criteria): 
o Is life-threatening illness or injury 
o Results in permanent impairment of a body structure 
or a body structure 
o Necessitates medical or surgical intervention to 
prevent permanent impairment of a body function or a 
body structure 
o Led to fetal distress, fetal death or a congenital 
abnormality or birth defect 
o Led to death 
(Permanent means irreversible impairment or damage to a body 
structure or function, excluding trivial impairment or damage). 
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B. Any other unanticipated serious problem associated with the investigational 
device that relates to the rights, safety, or welfare of participants. 
7 .2 
Assessment 
7.2.1Time Frame 
An ADE observed from the time of randomization through the final 
study visit (day 28) will be collected in clinical database eCOS 
7.2.2 Causality Rating 
The causal relationship of an adverse event to either study game 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). 
7.2.3 Severity of Adverse Device Effects 
The severity of an ADE will be rated as follows: 
• 
Mild: Awareness of sign, symptom , or event, but easily tolerated. 
• 
Moderate : Discomfort enough to cause interference with usual activity 
and may warrant intervention. 
• 
Severe: Incapacitating with inability to do usual activities or 
significantly affects clinical status and warrants intervention. 
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7.3 Previously Noted Adverse Device Effects 
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The expectedness of an ADE shall be documented in the informed consent 
(ICF). Any ADE that is not identified in nature, severity, or is not listed below is 
considered unanticipated. 
Adverse Device Effects EXPECTED FOR THIS DEVICE: 
1. Dizziness 
2. Nausea 
3. Headache 
4. Increased and unusual levels of frustration during game play 
7 .4 
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 EDC as it becomes available. 
7.4.1 Adverse device effect 
The investigator must report, via eCOS, all Adverse device effects, 
anticipated 
or 
unanticipated, 
occurring 
from 
the 
time 
of 
randomization through the final study visit (day 28) within 24 hours 
of knowledge of the event. If the eCRF system is temporarily 
unavailable, the 
event, including 
investigator-determined causality 
assessment, should be reported to DCRI via a paper back-up ADE form. 
Upon return of the availability of the eCOS system, the ADE information 
must be entered into the eCRF. 
The investigator must report, via eCOS, when important follow-up 
information (final diagnosis, outcome, results of specific investigations, 
etc.) becomes available after submission of the initial Suspected Adverse 
Reaction 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 eCOS). All 
adverse device effects will be followed through resolution. 
DCRI Safety Surveillance will report all adverse device effects to specified 
trial personnel (sponsor, principal investigator [Pl] and project leader) 
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within 1 to 2 business days of receipt. 
7.4.2 Regulatory Reporting of Unanticipated Adverse Device Effects 
If an investigator reports an UADE to the sponsor (via the EDC), the 
sponsor shall immediately conduct an evaluation of the UADE and will 
make a determination as to whether it meets the "unanticipated" criteria 
(i.e., are not listed in section 7.3 of the protocol) and whether it meets the 
criteria for reporting to regulatory authorities (e.g. FDA, IRBs). 
Any UADE(s) that the sponsor determines is/are reportable will be 
submitted to the FDA, all reviewing IRBs, and all participating investigators 
within 10 working days of when the sponsor makes that determination. 
If the sponsor determines that an UADE presents an unreasonable risk to 
participants, all investigations or parts of investigations presenting that risk 
shall be terminated 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. 
All Regulatory Reporting to the FDA will be done by DCRI Regulatory. 
7.5. Institutional Review Boards 
All sites will submit the study Adverse Device Effects, Unexpected Adverse 
Device Effects, Adverse Events and Serious Adverse Events to their local/central 
Institutional Review Board (IRB) according to their local IRB polices and 
procedure. 
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8.0 STATISTICAL ANALYSES 
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This section will provide an overview of the statistical , descriptive, and qualitative 
analyses for this study. Specific details of the analyses will be described in a 
separate statistical analysis plan (SAP) 
The main objective of this study is as follows: 
• 
To evaluate the effects of EVO Multitask game-based digital therapy 
versus EVO Words game-based digital therapy on attentional functioning 
(measured by the TOVA API score change) and ADHD symptoms 
(measured by gold-standard qualitative rating scales). 
