Efficacy and Safety of NFC-1 in Adolescents With Genetic Disorders Impacting mGluR and ADHD
Study Details
Study Description
Brief Summary
This is a randomized, double-blind, placebo-controlled, parallel-group study of NFC-1 versus placebo in adolescents with ADHD who have genetic disorders impacting mGluRs.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
Detailed Description
This is a randomized, double-blind, placebo-controlled, parallel-group study of adolescents with ADHD who have genetic disorders impacting mGluRs. Approximately 90 subjects will receive randomized treatment with NFC-1 or placebo. Dosing will be optimized during the first 4 weeks of treatment, based on clinical response and tolerability, and maintained for an additional 2 weeks.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: NFC-1 Doses of NFC-1 will be administered as 100, 200, or 400 mg twice daily as capsules for oral administration. |
Drug: NFC-1
NFC-1 is supplied as size 2 hard gelatin capsules.
Other Names:
|
| Placebo Comparator: Placebo Matching placebo capsules. |
Drug: Placebo
Matching placebo capsules
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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.
- Clinical Global Impression - Global Improvement (CGI -I) Response [Visit 3 to 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
Inclusion Criteria:
-
Subject has ADHD as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) and Version 5 of the Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-5) ≥ 28 at Baseline with or without conventional ADHD therapy.
-
Subject has an intelligence quotient (IQ) > 79, based on the Wechsler Abbreviated Scale of Intelligence, second edition (WASI-II).
-
Subject has been genotyped previously and determined to have disruptive mutations in genes within the glutamate receptor metabotropic (GRM)-network as determined by the presence of copy number variations (CNVs) (GRM biomarker-positive subjects). The confirmation of a subject's positive status will be provided by the sponsor.
-
Subject is judged to be in general good health, other than having ADHD, based on medical history, physical examination, vital signs measurements, laboratory safety tests, and the Columbia Suicide Severity Rating Scale (C-SSRS) performed at the Screening Visit and/or prior to administration of investigational product (IP).
-
Subject has no clinically significant abnormality on electrocardiogram (ECG) performed at the Screening Visit and/or prior to administration of IP such as serious arrhythmia, bradycardia, tachycardia, cardiac conduction problems, or other abnormalities deemed to be a potential safety issue.
-
Parent/legal guardian and subject understand the study procedures and agree to the subject's participation in the study as indicated by parental/legal guardian signature on the subject informed consent form and subject signature on the assent form.
Exclusion Criteria:
-
Subjects with prior diagnosis of comorbid major psychiatric disorders (ie, aside from ADHD), including major depression, bipolar disease, schizophrenia, pervasive development disorder, and intellectual disability.
-
Subject is currently taking a prohibited medication and/or is unwilling to wean off current ADHD medication to participate in the study
-
Subject has a history of any illness that in the opinion of the study investigator might confound the results of the study or poses an additional risk to the subject by his or her participation in the study.
-
Subject has a known history or presence of syncope, cardiac conduction problems (eg, clinically significant heart block), exercise-related cardiac events including syncope and pre-syncope, or clinically significant bradycardia.
