Clinical trial NCT05011851: An Open-Label Study of the Safety, Tolerability, and Pharmacokinetics of Oral NNZ-2591 in Angelman Syndrome
Official title: An Open-Label Study of the Safety, Tolerability, and Pharmacokinetics of Oral NNZ-2591 in Angelman Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Angelman Syndrome
Keywords: Angelman Syndrome
Lead sponsor: Neuren Pharmaceuticals Limited
Sponsor class: INDUSTRY
First posted: 2021-08-18
Enrollment: 17
Sex: ALL
Minimum age (years): 3
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Safety and Tolerability
timeFrame: 13 weeks
measure: Pharmacokinetic - Typical AUC24 of 30kg Child
timeFrame: 13 weeks
measure: Pharmacokinetic - Typical t1/2 in 30 kg Child
timeFrame: 13 weeks
Secondary outcomes:
measure: Angelman syndrome-specific Clinical Global Impression Scale-Overall Improvement (CGI-I)
timeFrame: 13 weeks
measure: Caregiver Impression of Improvement : Overall Score
timeFrame: 13 weeks
measure: Angelman syndrome-specific Clinical Global Impression Scale - Severity (CGI-S): Overall Score
timeFrame: 13 weeks
measure: Angelman syndrome Clinician Domain Specific Rating Scale (AS-DSRS)
timeFrame: 13 weeks
measure: Caregiver Top 3 Concerns
timeFrame: 13 weeks
measure: MacArthur-Bates Communicative Development Inventory (MB-CDI)
timeFrame: 13 weeks
measure: Observer-Reported Communication Ability (ORCA)
timeFrame: 13 weeks
measure: Aberrant Behavior Checklist-2 (ABC-2)
timeFrame: 13 weeks
measure: Child Sleep Habits Questionnaire (CSHQ)
timeFrame: 13 weeks
measure: Gastrointestinal Health Questionnaire (GIHQ)
timeFrame: 13 weeks
measure: Vineland Adaptive Behavior Scales-3, Interview version
timeFrame: 13 weeks
measure: Exploratory efficacy measurement
timeFrame: 13 weeks
measure: Quality of Life Inventory-Disability (QI-Disability)
timeFrame: 13 weeks
measure: Impact of Childhood Neurological Disability (ICND)
timeFrame: 13 weeks
Other outcomes:
Locations:
city: Randwick
country: Australia
facility: Sydney Children's Hospital
state: New South Wales
city: South Brisbane
country: Australia
facility: Centre for Clinical Trials in Rare Neurodevelopmental Disorders at Children's Health Queensland Hospital and Health Service
state: Queensland
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
Study officials:
affiliation: Neuren Pharmaceuticals
name: James Shaw
role: STUDY_DIRECTOR
References: