PART B: Efficacy and Safety of AEVI-001 in Children and Adolescents With ADHD and Without mGluR Mutations

Study Overview
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Brief Summary
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This is PART B of a 2-part, 6-week, double-blind, dose-optimization, parallel-group study in children and adolescents (ages 6-17 years) with ADHD with and without CNVs in specific genes implicated in glutamatergic signaling and neuronal activity. PART B will assess subjects who do not have CNVs in any of the specific gene mutation(s) implicated in glutamatergic signaling and neuronal connectivity.

Official Title
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A Multicenter, 2-Part, 6-Week, Double-blind, Randomized, Placebo-controlled, Parallel-design Study to Assess the Efficacy and Safety of AEVI-001 in Children and Adolescents (Ages 6-17 Years) With Attention Deficit Hyperactivity Disorder and With or Without Copy Number Variants in Specific Genes Implicated in Glutamatergic Signaling and Neuronal Connectivity

Conditions
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Attention Deficit Hyperactivity Disorder

Intervention / Treatment
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* Drug: AEVI-001
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject and parent/legally authorized representative (LAR) can speak English fluently and have provided written informed consent, and assent (as applicable) for this study. Subject is 6 to 17 years of age (inclusive) at the time of consent/assent. The date of signature of the informed consent/assent is defined as the beginning of the Screening Period. This inclusion criterion will only be assessed at the Screening Visit (Visit 1). Subject is male or non-pregnant, non-lactating female, who if of childbearing potential agrees to comply with any applicable contraceptive requirements prior to administration of investigational product (IP). Subject meets Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for a primary diagnosis of ADHD based upon DSM 5 criteria. Subject has a minimum score of ≥28 on the ADHD-RS-5 at the Baseline Visit (Visit 2). Subject has been genotyped previously and has their identity confirmed (if required). Exclusion Criteria: Subject or parent/LAR is, in the opinion of the investigator, mentally or legally incapacitated, has significant emotional problems at the time of the Screening Visit (Visit 1) which could interfere with the conduct of study evaluations. Subject has a current, controlled or uncontrolled, co-morbid major psychiatric diagnosis (aside from ADHD), including an anxiety disorder, major depression, bipolar disease, schizophrenia (or any psychotic disorder), and moderate or severe intellectual disability. Mild anxiety and/or depressive symptoms that do not meet diagnostic criteria for an anxiety disorder or major depression and/or do not require treatment are not exclusionary. Subject has autism spectrum disorder to include a DSM-IV diagnosis of autistic disorder, Asperger's disorder, or pervasive developmental disorder. Subject is currently taking any medication that might confound the results of safety assessments conducted in the study. Subject has a known history of cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, cardiac conduction problems, exercise-related cardiac events including syncope and pre-syncope, or other serious cardiac problems. Subject has any clinically significant abnormality on 12-lead ECG performed at the Screening Visit (Visit 1) and/or the Baseline Visit (Visit 2) such as serious arrhythmia, cardiac conduction problems, or other abnormalities deemed to be a potential safety issue.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AEVI-001<br> | Drug: AEVI-001<br>* Oral doses of 100 mg, 200 mg or 400 mg of AEVI-001 will be administered twice daily, during the treatment period.<br>* Other names: NFC-1;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Oral doses of Placebo will be administered twice daily, during the treatment period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale, Version 5 (ADHD-RS-5) Total Score | The ADHD-RS-5 is comprised of 18 frequency items and 12 impairment items. Each frequency item was scored on a scale from 0 = Never or rarely to 3 = Very often. The ADHD-RS-5 total score was calculated as the sum of the 18 frequency item scores. The total score ranges from 0 to 54. Higher scores indicate greater symptom severity. Change from baseline value were calculated as the assessment value minus the baseline value. | Baseline to Visit 8 (Week 6) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impression - Global Improvement (CGI -I) Response | The CGI-I item is rated on a 7-point scale from 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, 7 = Very much worse. Response is defined as achieving a CGI-I score of 1 or 2, scores of 3 to 7 or missing are defined as Non Response | Visit 3 to Visit 8 (Week 6) |