This study has 1 primary and 3 secondary objectives . Success on the Primary 
(P1) and the first Secondary Objective (S1) (Change in ADHD symptoms) will 
provide confirmatory support for the full claim above. If the primary is successful , 
but the ADHD symptom secondary objective fails to meet statistical significance, 
the modified claim below will still be supported: 
• 
To evaluate the effects of EVO Multitask game-based digital therapy 
versus EVO Words game-based digital therapy on attentional functioning 
(measured by the TOVA API score change). 
Below is a list of primary, secondary , exploratory , safety, and descriptive 
objectives. 
Missing data and site poolability are addressed as descriptive 
objectives. Details on measures collected are provided in the SAP. 
8.1 Primary Objective (P1) - Attention 
P1-Objective) To evaluate the effects of EVO Multitask play versus EVO 
Words play on attentional functioning (measured by the API composite score 
from the TOVA 8). 
P1-Outcome Measure(s)) Change from baseline to day 28 on TOVA API 
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The TOVA is a clinically-relevant and validated continuous performance test 
(CPT) that informs attentional performance in ADHD populations. The API score 
is a composite variable that summarizes the overall result of the TOVA and is 
composed of age/gender adjusted (z-scores) of reaction time variability, mean 
reaction time, and sensitivity to the target stimuli (d') 
8.2 Secondary Objectives 
8.2.1 Major Secondary Objective I (51) - ADHD Symptoms 
S1-0b jective) To evaluate the effects of EVO Multitask play versus EVO 
Words play on ADHD symptoms using clinically relevant qualitative rating 
scales of ADHD symptoms , executive function , and global function. 
S1-0u tcome Measures(s)) 
• 
ADHD-RS Total (Change from baseline to day 28) 
• 
ADHD-RS Inattentive Sub-scale (Change from baseline to day 28) 
• 
ADHD-RS Hyperactivity Sub-scale (Change from baseline to day 
28) 
• 
BRIEF Working Memory Percentile (Change from baseline to day 
28) 
• 
BRIEF Inhibit Percentile (Change from baseline to day 28) 
• 
Impairment Rating Scale (IRS) (Change from baseline to day 28) 
• 
Clinician Global Improvement (CGI) (at day 28) 
8.2.2 Minor Secondary Objective II (S2) - Objective Working Memory 
S2-0bjective) To evaluate the effects of EVO Multitask versus EVO Words 
play on objective working memory function as measured by CANTAB's 
Spatial Working Memory (SWM) computerized test. 
S2-0utcome Measure(s)) 8 CANTAB SWM outcome measures (Change 
from baseline to day 28) 
• 
Mean time to first response (4 boxes) 
• 
Mean time to last response (4 boxes) 
• 
Mean token-search preparation time (4 boxes) 
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• 
S.D. time to first response (4 boxes) 
• 
S.D. time to last response (4 boxes) 
• 
S.D. token-search preparation time (4 boxes) 
• 
Strategy ( 4 to 8 boxes) 
• 
Total Errors 
8.2.3 Minor Secondary Objective Ill (S3) - Objective Inhibition 
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S3-Objective) To evaluate the effects of EVO Multitask versus EVO Words 
play on inhibitory function as measured by TOVA Commission Error 
Standard Score (non-composite score) during the frequent response 
portion of the TOVA (COMSSH2) . 
S3-Outcome Measure(s))-
TOVA COMMSSH2 
8.3 Exploratory Objectives 
This section will list the planned exploratory analyses . Full details are provided in 
the SAP. 
8.3.1 Exploratory Objective I (E1) - Responders 
E1-Objective) To evaluate the percentage of responders for select 
outcome measures in both the EVO: Multi and EVO: Words groups. 
E1-Outcome Measure(s)) The following outcomes will be examined ; 
• 
TOVAAPI 
• 
ADHD-RS Total 
• 
CGI 
• 
IRS 
Responder cut-off values and details of this analysis will be described in 
the SAP. 
8.3.2 Exploratory Objective II (E2) - Additional TOVA Endpoints 
E2-Objective) To evaluate the effects of EVO Multitask play versus EVO 
Words play on additional TOVA endpoints 
not analyzed in other 
objectives . 
