Software Treatment for Actively Reducing Severity of ADHD as Adjunctive Treatment to Stimulant

Software Treatment for Actively Reducing Severity of ADHD as Adjunctive Treatment to Stimulant (STARS-ADHD Adjunctive)

The purpose of this study is to determine the effects of combining AKL-T01 (with AKL-X01 symptom tracking) as adjunctive treatment to stimulant medication, and to understand the effects of AKL-T01 treatment (with AKL-X01 symptom tracking) in participants not recently on medication.

The study aims to enroll (203) participants, with a confirmed diagnoses of ADHD, at approximately 15 sites and will be divided between 2 cohorts; 130 participants will be enrolled in Cohort 1, and 73 participants will be enrolled in Cohort 2.

Cohort 1 will have been stable (adherence to a prescribed medication schedule) on a stimulant medication, but are inadequately managed by the stimulant (in the opinion of the investigator). The stimulant is managed by their own physician for at least 30 days before baseline. This is the Stimulant cohort.

Cohort 2 will have been stable without any stimulant medication for at least 30 days before the baseline. This is the Non-Stimulant cohort.

For both cohorts, at least 7 and up to 30 days before baseline, participants' caretakers will begin using AKL-X01 (Fengo) to track their participants' symptoms and behaviors.

During Treatment Phase 1 (Days 1 through 28) participants in Cohort 1 (Stimulant) will continue to receive their current stimulant plus the addition of AKL-T01. Participants in Cohort 2 (Non-Stimulant) will just receive AKL-T01. For both cohorts, during this time the caretakers will monitor their child's symptoms daily with AKL-X01.

During the 1-Month Break (Days 29 through 56) between AKL-T01 treatment phases, participants in Cohort 1 will continue to receive their current stimulant. In both cohorts, AKL-T01 will be suspended during this time. For both cohorts, during this time caretakers will continue to monitor their child's symptoms daily with AKL-X01.

During Treatment Phase 2 (Days 57 through 84), participants in Cohort 1 (stimulant) will continue to receive their current stimulant plus the addition of AKL-T01. Participants in Cohort 2 will just receive AKL-T01. For both cohorts, during this time the caretakers will monitor their child's symptoms daily with AKL-X01.

AKL-T01, or EVO Multi, is a digital intervention that requires the subject to navigate a character through a game-like space, while collecting objects, in a fixed period of time.

AKL-T01: Videogame-like digital therapy

Inclusion Criteria:

1. Male or female, ages 8 years 0 months to 14 years 9 months (inclusive), at the time of parental informed consent.

2. Confirmed ADHD diagnosis (primarily inattentive or combined subtype), at Screening based on DSM-V criteria and established via the MINI-KID administered by a trained clinician.

   Note: Co-morbid diagnoses on the MINI-KID are acceptable provided that ADHD is the primary diagnosis and the co-morbid diagnoses will not confound study data (per the Investigator's judgment).

3. Currently experiencing sub-optimal treatment of ADHD, based upon results of Clinical Global Impression-Severity score.

4. Impairment Rating Scale (Parent Report) score of ≥ 3 at Screening.

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

6. Estimated IQ score > 80 as assessed by the Kaufmann Brief Intelligence Test, Second Edition (KBIT-II).

7. Ability to comply with all testing, requirements, study procedures, and availability for the duration of the study.

8. Provision of signed and dated parental informed consent form and assent form.

9. Participant's parent and/or caregiver has access any of the following Apple™ or Android™ smart phone and/or mobile devices (for accessing AKL-X01 application): Apple iPhone 6, 6+, 7, 8, 10; Android Samsung Galaxy S7, S7 Edge, S8, S8+, S9, S9+; Android Samsung Note 8; Android LG G6, G7, V30, K20. Apple mobile devices must be running iOS 11.2+. Android mobile devices must be running Nougat or Marshmallow.

10. For Cohort 1 (stimulant), participant must be stable** on stimulant medication, at an approved FDA dose , for ≥ 30 days prior to enrollment (may also be one stimulant plus a booster, provided that the dose is stable and does not change throughout the course of the trial).

    **Note: Medication stability is defined as:

    • Moderate response on stimulant, but still room for improvement
    • Dose unchanged within past 30 days, but other doses have been tried previously without improvement
    • Currently taking stimulant, but parent and/or caregiver wishes not to increase dosage for any reason
    • Taking consistent stimulant dose on weekdays, but not on weekends

11. For Cohort 2 (non-stimulant), participant must be stable off stimulant medication for ≥ 30 days prior to enrollment.

Exclusion Criteria:

1. 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:

   1. post-traumatic stress disorder
   2. psychosis
   3. bipolar illness
   4. pervasive developmental disorder
   5. severe obsessive compulsive disorder
   6. severe depressive
   7. severe anxiety disorder
   8. conduct disorder
   9. other symptomatic manifestations that in the opinion of the Investigator may confound study data/assessments.

   Participants with clinical history of learning disorders will be allowed to participate, provided the disorder does not impact their ability to participate in the trial based on PI judgment.

2. Participants who are currently treated with a non-stimulant medication for ADHD (i.e., atomoxetine, clonidine, guanfacine).

3. Participants diagnosed with ADHD Hyperactive-Impulsive subtype, based upon score on the MINI-KID interview.

4. Participants showing no room for improvement, or those refractory to non-intensive ADHD treatment.

5. Initiation within the last 4 weeks from the time of consent of behavioral therapy. Participants who have been in behavior therapy consistently for more than 4 weeks may participate provided their therapy frequency and intensity 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.

6. 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 Screening.

7. Motor condition (e.g., physical deformity of the hands/arms; prostheses) that prevents playing the digital treatment as reported by the parent or observed by the investigator.

8. Recent history (within the past 6 months) of suspected substance abuse or dependence

9. History of seizures (exclusive of febrile seizures), or significant motor or vocal tics, including but not limited to Tourette's Disorder)

10. Has participated in a clinical trial within 90 days prior to Screening.

11. Diagnosis of or parent-reported color blindness (Confirmed in-clinic via ICBT)

12. Uncorrected visual acuity (confirmed in-clinic, via ability of participant to play the game, at Screening)

13. Regular use of psychoactive drugs (non-stimulant) that in the opinion of the Investigator may confound study data/assessments.

14. Any other medical, behavioral, or developmental condition that in the opinion of the investigator may confound study data/assessments.

15. Has a sibling also enrolled/currently participating in the same study. Siblings may participate in the study sequentially, but not at the same time.

16. Has previously been randomized in a study of Akili's videogame-like digital treatment.