Angelman SyndromePhase 2AS-001NCT05011851
An Open-Label Study of the Safety, Tolerability, and Pharmacokinetics of Oral NNZ-2591 in Angelman Syndrome
A Phase 2 study testing NNZ-2591 in people with Angelman Syndrome, run by Neuren Pharmaceuticals Limited at 3 sites in Australia.
Trial summary
A study of the safety, tolerability and pharmacokinetics of NNZ-2591 and measures of efficacy in children and adolescents with Angelman syndrome Read more about this study
- Who is it for?
- Ages 3 to 17 years
- Conditions the study is for
- Angelman Syndrome
- What is being tested?
- NNZ-2591
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 3 sitesAustralia
- Study dates
- 12 Jul 2022to 16 Jul 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 3 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Clinical diagnosis of AS with a documented disease-causing genetic etiology known to impact maternally derived UBE3A expression in brain.
- Males or females aged 3-17 years
- Body Weight of >12Kg
- Subjects with a Clinical Global Impression - Severity (CGI-S) score of 3 or greater
- 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
- Each subject must be able to swallow the study medication provided as a liquid solution.
- Caregiver(s) must have sufficient English language skills.
Who cannot join
- Mosaicism for disease-causing mutation.
- Clinically Significant abnormalities in safety laboratory testing or vital signs at screening
- Abnormal QTcF interval or prolongation at Screening.
- Positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and previous COVID 19 infection with last 12 months that required hospitalization.
- Unstable or changes to Psychotropic treatment 2 weeks prior to screening .
- Excluded concomitant treatments
Show all 20Show fewer
- Actively undergoing regression or loss of skills.
- Unstable seizure profile.
- Current clinically significant renal conditions and abnormalities
- Current clinically significant cardiovascular, hepatic, gastrointestinal, respiratory, endocrine disease, or clinically significant organ impairment.
- 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.
- Has planned surgery during the study.
- History of, or current, cerebrovascular disease or brain trauma.
- History of, or current catatonia or catatonia-like symptoms.
- History of, or current, malignancy.
- Current major or persistent depressive disorder (including bipolar depression).
- Significant, uncorrected visual or uncorrected hearing impairment.
- Allergy to strawberry.
- Positive pregnancy test
- Subject is judged by the Investigator or Medical Monitor to be inappropriate for the study
Trial locations and contacts
3 sites in 1 country.
Australia3 sites
Austin Health
Heidelberg, Victoria, 3084
Sydney Children's Hospital
Randwick, New South Wales, 2031
Centre for Clinical Trials in Rare Neurodevelopmental Disorders at Children's Health Queensland Hospital and Health Service
South Brisbane, Queensland, 4101
About this study
A study of the safety, tolerability and pharmacokinetics of NNZ-2591 and measures of efficacy in children and adolescents with Angelman syndrome
Read the 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
- Conditions
- Angelman Syndrome
- Being tested
- NNZ-2591
- Keywords
- Angelman Syndrome
- Medical subject headings
- Angelman Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NNZ-2591Drug
Also called Cyclo-L-Glycyl-L-2-Allylproline
NNZ-2591 oral solution (50mg/mL) to be administered twice daily for 13 weeks.
| Study group | Role | What they receive |
|---|---|---|
| NNZ-2591 | Experimental | NNZ-2591 oral solution (50mg/mL) to be administered twice daily for 13 weeks. Receives: Drug: NNZ-2591 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability
To examine the incidence, severity and frequency of adverse events (AEs), including serious adverse events (SAEs) during treatment with NNZ-2591.
Measured: 13 weeks
Pharmacokinetic - Typical AUC24 of 30kg Child
Area under the concentration-time curve of NNZ-2591 over 24 hours
Measured: 13 weeks
Pharmacokinetic - Typical t1/2 in 30 kg Child
Apparent terminal elimination half-life of NNZ-2591
Measured: 13 weeks
Secondary outcomes (14)
Angelman syndrome-specific Clinical Global Impression Scale-Overall Improvement (CGI-I)
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
Measured: 13 weeks
Caregiver Impression of Improvement : Overall Score
Caregiver Impression of Improvement: Overall Score. Measured on a 7-point Likert scale (1-7) where lower scores are better.
Measured: 13 weeks
Angelman syndrome-specific Clinical Global Impression Scale - Severity (CGI-S): Overall Score
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.
Measured: 13 weeks
Angelman syndrome Clinician Domain Specific Rating Scale (AS-DSRS)
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.
Measured: 13 weeks
Caregiver Top 3 Concerns
Caregiver Top 3 Concerns: Change from baseline in Average Concerns Severity.
Measured: 13 weeks
MacArthur-Bates Communicative Development Inventory (MB-CDI)
MacArthur-Bates Communicative Development Inventory (MB-CDI)
Measured: 13 weeks
Observer-Reported Communication Ability (ORCA)
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
Measured: 13 weeks
Aberrant Behavior Checklist-2 (ABC-2)
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.
