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22q11 Deletion SyndromePhase 2NCT05290493

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

A Phase 2 study testing NB-001 in people with 22q11 Deletion Syndrome, run by Nobias Therapeutics, Inc. at 4 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 6 to 17 years
Conditions the study is for
22q11 Deletion Syndrome
What is being tested?
NB-001
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
37 participants
Where
4 sitesin 2 countries
Study dates
10 Feb 2022to 9 Jun 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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)
Show all 21Show fewer
  • 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)
  • Serum bilirubin ≤2.5 × upper limit of normal (ULN; unless documented Gilbert's Disease); aspartate aminotransferase and alanine aminotransferase ≤2.5 × ULN
  • If the subject is female and of reproductive potential, she has a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day 0.
  • If the subject is of reproductive potential, s/he agrees to abstain from reproductive cell donation, per below, and, if ever heterosexually active, to use dual effective/highly effective contraception (including at least one effective and at least one highly effective contraceptive method; Section 9.2.1) from Screening through the End of Trial Visit.
  • If the subject is female and of reproductive potential, she agrees to abstain from oocyte donation from Screening through the End of Trial Visit.
  • If the subject is male and of reproductive potential, he agrees to abstain from sperm donation from Screening through the End of Trial Visit.
  • The subject's parent/guardian understands the trial procedures and agrees to the subject's participation in the trial, as well as to the parent/guardian trial involvement, as indicated by parent/guardian signature on the informed consent form and, if applicable, subject signature on the subject assent form.

Who cannot join

  • 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.
Show all 12Show fewer
  • 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.

Trial locations and contacts

4 sites in 2 countries.

4 sites in 2 countries

United States3 sites

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Children's Hospital of Philadelphia (CHOP)

    Philadelphia, Pennsylvania, 19104

  • Seattle Children's Hospital

    Seattle, Washington, 98115

Other trials in United States

Canada1 site

  • The Hospital for Sick Children (SickKids)

    Toronto, Ontario, M5G1X8

Other trials in Canada

About this study

Official title: A Randomized, Placebo-Controlled Crossover Trial to Assess the Safety and Efficacy of NB-001 in Children and Adolescents With 22q11 Deletion Syndrome

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.

Read the 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.

Being tested
NB-001, Placebo
Keywords
22q11 Deletion Syndrome, 22q11.2 Deletion Syndrome, 22q11DS, Children and Adolescents
Medical subject headings
22q11 Deletion Syndrome, DiGeorge Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NB-001Drug

    Also called fasoracetam monohydrate, (5R)-5-(piperidine-1-carbonyl)pyrrolidin-2-one monohydrate

    Non-stimulant modulator of metabotropic glutamate receptors (mGluRs)

  • PlaceboOther

    Matching, inactive placebo

Study groups in NCT05290493
Study groupRoleWhat they receive
NB-001ExperimentalTwo (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.
Receives: Drug: NB-001
PlaceboPlacebo comparatorTwo (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.
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 6 weeks (Day 42/ET)

Secondary outcomes (6)

  1. Treatment Effect of NB-001 on the Clinical Global Impression Improvement (CGI-I) Scale

    The CGI-I scale is a 7-point scale that measures how much a patient's condition has improved or worsened over time. The CGI-I is scored on a scale of 1-7, with a score of 1 indicating "Very much improved" and 7 indicating "Very much worse". The least squares mean of the score on the CGI-I scale at the end of the 6-week treatment period is reported here.

    Measured: 6 weeks (Day 42/ET)

  2. Treatment Effect of NB-001 on the Clinical Global Impression Severity (CGI-S) Scale

    CGI-S: 7-point scale that measures a participant's overall disease severity. A 1-point improvement in the CGI-S scale is an appropriate meaningful change threshold. Possible scores are: 1 = Normal, not at all impaired; 2 = Borderline impaired; 3 = Mildly impaired; 4 = Moderately impaired; 5 = Markedly impaired; 6 = Severely impaired; 7 = Among the most extremely impaired patients.

    Measured: 6 weeks (Day 42/ET)

  3. Treatment Effect of NB-001 on the Pediatric Anxiety Rating Scale (PARS)

    The PARS is a clinician-rated instrument for assessing severity of anxiety symptoms associated with common anxiety disorders. The first section is a 50-item symptom checklist and the second section is comprised of 7 severity/impairment items reflecting the severity/impairment of all symptoms noted in the first section.

    The PARS total severity score is calculated as the sum of items 2, 3, 5, 6, and 7 from the second section of the instrument. Each item is rated on a 6-point Likert scale from 0-5 with the higher scores indicating more severe anxiety. The total severity score can range from a minimum value of 0 to a maximum value of 25. Higher scores indicate more severe anxiety.

    Additionally, per protocol, at baseline, a score of >12 on the PARS 5-item total severity score (items 2+3+5+6+7) is indicative of psychiatric symptoms in the clinical range for anxiety disorder, and a score of 10 or 11 is indicative of psychiatric symptoms in the subclinical range for anxiety disorder.

    Measured: 6 weeks (Day 42/ET)

  4. Treatment Effect of NB-001 on the Attention Deficit Hyperactivity Disorder-Rating Scale (ADHD-RS-5) - Inattention Score

    The ADHD-RS-5 is a parent/guardian reported scale to measure behaviors of children and adolescents with ADHD. It consists of 18 items grouped into two subscales: inattention (items 1-9) and hyperactivity (items 10-18). Each item is scored on a scale ranging from 0 (reflecting no symptoms) to 3 (reflecting severe symptoms). The total inattention score (reported here) can range from a minimum value of 0 to a maximum value of 27. Higher total inattention scores reflect more severe symptoms.

    Measured: 6 weeks (Day 42/ET)

  5. Treatment Effect of NB-001 on the Attention Deficit Hyperactivity Disorder-Rating Scale (ADHD-RS-5) - Hyperactivity Score

    The ADHD-RS-5 is a parent/guardian reported scale to measure behaviors of children and adolescents with ADHD. It consists of 18 items grouped into two subscales: inattention (items 1-9) and hyperactivity (items 10-18). Each item is scored on a scale ranging from 0 (reflecting no symptoms) to 3 (reflecting severe symptoms). The total hyperactivity score (reported here) can range from a minimum value of 0 to a maximum value of 27. Higher total hyperactivity scores reflect more severe symptoms.

    Measured: 6 weeks (Day 42/ET)

  6. Treatment Effect of NB-001 on the Social Responsiveness Scale, Second Edition (SRS-2)

    The SRS-2 identifies the presence and severity of social impairment within the autism spectrum. It is a 65-item, parent-completed questionnaire which incorporates 5 content areas of social deficits. The sum of all items is calculated to provide a maximum total score of 195. However, a total derived T-score is calculated centrally and reported for this trial. A higher T-score indicates more severe impairment. The population mean T-score is 50, with a standard deviation of 10. Thus, a T-score considered within the normal range is 59 or below (i.e., minimum T-score value), and a T-score indicating a severe range is 76 or above (i.e., maximum T-score value). Scores between 60-75 fall into the mild to moderate range.

    Measured: 6 weeks (Day 42/ET)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Mar 2022
  2. Study start10 Feb 2022
  3. Primary completion1 Jun 2023
  4. Study completion9 Jun 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Model description
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).
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
37 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05290493
Sponsor's protocol ID
NB-001-01
Status last verified
Jan 2025
First submitted
26 Jan 2022
Last updated
10 Feb 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing NB-001 in people with 22q11 Deletion Syndrome, run by Nobias Therapeutics, Inc. at 4 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and Tolerability of NB-001 (time frame: 6 weeks (Day 42/ET)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05290493.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2025.

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