Table 3.

Open-label treatment phase study timeline.

Measurement	Baselineb (Visit 9)	Month 1 (Visit 10)	Month 2d (Visit 11)	Month 3 (Visit 12)	Month 4d (Visit 13)	Month 5d (Visit 14)	Month 6 (Visit 15)	Follow-up	PRN
Visit Windows	Within 2 weeks after double-blind treatment	±14d	±14d	±14d	±14d	±14d	±14d	28d after last visit ±14d
Medical History	#	X	X	X	X	X	X	X
Clinical Interview	#	X	X	X	X	X	X
Inclusion/Exclusion criteria	X
CGI Scale: Severity & Improvement	Xc	X	X	X	X	X	X
Vital Signs		X		X			X
Physical/Neurological Exam							X		X
Dermoscopy				X			X
Microbiome/Mycobiome Sample Collection				X			X
Tanner Staging							X
Side Effects (CTCAE v5.0 + DOTES)	#	X	X	X	X	X	X	X
Columbia-Suicide Severity Rating Scale		X		X			X
Laboratory Testsa	#	X		X			X		X
Everolimus Level (Only Done After M1 If Needed)		X							X
PTEN-associated Proteins				X			X
Concomitant Treatment Log	#	X	X	X	X	X	X	X
Primary Efficacy Outcome Neurocognitive Composite	#			X			X	X
CPT-3/K-CPT-2)				X			X
SB-5/Mullen Scales of Early Learning (MSEL)							X
SB-5 Working Memory Subscale Only				X
Purdue Pegboard (PP)				X			X
Wechsler Processing Speed Index				X			X
Wide Range Assessment of Memory and Learning-2 (WRAML-2)				X			X
Peabody Picture Vocabulary Test – Fourth Edition (PPVT-4)				X			X
Expressive Vocabulary Test – Second Edition (EVT-2)				X			X
Autism Diagnostic Observation Schedule (ADOS-2)							X
Social Responsiveness Scale – Second Edition (SRS-2)				X			X
Repetitive Behavior Scale – Revised (RBS-R)				X			X
Developmental Coordination Disorder Questionnaire (DCDQ)				X			X	X
Behavior Rating Inventory of Executive Function (BRIEF)				X			X
Adult/Child Behavior Checklist				X			X	X
Sensory Profile Questionnaire - Short Form (SPQ)				x			x
Vineland Adaptive Behavior Scales (VABS-III) – caregiver report				X			X
Eye Tracking (Optional)				X			X
Resting State EEG/Auditory Evoked Potentials (Optional)				X			X

**: primary outcome mesaure only.

^aCoagulation testing will only be performed at screening, month 3 and month 6. Pregnancy testing, serum is done at screening and month 6 and urine may be used for onsite visits (if deemed clinically necessary) for women of childbearing potential.

^bMonthly visit windows are calculated based on date of Baseline visit.

^cAt the baseline visit, only the CGI: Severity scale will be completed. CGI: Clinical Global Impressions Scale; IE: Independent Evaluator; CPT: Conners' Continuous Performance Test; CTCAE: Common Terminology Criteria for Adverse Events; DOTES: Dosage Record and Treatment Emergent Symptom Scale; SB-5: Stanford-Binet Intelligence Scales, Fifth Edition; PRN: Pro Re Nata (visits as needed).

^dMay be performed by phone or in person; #: procedures may be carried over from the double-blind Month 6 visit, if within 2 weeks of the visit.