Angelman Syndrome
Conditions
Keywords
Angelman Syndrome
Brief summary
A study of the safety, tolerability and pharmacokinetics of NNZ-2591 and measures of efficacy in children and adolescents with Angelman syndrome
Detailed description
The primary purpose of this study is to investigate the safety, tolerability and pharmacokinetics of treatment with NNZ-2591 oral solution, 50mg/L, in children and adolescents with Angelman syndrome. The secondary purpose is to investigate measures of efficacy of subjects will receive treatment of 50mg/mL orally administered NNZ-2591 for a total of 13 weeks
Interventions
DRUGNNZ-2591
NNZ-2591 oral solution (50mg/mL) to be administered twice daily for 13 weeks.
Sponsors
Neuren Pharmaceuticals Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. Clinical diagnosis of AS with a documented disease-causing genetic etiology known to impact maternally derived UBE3A expression in brain. 2. Males or females aged 3-17 years 3. Body Weight of \>12Kg 4. Subjects with a Clinical Global Impression - Severity (CGI-S) score of 3 or greater 5. Not actively undergoing regression or loss of skills, defined as no persistent loss of previously acquired developmental skills for a period within 3 months of the Screening visit 6. Each subject must be able to swallow the study medication provided as a liquid solution. 7. Caregiver(s) must have sufficient English language skills.
Exclusion criteria
1. Mosaicism for disease-causing mutation. 2. Clinically Significant abnormalities in safety laboratory testing or vital signs at screening 3. Abnormal QTcF interval or prolongation at Screening. 4. Positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and previous COVID 19 infection with last 12 months that required hospitalization. 5. Unstable or changes to Psychotropic treatment 2 weeks prior to screening . 6. Excluded concomitant treatments 7. Actively undergoing regression or loss of skills. 8. Unstable seizure profile. 9. Current clinically significant renal conditions and abnormalities 10. Current clinically significant cardiovascular, hepatic, gastrointestinal, respiratory, endocrine disease, or clinically significant organ impairment. 11. Current clinically significant hypo or hyperthyroidism, Type 1 or Type 2 diabetes mellitus requiring insulin (whether well controlled or uncontrolled), or uncontrolled Type 1 or Type 2 diabetes. 12. Has planned surgery during the study. 13. History of, or current, cerebrovascular disease or brain trauma. 14. History of, or current catatonia or catatonia-like symptoms. 15. History of, or current, malignancy. 16. Current major or persistent depressive disorder (including bipolar depression). 17. Significant, uncorrected visual or uncorrected hearing impairment. 18. Allergy to strawberry. 19. Positive pregnancy test 20. Subject is judged by the Investigator or Medical Monitor to be inappropriate for the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability | 13 weeks | To examine the incidence, severity and frequency of adverse events (AEs), including serious adverse events (SAEs) during treatment with NNZ-2591. |
| Pharmacokinetic - Typical AUC24 of 30kg Child | 13 weeks | Area under the concentration-time curve of NNZ-2591 over 24 hours |
| Pharmacokinetic - Typical t1/2 in 30 kg Child | 13 weeks | Apparent terminal elimination half-life of NNZ-2591 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Angelman syndrome Clinician Domain Specific Rating Scale (AS-DSRS) | 13 weeks | Angelman syndrome Clinician Domain Specific Rating Scale (AS-DSRS). Change from baseline in total score based on a 5-point Likert scale (0-4) where lower scores are better. |
| Caregiver Top 3 Concerns | 13 weeks | Caregiver Top 3 Concerns: Change from baseline in Average Concerns Severity. |
| MacArthur-Bates Communicative Development Inventory (MB-CDI) | 13 weeks | MacArthur-Bates Communicative Development Inventory (MB-CDI) |
| Observer-Reported Communication Ability (ORCA) | 13 weeks | Observer-Reported Communication Ability (ORCA). Change from baseline in modified t-score. Scores range from 25.8 - 83.8 with higher scores indicating greater communication abililty. A positive change from baseline indicates improvement |
| Aberrant Behavior Checklist-2 (ABC-2) | 13 weeks | Aberrant Behavior Checklist-2 (ABC-2) - Change from baseline in total score. Higher scores indicate more behavioral issues. A negative change from baseline indicates improvement. |
| Angelman syndrome-specific Clinical Global Impression Scale-Overall Improvement (CGI-I) | 13 weeks | Assessed by Angelman syndrome-specific Clinical Global Impression Scale-Overall Improvement (CGI-I). Score on a Likert scale (1-7) where lower scores are better |
| Gastrointestinal Health Questionnaire (GIHQ) | 13 weeks | Gastrointestinal Health Questionnaire (GIHQ) |
| Vineland Adaptive Behavior Scales-3, Interview version | 13 weeks | Vineland Adaptive Behavior Scales-3, Interview version; Composite standard score |
| Exploratory efficacy measurement | 13 weeks | Assessed by Bayley Scales of Infant Development-4, Vineland Motor subscales |
| Quality of Life Inventory-Disability (QI-Disability) | 13 weeks | Quality of Life Inventory-Disability (QI-Disability). Change from baseline inoverall score. Scores range from 0-100 with higher scores indicating better quality of life. A positive change indicates improvement |
| Impact of Childhood Neurological Disability (ICND) | 13 weeks | Impact of Childhood Neurological Disability (ICND): Change from baseline in overall quality of life rating. Scores range from 1-6, with a higher score indicating better quality of life. A positive change from baseline indicates improvement |
| Child Sleep Habits Questionnaire (CSHQ) | 13 weeks | Child Sleep Habits Questionnaire (CSHQ). Change from baseline in total score. Range of scores was (33-99) with higher scores being worse |
| Caregiver Impression of Improvement : Overall Score | 13 weeks | Caregiver Impression of Improvement: Overall Score. Measured on a 7-point Likert scale (1-7) where lower scores are better. |
| Angelman syndrome-specific Clinical Global Impression Scale - Severity (CGI-S): Overall Score | 13 weeks | Angelman syndrome-specific Clinical Global Impression Scale-Severity (CGI-S): Change from baseline on overall score based on a 7-point Likert scale (1-7) where lower scores are better. |
Countries
Australia
Outcome results
None listed