PART A: Efficacy and Safety of AEVI-001 in Children and Adolescents With ADHD and With mGluR Mutations

• Sponsor: Aevi Genomic Medicine, LLC, a Cerecor company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03265119
• Collaborator: (none)
• Enrollment: 69
• Location: 1
• Arms: 2
• Actual Duration (Months): 13.1
• Patients Per Site Per Month: 5.3

Study Details

Study Description

Brief Summary

This is PART A 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. Parts A will include subjects determined to have a specific gene mutations implicated in glutamatergic signaling and neuronal connectivity.

Condition or Disease	Intervention/Treatment	Phase
Attention Deficit Hyperactivity Disorder	Drug: AEVI-001; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 69 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Aug 28, 2017
• Actual Primary Completion Date: Sep 24, 2018
• Actual Study Completion Date: Oct 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AEVI-001	Drug: AEVI-001; Oral doses of 100 mg, 200 mg or 400 mg of AEVI-001 will be administered twice daily during the treatment period.; Other Names: MDGN-001 NFC-1
Placebo Comparator: Placebo	Drug: Placebo; Oral doses of 100 mg, 200 mg or 400 mg of Placebo will be administered twice daily during the treatment period.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale, Version 5 (ADHD-RS-5) Total Score [Baseline to Visit 8 (Week 6)]

   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.

Secondary Outcome Measures

1. Clinical Global Impression - Global Improvement (CGI -I) Response [Visit 8 (Week 6)]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subject and parent/legally authorized representative (LAR) can speak English fluently and have provided written informed consent, and assent (as applicable) for this study.

2. 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).

3. 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).

4. 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.

5. Subject has a minimum score of ≥28 on the ADHD-RS-5 at the Baseline Visit (Visit 2).

6. Subject has been genotyped previously and has their identity confirmed (if required).

Exclusion Criteria:

1. 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.

2. 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.

3. Subject has autism spectrum disorder to include a DSM-IV diagnosis of autistic disorder, Asperger's disorder, or pervasive developmental disorder.

4. Subject is currently taking any medication that might confound the results of safety assessments conducted in the study.

5. 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.

6. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Aevi Genomic Medicine	Wayne	Pennsylvania	United States	19087

Sponsors and Collaborators

• Aevi Genomic Medicine, LLC, a Cerecor company

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jul 25, 2018
• Statistical Analysis Plan - Sep 24, 2018

More Information

Publications

None provided.

• Responsible Party: Aevi Genomic Medicine, LLC, a Cerecor company
• ClinicalTrials.gov Identifier: NCT03265119
• Other Study ID Numbers: AEVI-001-ADHD-202
• First Posted: Aug 29, 2017
• Last Update Posted: Jul 7, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity

Study Results

Participant Flow

Arm/Group Title	AEVI-001	Placebo
Arm/Group Description	100 mg, 200 mg or 400 mg of AEVI-001 b.i.d.	Placebo b.i.d.
Period Title: Overall Study
STARTED	34	35
COMPLETED	24	28
NOT COMPLETED	10	7

Baseline Characteristics

Arm/Group Title	AEVI-001	Placebo	Total
Arm/Group Description	100 mg, 200 mg or 400 mg of AEVI-001 b.i.d.	Placebo b.i.d.	Total of all reporting groups
Overall Participants	34	35	69
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	9.9 (2.95)	10.8 (2.86)	10.4 (2.92)
Age, Customized (Count of Participants)
6 to 12 years	26 76.5%	27 77.1%	53 76.8%
13 to 17 years	8 23.5%	8 22.9%	16 23.2%
Sex: Female, Male (Count of Participants)
Female	7 20.6%	14 40%	21 30.4%
Male	27 79.4%	21 60%	48 69.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 17.6%	4 11.4%	10 14.5%
Not Hispanic or Latino	28 82.4%	31 88.6%	59 85.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 2.9%	0 0%	1 1.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	24 70.6%	20 57.1%	44 63.8%
White	7 20.6%	12 34.3%	19 27.5%
More than one race	2 5.9%	3 8.6%	5 7.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	34 100%	35 100%	69 100%
Attention Deficit Hyperactivity Disorder Rating Scale, Version 5 (ADHD-RS-5) Total Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	39.0 (6.76)	38.1 (8.29)	38.6 (7.53)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale, Version 5 (ADHD-RS-5) Total Score
Description	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.
Time Frame	Baseline to Visit 8 (Week 6)

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	AEVI-001	Placebo
Arm/Group Description	100 mg, 200 mg or 400 mg of AEVI-001 b.i.d.	Placebo b.i.d.
Measure Participants	33	34
Least Squares Mean (Standard Error) [units on a scale]	-9.17 (2.235)	-11.34 (2.122)

2. Secondary Outcome

Title	Clinical Global Impression - Global Improvement (CGI -I) Response
Description	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
Time Frame	Visit 8 (Week 6)

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	AEVI-001	Placebo
Arm/Group Description	100 mg, 200 mg or 400 mg of AEVI-001 b.i.d.	Placebo b.i.d.
Measure Participants	33	34
Count of Participants [Participants]	9 26.5%	11 31.4%

Adverse Events

Time Frame	1 year, 1 month, 4 days
Adverse Event Reporting Description	All AEs are collected from the time of the informed consent is signed until the follow-up call is completed. This includes events occurring during the screening phase of the study, regardless of whether investigational product (IP) is administered. An AE will be considered treatment emergent if it occurs after the first dose of IP and within 3 days of a subjects last dose of IP.
Arm/Group Title	AEVI-001		Placebo
Arm/Group Description	100 mg, 200 mg or 400 mg of AEVI-001 b.i.d.		Placebo b.i.d.
All Cause Mortality
	AEVI-001		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/34 (0%)		0/35 (0%)
Serious Adverse Events
	AEVI-001		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/34 (2.9%)		0/35 (0%)
Psychiatric disorders
Irritability	1/34 (2.9%)	1	0/35 (0%)	0
Other (Not Including Serious) Adverse Events
	AEVI-001		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/34 (35.3%)		11/35 (31.4%)
Gastrointestinal disorders
Abdominal pain upper	2/34 (5.9%)	2	1/35 (2.9%)	1
General disorders
Pyrexia	2/34 (5.9%)	2	0/35 (0%)	0
Fatigue	1/34 (2.9%)	1	3/35 (8.6%)	3
Infections and infestations
Upper respiratory tract infection	2/34 (5.9%)	2	1/35 (2.9%)	1
Investigations
Weight increased	4/34 (11.8%)	4	4/35 (11.4%)	4
Nervous system disorders
Headache	3/34 (8.8%)	4	4/35 (11.4%)	4
Sedation	2/34 (5.9%)	2	0/35 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The information generated by this study is the property of Aevi Genomic Medicine, Inc. Publication or other public presentation of AEVI-001 data resulting from this study requires prior review and written approval of Aevi Genomic Medicine, Inc. Abstracts, manuscripts, and presentation materials should be provided to Aevi Genomic Medicine, Inc. for review at least 30 days prior to the relevant submission deadline.