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E2-Measures) Multiple TOVA outcomes 
28). See SAP for a list of measures. 
(Change from baseline to day 
8.4 Safety Analysis 
Treatment related adverse events for both the EVO Multitask and EVO Words 
interventions will be presented. Any adverse events occurring during any phase 
of the study judged by clinical sites' Primary Investigator (Pl) to be related to 
either intervention will be recorded and presented in a table listing. The Safety 
population (see section 8.6.2 for analysis population details) will be used for this 
analysis that will include randomized participants that began the at-home training 
phase for either intervention. The severity of each event will be evaluated by the 
Pl and presented with the recorded events. If there are frequently occurring 
treatment related adverse events, a frequency table will be included, to rank 
events from most frequent to most rare. Subjects will be included in the actual 
treatment group received. 
8.5 Descriptive Analyses 
The following additional descriptive analyses will be conducted. Details are 
provided in the SAP. 
• 
01 : Gameplay Surveys 
• 
02 : Compliance 
• 
03 : Age and Gender Sensitivity Analysis 
• 
04 : Site Poolability Sensitivity Analysis 
• 
05 : Missing Data Sensitivity Analysis 
• 
06 : Baseline TOVA API sensitivity analysis 
• 
07 : Baseline Parent Expectancy Sensitivity Analysis 
8.6 General Statistical Methods 
This section will present the formal hypotheses, analysis populations, multiplicity 
adjustment consideration, and methods for handling missing data. In addition, 
details about the planned interim analysis and statistical power are presented. 
8.6.1 Hypothesis Tests and Multiplicity Adjustments 
The aim of all primary and secondary objectives in this study are to 
demonstrate a statistical difference on outcome measure mean change 
scores between the EVO Multitask group and the EVO Words group. Change 
scores are defined as the score obtained on the pre-training assessment 
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subtracted from the post-training assessment (Post -
Pre). Change score 
group means will be compared using a 2-tailed between participants T-Test 
with a base alpha criterion of 0.05 to meet statistical significance . Note: The 
assumpt ions for a T-Test will be checked and if the assumptions do not hold 
true , then other appropriate methods will be used as described in the SAP. 
Below are general formulations 
of the null and alternative statistical 
hypotheses , 
• 
Ho: µE VOMULTI : 
µ EVOWOROS (1) 
• 
H( µE VOMULTI # µ EVOWORDS (2) 
where Ho is the null hypothesis , H1 is the alternative hypothes is, µ EvoMuLT1 is 
the mean change score for the EVO Multitask group, and µ EvowoRos 
is the 
mean of the change score for the EVO Words group . The Primary Objective 
(P1) is a special case of this hypothesis test that will use weighted scores to 
control for Type-I error increases due to a sample size re-estimation and 
potential sample size increase at the interim analysis. 
The calculation of 
weighed scores will use the Chu-Hung-Wang method (Chang, 2014; Chu, 
Hung, & Wang , 1999). 
Multiplicity will be controlled across the Major Objectives of this study (P1 and 
S1). See the SAP for details on multiplicity adjustments 
8.6.2 Analysis Populations 
Three populations are defined for this study : A per-protoco l (PP), intention-to -
treat (ITT), and safety population . The ITT and PP populations will be used 
for all efficacy analyses. The Safety popu lation will be used for the safety 
analysis. The success of the primary and secondary objectives will be based 
on an assessment of the results from the ITT population . Additional analysis 
of the PP population is supportive . 
The primary efficacy endpoint must 
achieve significance in the ITT to preserved type I error for the secondary 
endpoints . Details about inclusion into each population are presented below : 
• 
Per-Protocol (Treatment Complaint ): This population is defined as any 
participant that began the at-home phase , completed both the pre and 
post assessment , and met a minimum compliance level of 50%. 
Additionally the following participants are excluded from this 
population : 
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o Participants where the subjective clinical assessments (ADHD-
RS, CGI, and IRS) were not made by the same study staff 
member pre and post 
o Participants where it was reported that the blinding was broken 
o Participants that received incorrect intervention after 
randomization 
o Participants who used prohibited/exclusionary medication or 
other treatments for ADHD during the course of the trial 
• 
Intention-to-Treat (ITT): This population is defined as any randomized 
participant that received a device for at home training. In the case 
participants received the incorrect intervention after randomization, no 
corrections to group assignment will be made. 