-
Subject has a history of stroke, chronic seizures, or major neurological disorder which, in the opinion of the investigator, would interfere with the subject's ability to participate and/or be evaluated in the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Clinical Trials Center at Kennedy Krieger Institute | Baltimore | Maryland | United States | 21205 |
Sponsors and Collaborators
- Aevi Genomic Medicine, LLC, a Cerecor company
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.- MDGN-NFC1-ADHD-201
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | NFC-1 | Placebo |
|---|---|---|
| Arm/Group Description | Doses of NFC-1 will be administered as 100, 200, or 400 mg twice daily as capsules (size 2 hard gelatin capsules). | Matching placebo capsules |
| Period Title: Overall Study | ||
| STARTED | 49 | 52 |
| Safety Population | 47 | 50 |
| Modified Intent to Treat Population | 46 | 50 |
| COMPLETED | 37 | 39 |
| NOT COMPLETED | 12 | 13 |
Baseline Characteristics
| Arm/Group Title | NFC-1 | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | Doses of NFC-1 will be administered as 100, 200, or 400 mg twice daily as capsules (size 2 hard gelatin capsules). | Matching placebo capsules | Total of all reporting groups |
| Overall Participants | 47 | 50 | 97 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
13.8
(1.40)
|
14.4
(1.68)
|
14.1
(1.58)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
21
44.7%
|
15
30%
|
36
37.1%
|
| Male |
26
55.3%
|
35
70%
|
61
62.9%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
1
2.1%
|
1
2%
|
2
2.1%
|
| Asian |
0
0%
|
1
2%
|
1
1%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
11
23.4%
|
18
36%
|
29
29.9%
|
| White |
29
61.7%
|
26
52%
|
55
56.7%
|
| More than one race |
6
12.8%
|
3
6%
|
9
9.3%
|
| Unknown or Not Reported |
0
0%
|
1
2%
|
1
1%
|
| Region of Enrollment (Count of Participants) | |||
| United States |
47
100%
|
50
100%
|
97
100%
|
Outcome Measures
| 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 |
|---|
| Modified Intent to Treat Population = all randomized subjects who took at least one dose of randomized study drug and have a valid baseline assessment and at least 1 valid post baseline assessment. |
| Arm/Group Title | NFC-1 | Placebo |
|---|---|---|
| Arm/Group Description | Doses of NFC-1 will be administered as 100, 200, or 400 mg twice daily as capsules (size 2 hard gelatin capsules). | Matching placebo capsules |
| Measure Participants | 46 | 50 |
| Least Squares Mean (Standard Error) [units on a scale] |
-14.2
(1.82)
|
-12.1
(1.75)
|
| 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 3 to Visit 8 (Week 6) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Modified Intent to Treat Population = all randomized subjects who took at least one dose of randomized study drug and have a valid baseline assessment and at least 1 valid post baseline assessment. |
| Arm/Group Title | NFC-1 | Placebo |
|---|---|---|
| Arm/Group Description | Doses of NFC-1 will be administered as 100, 200, or 400 mg twice daily as capsules (size 2 hard gelatin capsules). | Matching placebo capsules |
| Measure Participants | 46 | 50 |
| Count of Participants [Participants] |
26
55.3%
|
16
32%
|
Adverse Events
| Time Frame | 8 months, 5 days | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | NFC-1 | Placebo | ||
| Arm/Group Description | Doses of NFC-1 will be administered as 100, 200, or 400 mg twice daily as capsules (size 2 hard gelatin capsules). | Matching placebo capsules | ||
All Cause Mortality |
||||
| NFC-1 | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/47 (0%) | 0/50 (0%) | ||
Serious Adverse Events |
||||
| NFC-1 | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/47 (0%) | 0/50 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| NFC-1 | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 33/47 (70.2%) | 28/50 (56%) | ||
| Gastrointestinal disorders | ||||
| Nausea | 3/47 (6.4%) | 3 | 4/50 (8%) | 4 |
| General disorders | ||||
| Fatigue | 7/47 (14.9%) | 7 | 3/50 (6%) | 3 |
| Infections and infestations | ||||
| Nasopharyngitis | 1/47 (2.1%) | 1 | 4/50 (8%) | 4 |
| Upper respiratory tract infection | 2/47 (4.3%) | 2 | 5/50 (10%) | 5 |
| Injury, poisoning and procedural complications | ||||
| Accidental overdose | 5/47 (10.6%) | 7 | 3/50 (6%) | 3 |
| Investigations | ||||
| Weight increase | 7/47 (14.9%) | 7 | 2/50 (4%) | 2 |
| Metabolism and nutrition disorders | ||||
| Increased appetite | 3/47 (6.4%) | 3 | 2/50 (4%) | 2 |
| Nervous system disorders | ||||
| Headache | 4/47 (8.5%) | 5 | 5/50 (10%) | 10 |
| Psychiatric disorders | ||||
| Irritability | 1/47 (2.1%) | 1 | 3/50 (6%) | 3 |
Limitations/Caveats
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 Medgenics. Publication or other public presentation of NFC-1 data resulting from this study requires prior review and written approval of Medgenics. Abstracts, manuscripts, and presentation materials should be provided to Medgenics for review at least 30 days prior to the relevant submission deadline.
Results Point of Contact
| Name/Title | Garry A Neil, MD |
|---|---|
| Organization | Aevi Genomic Medicine |
| Phone | 610-254-4208 |
| garry.neil@aevigenomics.com |
- MDGN-NFC1-ADHD-201