Software Treatments for Actively Reducing Severity of Cognitive Deficits in MDD (STARS-MDD)

The study will be a randomized, parallel group, controlled trial of two videogame-like
(iPad-based) digital therapies. The study will consist of 3 primary phases: Pre-screening,
Baseline, and Treatment. During the Pre-screening Phase (Day -28 to Day 0), participants will
undergo pre-screening to evaluate eligibility for the study. Pre-screening may take place up
to 28 days before the Baseline Visit (Day 0). Pre-screening may take place either over the
phone, or in the clinic. On Day 0, the Baseline visit will occur wherein additional
eligibility criteria will be established. The Treatment Phase (Day 1 to Day 42) will involve
using the digital therapy at home for each participant followed by an In-Clinic assessment on
Day 42 to assess key outcomes. During the Treatment Phase participants will be instructed to
play their videogame-like intervention for approximately 25 minutes per day for 5 days per
week. Compliance with treatment/use requirements will be monitored remotely during this
phase.

Inclusion Criteria:

- Primary diagnosis of recurrent Major Depressive Disorder (MDD) according to Diagnostic
and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) as confirmed by MINI
Version 7.0.2.

- Pre-Screening (Day≤-28) Remote or In-Clinic

- Screening/Day 0 (in-clinic) including:

- HAM-D-17 score

- BAC Symbol Coding T-test score

- On stable antidepressant medication for ≥8 weeks prior to screening/baseline, with
stable dose for ≥4 weeks prior to baseline/baseline, with or without stable adjunct
psychotherapy (excluding DBT or CBT) for ≥12 weeks.

- Access to and self-report of ability to connect wireless devices to a functional
wireless network

- Ability to follow written and verbal instructions (English) as assessed by the PI
and/or study coordinator

- Normal color vision as tested by Ishihara Color Blindness Test

- Able to comply with all testing and requirements

Exclusion Criteria:

- Current controlled (requiring a restricted medication) or uncontrolled, comorbid
psychiatric diagnosis 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 anxiety disorder,
conduct disorder, ADHD or other symptomatic manifestations that in the opinion of the
Investigator may confound study data/assessments.

- Initiation or completion of psychotherapy within the last 12 weeks prior to
screening/baseline. The participant should inform the Investigator if they intend to
change their psychotherapy during the 6 weeks of the study. Participants who have been
in psychotherapy consistently for more than 12 weeks may participate if their routine
is stable throughout the study.

- Participant is currently considered at risk for attempting suicide by the
Investigator, has made a suicide attempt within the past year, or is currently
demonstrating active suicidal ideation or self-injurious behavior, as measured by
CSSRS.

- Motor condition (e.g. physical deformity of the hands/arms) that prevents game playing
as reported by the participant or observed by the Investigator.

- Recent history (6 months prior to screening/baseline) of substance use disorder

- History of seizures (excluding febrile seizures), a tic disorder, significant tics, a
current diagnosis of Tourette's Disorder.

- Self-report of recent episodes (within the past week) of nausea, vomiting and/or
dizziness.

- Participation in a clinical trial within 3 months prior to screening.

- Color blindness as detected by Ishihara Color Blindness Test

- Regular use of psychoactive drugs other than antidepressants, including stimulants
that in the opinion of the Investigator may confound study data/assessments.

- Use of benzodiazepines >3 times per week and/or within 24 hours of baseline and exit
visit assessments prohibited.

- Use of marijuana or alcohol on the day of clinical visits before baseline or exit
assessments, no tobacco within 30 minutes of TOVA

- Any other medical condition that in the opinion of the Investigator may confound study
data/assessments.

- Previous exposure to Akili products.

- Another household member who is/has participated in this trial