A Randomized, Placebo-Controlled Crossover Trial to Assess the Safety and Efficacy of NB-001 in Children and Adolescents With 22q11 Deletion Syndrome
Overview
- Phase
- Phase 2
- Intervention
- NB-001
- Conditions
- 22q11 Deletion Syndrome
- Sponsor
- Nobias Therapeutics, Inc.
- Enrollment
- 37
- Locations
- 4
- Primary Endpoint
- Safety and Tolerability of NB-001
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a Phase 2, randomized, placebo-controlled crossover trial to assess the safety and efficacy of NB-001 in children and adolescents with 22q11DS that manifest commonly associated neuropsychiatric symptoms.
Detailed Description
The trial is designed to allow all visits to be conducted via telephone and/or video (i.e., telemedicine) or by home health nurse. An in-person visit is required at Screening unless site or government mandates restrict this due to coronavirus disease-2019 (COVID-19). Other in-person visit(s) may occur, if indicated, based on the Investigator's clinical judgement. Subjects will be screened to confirm eligibility and then randomized in a 1:1 ratio to one of two treatment sequences: NB-001 (active drug product) followed by placebo (treatment sequence A/P) or placebo followed by NB-001 (treatment sequence P/A). During the Double-Blind Treatment Phase of the trial, the subject and/or parent/legal guardian (henceforth, 'parent/guardian') will be contacted at Day 0 to complete baseline symptom scales and will begin dosing with the investigational product (IP; NB-001 or placebo) on the morning of Day 1. Subjects or their parent/guardian will administer the IP twice daily (BID) and will be contacted at Days 0, 1, 14, 28, 42, 49, 50, 63, 77 and 91 to evaluate measures of safety and efficacy, including the completion of symptom scales. In addition, the subject and/or parent/guardian will be contacted at Days 7, 21, 35, 56, 70 and 84 to assess subject safety. Blood samples for pharmacokinetic analysis, 4β-hydroxycholesterol and plasma proline will be collected at multiple timepoints. During the Double-Blind Treatment Phase, subjects will receive IP corresponding with their first treatment assignment for 6 weeks (Treatment Period 1), followed by an intervening wash-out period of 1 week, and then will receive their second treatment assignment for the subsequent 6-week period (Treatment Period 2). All symptom scales will be centrally and/or locally administered. Approximately 10 parents/guardians and paired clinical trial site clinicians for subjects who complete the trial per protocol through Visit Day 91 will be invited to participate in an optional, one-hour (approximately), exit interview to discuss the observations of the subject's experience(s) and functioning while participating in the treatment periods of the trial. The subject and/or parent/guardian will be contacted for an End of Trial Visit to occur 4 weeks following the last dose of IP to assess safety.
Investigators
Eligibility Criteria
Inclusion Criteria
- •The subject has a genotype with a pathologic deletion in the 22q11 region confirmed by documentation (e.g., genetic test results) available at the clinical trial site.
- •The subject is aged 6 to 17 years old, inclusive.
- •The subject has a CGI-S scale score of ≥4 (i.e., moderately, markedly, severely, or among the most extremely ill patients) at Screening. Note that the Severity score of 4 could be from a composite of 2 or more sub-threshold scores.
- •And either:
- •Psychiatric symptoms in the clinical range for at least 1 of 3 disorders, anxiety disorder, ADHD, or ASD, respectively, as demonstrated by score(s) at or above the following numbers on at least 1 of 3 scales:
- •PARS 5-Item Severity Score ≥12 (i.e., sum of items 2+3+5+6+7 ≥12)
- •ADHD-RS-5 Scores of 2 or 3 (i.e., "Often" or "Very Often") on at least 6 questions, with the majority of symptoms related to inattention (common in 22q11DS) rather than hyperactivity (less common in 22q11DS)
- •SRS-2 \>60
- •Psychiatric symptoms in the subclinical range for at least 2 of 3 disorders, anxiety disorder, ADHD, and/or ASD, respectively, as demonstrated by scores at or above the following numbers on at least 2 of 3 scales:
- •PARS 5-Item Severity Score of 10 or 11 (i.e., sum of items 2+3+5+6+7=10 or 11)
Exclusion Criteria
- •The subject or parent/guardian is, in the opinion of the Investigator, mentally or legally incapacitated, or has significant emotional problems at the time of Screening or expected emotional problems during the conduct of the trial which would interfere with the conduct of the trial evaluations.
- •The subject has a history of psychotic symptoms, current psychotic symptoms, or a diagnosis of a psychotic disorder based on clinical assessment.
- •The subject has an intelligence quotient (IQ) score of \<65 based on the WASI-II assessment. NOTE: A maximum of 3 (i.e., 10% of the total N) nonverbal subjects will be allowed in the trial on a first-come-first-served basis.
- •The subject has a history of any illness that, in the opinion of the Investigator, might confound the results of the trial or pose an additional risk to the subject by participation in the trial.
- •The subject has clinically significant unstable or uncontrolled endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases.
- •The subject has uncontrolled, active seizure(s), within the 3 months prior to Screening.
- •The subject has known human immunodeficiency virus (HIV), a detectable viral load for hepatitis C, or hepatitis B surface antigen indicative of chronic active infection.
- •The subject is pregnant or is a nursing mother.
- •The subject has suicidal ideation and behavior, based on Investigator assessment of the completed Columbia-Suicide Severity Rating Scale at Screening, or when repeated on Day 0 (if more than 21 days elapse between Screening and Day 1).
- •The subject is currently taking neuropsychiatric medication(s) at a dose that has not been stable for ≥3 months prior to Day 1 or psychotherapy that has not been stable for ≥3 months prior to Day
Arms & Interventions
NB-001
Two (2) 100 mg capsules administered orally BID (400 mg total daily dose) with liquids or, if the subject is unable to swallow a capsule whole, capsules were opened, and the contents sprinkled on applesauce.
Intervention: NB-001
Placebo
Two (2) capsules (matching, inactive) administered orally BID with liquids or, if the subject is unable to swallow a capsule whole, capsules were opened, and the contents sprinkled on applesauce.
Intervention: Placebo
Outcomes
Primary Outcomes
Safety and Tolerability of NB-001
Time Frame: 6 weeks (Day 42/ET)
Type, frequency, severity, and causality of treatment-emergent adverse events (TEAEs),treatment-emergent serious adverse events (TESAEs), clinically significant changes from baseline in laboratory tests, electrocardiograms (ECGs), vital signs, and physical examination findings during treatment with NB-001.
Secondary Outcomes
- Treatment Effect of NB-001 on the Social Responsiveness Scale, Second Edition (SRS-2)(6 weeks (Day 42/ET))
- Treatment Effect of NB-001 on the Attention Deficit Hyperactivity Disorder-Rating Scale (ADHD-RS-5) - Inattention Score(6 weeks (Day 42/ET))
- Treatment Effect of NB-001 on the Clinical Global Impression Improvement (CGI-I) Scale(6 weeks (Day 42/ET))
- Treatment Effect of NB-001 on the Clinical Global Impression Severity (CGI-S) Scale(6 weeks (Day 42/ET))
- Treatment Effect of NB-001 on the Pediatric Anxiety Rating Scale (PARS)(6 weeks (Day 42/ET))
- Treatment Effect of NB-001 on the Attention Deficit Hyperactivity Disorder-Rating Scale (ADHD-RS-5) - Hyperactivity Score(6 weeks (Day 42/ET))