NB-001 in Children and Adolescents With 22q11 Deletion Syndrome

NCT05290493 | Completed Phase 2 Results FDA Drug

• 1 other identifier: NB-001-01
• Study Type: interventional
• Target: 37
• Locations: 2 countries
• Sites: 4

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.

Conditions

22q11 Deletion Syndrome

Keywords

22q11 Deletion Syndrome; 22q11.2 Deletion Syndrome; 22q11DS; Children and Adolescents

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability of NB-001

  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.

  6 weeks (Day 42/ET)

Secondary Outcomes (6)

• 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) - Inattention Score

  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)

Other Outcomes (1)

• Exit Interview

  End of Treatment; approximately 13 weeks of trial participation

Study Arms (2)

NB-001

EXPERIMENTAL

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.

Drug: NB-001

Placebo

PLACEBO COMPARATOR

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.

Other: Placebo

Interventions

NB-001 DRUG

Non-stimulant modulator of metabotropic glutamate receptors (mGluRs)

Also known as: fasoracetam monohydrate, (5R)-5-(piperidine-1-carbonyl)pyrrolidin-2-one monohydrate

NB-001

Placebo OTHER

Matching, inactive placebo

Placebo

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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
• OR:
• 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)
• ADHD-RS-5 Scores of 2 or 3 (i.e., "Often" or "Very Often") on 4 or 5 questions, with the majority of symptoms related to inattention (common in 22q11DS) rather than hyperactivity (less common in 22q11DS)
• SRS-2 of 55-59
• The subject has adequate renal and hepatic function indicated by:
• Estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 (per the revised Schwartz equation; Fadrowski and Furth 2011, Staples et al. 2010)

You may not qualify if:

• 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 1. If the subject is taking medication(s) or receiving psychotherapy, the subject and parent/guardian must agree to continue the intervention(s) at the same dose and frequency through the End of Trial Visit.
• The subject has received any investigational therapy (i.e., used for a non-approved indication and in the context of a research investigation) \<14 days prior to the first dose of NB-001 (i.e., Day 1) or within 5 drug half-lives prior to the first dose of NB-001.
• The subject uses illicit drugs (e.g., marijuana, amphetamines or cocaine), or has known alcohol or drug abuse or dependence, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (American Psychiatric Association 2013). Medically approved marijuana use, where usage is legal, is allowed; however, the dose and frequency of use should remain stable during trial participation.

Sponsors & Collaborators

• Nobias Therapeutics, Inc.: lead

Study Sites (4)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Children's Hospital of Philadelphia (CHOP)

Philadelphia, Pennsylvania, 19104, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98115, United States

Location

The Hospital for Sick Children (SickKids)

Toronto, Ontario, M5G1X8, Canada

Location

MeSH Terms

Conditions

22q11 Deletion Syndrome; DiGeorge Syndrome

Interventions

5-((2-(6-Amino-9H-purin-9-yl) ethyl) amino)-1-pentanol

Condition Hierarchy (Ancestors)

Craniofacial Abnormalities; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Lymphatic Abnormalities; Lymphatic Diseases; Hemic and Lymphatic Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Hypoparathyroidism; Parathyroid Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Patrick Dougherty
• Organization: Nobias Therapeutics, Inc.

dougherty@nobiastx.com

(215) 821-4698

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: NB-001 and matching placebo were supplied to the Investigator or designee in blinded plastic bottles, each containing 40 capsules. Additionally, subject and parent/guardian, the Investigator, clinical trial site personnel, home health nurses, centralized rater(s), and the Sponsor will be blinded to treatment sequence assignment.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects were 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). Subjects received 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 received their second treatment assignment for the subsequent 6-week period (Treatment Period 2).

Study Record Dates

• First Submitted: January 26, 2022
• First Posted: March 22, 2022
• Study Start: February 10, 2022
• Primary Completion: June 1, 2023
• Study Completion: June 9, 2023
• Last Updated: February 10, 2025
• Results First Posted: February 10, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (3)