• 
Safety: This population is defined as any randomized participant that 
received a device for at home training. The primary safety analyses 
will include participants regardless of if they completed the post-
treatment assessment and will be analyzed in the group whose 
treatment they actually received. 
8.6.3 Interim Analyses 
An interim analysis will be conducted on the primary outcome, TOVA 8 API, 
to determine if the minimum sample size of 300 patients is sufficient to detect 
a statistical difference between EVO Multitask and EVO Words. 
The 
population for this analysis will follow the same guidelines used for inclusion 
into the ITT population (See section 8.6.2). 
The specific results of the interim analysis will remain blinded and will not be 
used to declare success of the primary objective at the interim; Un-blinded 
staff at the DCRI will conduct this analysis for the purpose of finalizing the 
sample size only. To maintain blinding for all other study personnel and 
affiliates, the results of this analysis will only indicate the sample size 
necessary to sustain the power of the study to detect an effect size of 0.4. 
Enrollment in the study will continue until the at least a minimum of 300 
patients have been enrolled and the study has achieve the number of 
enrolled patients necessary to sustain the power of the study. The study will 
not exceed 1,000 enrolled patients. Additional details on the interim analysis 
will be presented in the SAP. 
8.6.4 Power and Sample Size 
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To determine an appropriate study sample size to detect a statistical 
difference between change scores of the EVO Multitask group vs. the EVO 
Words group, a preliminary power analysis was conducted. The results 
indicated that 150 participants per group is sufficient to detect an effect size of 
0.40 at a power > 90% on a between participants T-test with an alpha 
criterion of 0.05. 
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9. DAT A AND SAFETY MONITORING 
9.1 Endpoint Determination 
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API scores from the TOVA 8 will be derived directly from the computers 
used to administer the task and these scores will be entered into the 
database for analysis of primary outcome 
9.2 Safety Monitoring 
Safety/tolerability will be assessed primarily at the Post-Treatment Visit 
(Visit 3), as well as during the 4-week game play component as 
necessary. 
9.3 Data Management to Maintain Blinding 
As noted above (Section 4.7), instructions will be given to participants, their 
parents and study staff to minimize the possibility that information that may 
potentially unblind treatment assignment (e.g., parent or participant description of 
their assigned game content) is limited. 
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10 DATA MONITORING AND QUALI TY CONTROL 
10.1 Required Data 
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The full study dataset will be collected for participants who enter the treatment 
phase of the study. Limited data (i.e., demographics, adverse events, selection 
criteria, and reason for discontinuation) will be collected for participants who 
discontinue before the treatment phase. 
All required data for this study will be entered into the electronic case report form 
(eCRF). 
10.2 Subject and Clinical Data 
The collection site will provide the following 
This study will use Web-based e-CRFs developed through a validated, electronic 
reporting-electronic-signatures-compliant 
platform 
(21 
Code 
of 
Federal 
Regulations Part 11 ). Before initiation of the trial, each site will be contacted as to 
computer availability, hardware specifications, and Internet connectivity, to 
evaluate the capacity of the site to use this type of data collection system. The 
investigator's site staff who will be entering data will receive training on the 
system, after which each person will be issued a unique user identification (ID) 
and password. 
For security reasons, and in compliance with regulatory guidelines, it is 
imperative that only the persons who own the user IDs and passwords access 
the system using their own unique access codes. Access codes are 
nontransferable. Site personnel who have not undergone training may not use 
the system and will not be issued user ID and password until appropriate training 
is completed. 
During monitoring visits, the site will make their computer and/or high-speed 
Internet access available to the clinical research associate. At the conclusion of 
the study, each enrolling site will be provided with a compact disc containing PDF 
files of both the individual subject's data and the audit trail (changes made to the 
database). This will be maintained at the site according to the requirements for 
records retention. 
