Efficacy and Safety of NFC-1 in Adolescents With Genetic Disorders Impacting mGluR and ADHD

• ClinicalTrials.gov Identifier: NCT02777931
• Recruitment Status: Completed
• First Posted: May 19, 2016
• Results First Posted: March 29, 2018
• Last Update Posted: April 25, 2018
• Sponsor: Aevi Genomic Medicine
• Information provided by (Responsible Party): Aevi Genomic Medicine

Tracking Information

• First Submitted Date: May 13, 2016
• First Posted Date: May 19, 2016
• Results First Submitted Date: January 25, 2018
• Results First Posted Date: March 29, 2018
• Last Update Posted Date: April 25, 2018
• Study Start Date: June 2016
• Actual Primary Completion Date: February 10, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 28, 2018)

• Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale, Version 5 (ADHD-RS-5) Total Score [ Time Frame: 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 [ Time Frame: 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

• Original Primary Outcome Measures (submitted: May 18, 2016): Change from baseline in ADHD-rating scale (ADHD-RS-5) Total Score [ Time Frame: Baseline to Visit 8 (Week 6) ]
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures (submitted: May 18, 2016): Change from baseline in Clinical Global Impression - Global Improvement (CGI -I) Scale. [ Time Frame: Baseline to Visit 8 (Week 6) ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy and Safety of NFC-1 in Adolescents With Genetic Disorders Impacting mGluR and ADHD
• Official Title: A Multicenter, 6-week, Double-blind, Randomized, Placebo-controlled, Parallel-design Study to Assess the Efficacy and Safety of NFC-1 in Adolescents (Ages 12-17) With Genetic Disorders Impacting Metabotropic Glutamate Receptors and ADHD
• 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.
• 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 Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Attention Deficit Disorder With Hyperactivity

Intervention

• Drug: NFC-1
  NFC-1 is supplied as size 2 hard gelatin capsules.
  Other Name: NFC1
• Drug: Placebo
  Matching placebo capsules
  Other Name: Control

Study Arms

• Experimental: NFC-1
  Doses of NFC-1 will be administered as 100, 200, or 400 mg twice daily as capsules for oral administration.
  Intervention: Drug: NFC-1
• Placebo Comparator: Placebo
  Matching placebo capsules.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 28, 2018): 101
• Original Estimated Enrollment (submitted: May 18, 2016): 90
• Actual Study Completion Date: February 17, 2017
• Actual Primary Completion Date: February 10, 2017 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years to 17 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02777931
• Other Study ID Numbers: MDGN-NFC1-ADHD-201
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: Aevi Genomic Medicine
• Study Sponsor: Aevi Genomic Medicine
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Aevi Genomic Medicine
• Verification Date: March 2018