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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT05011851




Registration number
NCT05011851
Ethics application status
Date submitted
5/08/2021
Date registered
18/08/2021
Date last updated
1/09/2021

Titles & IDs
Public title
An Open-Label Study of the Safety, Tolerability, and Pharmacokinetics of Oral NNZ-2591 in Angelman Syndrome
Scientific title
An Open-Label Study of the Safety, Tolerability, and Pharmacokinetics of Oral NNZ-2591 in Angelman Syndrome
Secondary ID [1] 0 0
NEU-2591-AS-001
Universal Trial Number (UTN)
Trial acronym
AS-001
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Angelman Syndrome 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Neurological 0 0 0 0
Other neurological disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - NNZ-2591

Experimental: NNZ-2591 - NNZ-2591 oral solution (50mg/mL) to be administered twice daily at a weight-banded dose for 13 weeks.


Treatment: Drugs: NNZ-2591
NNZ-2591 oral solution (50mg/mL) to be administered twice daily at a weight-banded dose for 13 weeks.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety and Tolerability - To examine the incidence, severity and frequency of adverse events (AEs), including serious adverse events (SAEs) during treatment with NNZ-2591.
Timepoint [1] 0 0
13 weeks
Primary outcome [2] 0 0
Pharmacokinetic - Measurement of Cmax - Maximum observed concentration (Cmax) of NNZ-2591
Timepoint [2] 0 0
13 weeks
Primary outcome [3] 0 0
Pharmacokinetic - Measurement of AUC - Area under the concentration-time curve of NNZ-2591
Timepoint [3] 0 0
13 weeks
Primary outcome [4] 0 0
Pharmacokinetic - Measurement of time to Cmax - Time to Cmax of NNZ-2591
Timepoint [4] 0 0
13 weeks
Primary outcome [5] 0 0
Pharmacokinetic - Measurement of t1/2 - Apparent terminal elimination half-life of NNZ-2591
Timepoint [5] 0 0
13 weeks
Secondary outcome [1] 0 0
Exploratory efficacy measurement - Assessed by Angelman syndrome-specific Clinical Global Impression Scale-Overall Improvement (CGI-I)
Timepoint [1] 0 0
13 weeks
Secondary outcome [2] 0 0
Exploratory efficacy measurement - Assessed by Caregiver Impression of Improvement
Timepoint [2] 0 0
13 weeks
Secondary outcome [3] 0 0
Exploratory efficacy measurement - Assessed by Angelman syndrome-specific Clinical Global Impression Scales-Domain Improvement
Timepoint [3] 0 0
13 weeks
Secondary outcome [4] 0 0
Exploratory efficacy measurement - Assessed by Angelman syndrome-specific Clinical Global Impression Scale-Severity (CGI-S)-Overall and Domain
Timepoint [4] 0 0
13 weeks
Secondary outcome [5] 0 0
Exploratory efficacy measurement - Assessed by Angelman syndrome Clinician Domain Specific Rating Scale (AS-DSRS)
Timepoint [5] 0 0
13 weeks
Secondary outcome [6] 0 0
Exploratory efficacy measurement - Assessed by Caregiver Top 3 Concerns Likert Scale
Timepoint [6] 0 0
13 weeks
Secondary outcome [7] 0 0
Exploratory efficacy measurement - Assessed by MacArthur-Bates Communicative Development Inventory (MB-CDI)
Timepoint [7] 0 0
13 weeks
Secondary outcome [8] 0 0
Exploratory efficacy measurement - Assessed by Observer-Reported Communication Ability (ORCA)
Timepoint [8] 0 0
13 weeks
Secondary outcome [9] 0 0
Exploratory efficacy measurement - Assessed by Aberrant Behavior Checklist-2 (ABC-2)
Timepoint [9] 0 0
13 weeks
Secondary outcome [10] 0 0
Exploratory efficacy measurement - Assessed by Child Sleep Habits Questionnaire (CSHQ)
Timepoint [10] 0 0
13 weeks
Secondary outcome [11] 0 0
Exploratory efficacy measurement - Assessed by Gastrointestinal Health Questionnaire (GIHQ)
Timepoint [11] 0 0
13 weeks
Secondary outcome [12] 0 0
Exploratory efficacy measurement - Assessed by Vineland Adaptive Behavior Scales-3, Interview version
Timepoint [12] 0 0
13 weeks
Secondary outcome [13] 0 0
Exploratory efficacy measurement - Assessed by Bayley Scales of Infant Development-4, Vineland Motor subscales
Timepoint [13] 0 0
13 weeks
Secondary outcome [14] 0 0
Exploratory efficacy measurement - Caregiver Diaries
Timepoint [14] 0 0
13 weeks
Secondary outcome [15] 0 0
Exploratory efficacy measurement - Assessed by Quality of Life Inventory-Disability (QI-Disability)
Timepoint [15] 0 0
13 weeks
Secondary outcome [16] 0 0
Exploratory efficacy measurement - Assessed by Impact of Childhood Neurological Disability (ICND)-Overall quality of life rating
Timepoint [16] 0 0
13 weeks

Eligibility
Key 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. Subjects with a Clinical Global Impression - Severity (CGI-S) score of 3 or greater at
the Screening visit.

4. Each subject must be able to swallow the study medication provided as a liquid
solution.

5. Caregiver(s) must have sufficient English language skills.
Minimum age
3 Years
Maximum age
17 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Mosaicism for disease-causing mutation.

2. Clinically significant abnormalities in safety laboratory tests at Screening.

3. Abnormal QTcF interval or prolongation at Screening.

4. Any other clinically significant finding (as determined by the Investigator) on ECG at
the Screening visit.

5. Excluded concomitant treatments.

6. Actively undergoing regression or loss of skills.

7. Unstable seizure profile.

8. Current clinically significant (as determined by the Investigator) cardiovascular,
renal, hepatic, gastrointestinal, respiratory, endocrine disease, or clinically
significant organ impairment.

9. Current clinically significant (as determined by the Investigator) hypo or
hyperthyroidism.

10. Type 1 or Type 2 diabetes mellitus requiring insulin (whether well controlled or
uncontrolled), or uncontrolled Type 1 or Type 2 diabetes.

11. Has planned surgery during the study.

12. History of, or current, cerebrovascular disease or brain trauma.

13. History of, or current catatonia or catatonia-like symptoms.

14. History of, or current, malignancy.

15. Current major or persistent depressive disorder (including bipolar depression).

16. Significant, uncorrected visual or uncorrected hearing impairment.

17. Allergy to strawberry.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [2] 0 0
Centre for Clinical Trials in Rare Neurodevelopmental Disorders at Children's Health Queensland Hospital and Health Service - South Brisbane
Recruitment hospital [3] 0 0
Austin Health - Heidelberg
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Neuren Pharmaceuticals Limited
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
A study of the safety, tolerability and pharmacokinetics of NNZ-2591 and measures of efficacy
in children and adolescents with Angelman syndrome
Trial website
https://clinicaltrials.gov/show/NCT05011851
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
James Shaw
Address 0 0
Neuren Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Patrick Kim
Address 0 0
Country 0 0
Phone 0 0
+61 2 9171 3267
Fax 0 0
Email 0 0
Patrick.Kim@novotech-cro.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT05011851