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11 STUDY RESPONSIBILITIES 
11.1 Study Data Reporting and Processing 
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Each page of the electronic case report form (eCRF) will be reviewed by site Pl 
at the site. The site Pl is required to sign the eCRF on the appropriate pages to 
verify that he or she has reviewed the recorded data. This review and sign-off 
may be delegated to a qualified clinician appointed as a sub investigator by the 
site Pl. The transfer of duties to a sub investigator will be recorded on the 
delegation list (kept on file at the site). The investigator must ensure that all site 
staff involved in the conduct of the trial are familiar with the protocol and all 
study-specific procedures, and that they have appropriate knowledge of the study 
agents. 
11.2 Training 
The training of appropriate clinical site personnel across study procedures will be 
the responsibility of Akili Interactive Labs, Inc. and/or their representative(s) 
(EVO Multitask and EVO Words, CANTAB, TOVA, compliance monitoring) and 
DCRI (Protocol procedures, MINI-KID , ADHD-RS, eCRF/data entry, AE 
reporting, general test administration). The site Pl is responsible for ensuring that 
his or her staff conduct the study according to the protocol. To ensure proper 
administration of study interventions, uniform data collection, and protocol 
compliance, Akili Interactive Labs, Inc. and their representatives and DCRI will 
present a formal training session to study site personnel, to include instructions 
for study procedures, the investigational plan, instructions on data collection, 
methods schedules for follow-up with the study site coordinators, and regulatory 
requirements. Detailed feedback regarding completion of forms will be provided 
by Akili Interactive Labs, Inc. and their representatives and DCRI in the course of 
regular site monitoring. 
11.3 Monitoring the lnvestigational Sites 
As part of a concerted effort to follow the study in a detailed and orderly manner 
in accordance with established principles of GCP and applicable regulations, a 
study monitor will visit the study sites regularly and will maintain frequent 
telephone and written communication. Additional information regarding site 
management and monitoring can be found in the Clinical Monitoring Plan (CMP). 
During monitoring visits, the monitor will review informed consent, and HIPAA 
authorization, all inclusion/exclusion criteria, all events meeting criteria for 
expedited event reporting, as well as safety and efficacy endpoints. Additional 
review will be performed on a site-by-site basis, as warranted by the findings of 
previous monitoring visits. Key variables (demographics, inclusion/exclusion 
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criteria, and safety) on the eCRFs will be compared with each subject's source 
documents. Any discrepancies will be noted and resolved. 
11.4 Study Documentation 
Study documentation includes all electronic case report forms, source 
documents, monitoring logs and appointment schedules, sponsor-investigator 
correspondence, and regulatory documents 
(e.g., signed protocol and 
amendments, IRB or EC correspondence and approval, approved and signed 
subject consent forms, Statement of Investigator form, clinical supplies receipts 
and distribution records). 
The site Pl is responsible for ensuring that complete and accurate is prepare and 
maintain in compliance with GCP standards and applicable federal, state, and 
local laws, rules and regulations; and, for each subject participating in the study, 
promptly complete all eCRFs and such other reports as required by this protocol 
following completion or termination of the clinical study or as otherwise required 
pursuant to any agreement with the sponsor or their designated representative. 
By signing the protocol, the site Pl acknowledges that, within legal and regulatory 
restrictions and institutional and ethical considerations, study documentation will 
be promptly and fully disclosed to the sponsor or their designated representative 
by the investigator upon request and also shall be made available at the 
investigator's site upon request for inspection, copying, review, and audit at 
reasonable times by representatives of the Sponsor and the sponsor or their 
designated representative, or responsible government agencies as required by 
law. 
The site Pl agrees to promptly ensure that any reasonable steps that are 
requested by Sponsor or the sponsor or their designated representative as a 
result of an audit to cure deficiencies in the study documentation and eCRFs are 
taken. 
11.5 Protocol Deviations 
A protocol deviation is defined as an event where the investigator or site 
personnel did not conduct the study according to the investigational plan or the 
Investigator Agreement. 
Investigators are required to obtain approval from the sponsor or their designated 
representative 
medical 
monitor 
before 
initiating 
deviations 
from 
the 
investigational plan or protocol, except where necessary to protect the life or 
physical well-being of a subject in an emergency. Such approval will be 
documented in writing and maintained in study files. Unless the Sponsor has 
consented to any such deviations in writing, Sponsor will not assume any 
resulting responsibility or liability. Preapproval is generally not expected in 
situations where unforeseen circumstances are beyond the investigator's control, 
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(e.g., subject did not attend scheduled follow-up visit,); however, the event is still 
considered a deviation. 
The I RB will be informed of all protocol changes by the sponsor or deviations that 
occur at the investigative site in accordance with applicable regulations and the 
IRB/EC's established procedures. No deviations from the protocol of any type will 
be made without complying with all the IRB/EC's established procedures. 
11.6 Study Supply Accountability 
The investigator will maintain records of the receipt and disposition of all 
investigational devices (i.e., tablets), including any reported instances of 
unintended usage. When the enrollment is complete, the investigator will be 
notified by the sponsor or their designated representative, and in a timely 
manner, will return all study devices as directed by the Sponsor. 
11. 7 Data Transmittal and Record Retention 
Required data will be entered in the eCRF as soon as possible after the subject 
visit or the availability of test results, but no later than 3 business days after the 
completed visit. 
Study sites will transcribe subject source data into eCRFs using a computerized 
electronic data capture (EDC) system. The EDC system is compliant with all 
relevant aspects of GCP. Edit checks, electronic queries, and audit trails are built 
into the system to ensure accurate and complete data collection. Data will be 
transmitted via the Internet from investigational sites to a central site, utilizing 
state-of-the-art encryption mechanisms to ensure security and confidentiality. 
The eCRF will be transmitted to a secure central database (host site) as forms 
are completed or updated. Protocol-specified source documents will be retrieved 
as necessary. Originals of all study-related documentation will be retained at the 
site. 
The site Pl will maintain the records of device/tablet disposition, final eCRFs, 
worksheets, and all other study-specific documentation (e.g., study file notebooks 
or source documentation) until notified by the sponsor that records may be 
destroyed. To avoid error, the investigator will contact the sponsor or their 
designated representative before the destruction of any records pertaining to the 
study to ensure they no longer need to be retained. In addition, the sponsor will 
be contacted if the site Pl plans to leave the institution so that arrangements can 
be made for the transfer of records. 
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11.8 Study Closeout 
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Upon completion of the study (defined as all participants have completed all 
follow-up visits, all eCRFs are complete, and all queries have been resolved), the 
sponsor or their designated representative will notify the site of closeout, and a 
study closeout visit will be performed. All devices will be collected and returned to 
the sponsor or their designated representative. The sponsor or their designated 
representative monitor will ensure that the site Pl's regulatory files are up-to-date 
and complete and that any outstanding issues from previous visits have been 
resolved. Other issues to be reviewed at the closeout visit include discussing 
retention of study files, possibility of site audits, publication policy, and notifying 
the IRB of study closure. 
11.9 Audit/Inspections 
The sponsor or their designated representative quality assurance personnel may 
conduct audits at the study sites. Audits will include, but not be limited to, audit 
trail of data handling and processes, standard operating procedures, device 
supply, presence of required documents, the informed consent process, and 
comparison of eCRFs with source documents. The site Pl agrees to 
accommodate and participate in audits conducted at a reasonable time and in a 
reasonable manner, as needed. 
The FDA may also inspect the site during or after the study. The site Pl should 
contact the sponsor immediately if this occurs and must fully cooperate with 
governmental (e.g., FDA) inspections conducted at a reasonable time and in a 
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12. REFERENCES 
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Biederman, J, et al. Evidence of a pharmacological dissociation between the 
robust effects of methylphenidate on ADHD symptoms and working memory. 
Journal of Brain Science 2015; 1 (2) 43-53 
Klinberg T. Training and Plasticity of Working Memory. Trends in Cognitive 
Sciences. 2010; 14(2) 317-314 
Cortese, S, et al. Cognitive Training for Attention DeficiUHyperactivity Disorder; 
Meta-Analysis of Clinical and Psychological Outcomes from Randomized 
Controlled Trials. Journal of American Academy of Child and Adolescent 
Psychiatry 2015; 54(3) 164-174. 
Anguera, J.A., et al. Video Game Training Enhances Cognitive Control in Older 
Adults. Nature 2013; 501, 97-101. 
Blackwelder WC. "Proving the null hypothesis" in clinical trials. Control Clin 
Trials. 1982;3:345-53 
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