Measured: 13 weeks
Child Sleep Habits Questionnaire (CSHQ)
Child Sleep Habits Questionnaire (CSHQ). Change from baseline in total score. Range of scores was (33-99) with higher scores being worse
Measured: 13 weeks
Gastrointestinal Health Questionnaire (GIHQ)
Gastrointestinal Health Questionnaire (GIHQ)
Measured: 13 weeks
Vineland Adaptive Behavior Scales-3, Interview version
Vineland Adaptive Behavior Scales-3, Interview version; Composite standard score
Measured: 13 weeks
Exploratory efficacy measurement
Assessed by Bayley Scales of Infant Development-4, Vineland Motor subscales
Measured: 13 weeks
Quality of Life Inventory-Disability (QI-Disability)
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
Measured: 13 weeks
Impact of Childhood Neurological Disability (ICND)
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
Measured: 13 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2021
- Study start12 Jul 2022
- Primary completion13 May 2024
- Study completion16 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Angelman SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neuren Pharmaceuticals Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- James Shaw, Study director, Neuren Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05011851
- Sponsor's protocol ID
- NEU-2591-AS-001
- Acronym
- AS-001
- Status last verified
- Jan 2025
- First submitted
- 5 Aug 2021
- Last updated
- 31 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Study of the Safety, Tolerability, and Pharmacokinetics of Oral NNZ-2591 in Angelman Syndrome
- ClinicalTrials.gov ID
- NCT05011851
- Acronym / sponsor ID
- AS-001 / NEU-2591-AS-001
- Conditions
- Angelman Syndrome
- Keywords
- Angelman Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Neuren Pharmaceuticals LimitedIndustry (pharma, biotech, devices)
- Study start
- 12 Jul 2022 (actual)
- Primary completion
- 13 May 2024 (actual)
- Study completion
- 16 Jul 2024 (actual)
- First posted
- 18 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NNZ-2591 | Experimental | Drug: NNZ-2591NNZ-2591 oral solution (50mg/mL) to be administered twice daily for 13 weeks. |
Who may qualify
- Ages
- 3 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- Clinical diagnosis of AS with a documented disease-causing genetic etiology known to impact maternally derived UBE3A expression in brain.
- Males or females aged 3-17 years
- Body Weight of >12Kg
- Subjects with a Clinical Global Impression - Severity (CGI-S) score of 3 or greater
- 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
Key exclusion criteria (20 listed)
- Mosaicism for disease-causing mutation.
- Clinically Significant abnormalities in safety laboratory testing or vital signs at screening
- Abnormal QTcF interval or prolongation at Screening.
- Positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and previous COVID 19 infection with last 12 months that required hospitalization.
- Unstable or changes to Psychotropic treatment 2 weeks prior to screening .
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NNZ-2591Also: Cyclo-L-Glycyl-L-2-AllylprolineNNZ-2591 oral solution (50mg/mL) to be administered twice daily for 13 weeks. | Drug | NNZ-2591 |
Primary outcome
Safety and Tolerability
Time frame: 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
Time frame: 13 weeks
Area under the concentration-time curve of NNZ-2591 over 24 hours
Pharmacokinetic - Typical t1/2 in 30 kg Child
Time frame: 13 weeks
Apparent terminal elimination half-life of NNZ-2591
14 secondary outcomes
Angelman syndrome-specific Clinical Global Impression Scale-Overall Improvement (CGI-I)
Time frame: 13 weeks
Caregiver Impression of Improvement : Overall Score
Time frame: 13 weeks
Angelman syndrome-specific Clinical Global Impression Scale - Severity (CGI-S): Overall Score
Time frame: 13 weeks
Angelman syndrome Clinician Domain Specific Rating Scale (AS-DSRS)
Time frame: 13 weeks
Caregiver Top 3 Concerns
Time frame: 13 weeks
MacArthur-Bates Communicative Development Inventory (MB-CDI)
Time frame: 13 weeks
Observer-Reported Communication Ability (ORCA)
Time frame: 13 weeks
Aberrant Behavior Checklist-2 (ABC-2)
Time frame: 13 weeks
Child Sleep Habits Questionnaire (CSHQ)
Time frame: 13 weeks
Gastrointestinal Health Questionnaire (GIHQ)
Time frame: 13 weeks
Vineland Adaptive Behavior Scales-3, Interview version
Time frame: 13 weeks
Exploratory efficacy measurement
Time frame: 13 weeks
Quality of Life Inventory-Disability (QI-Disability)
Time frame: 13 weeks
Impact of Childhood Neurological Disability (ICND)
Time frame: 13 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2025.
- Individual participant dataSharing planned: No
Related trials for Angelman Syndrome
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A Natural History Study of Angelman Syndrome
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REVEAL: A Phase 3 Study of Obudanersen (ION582) in Angelman Syndrome
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James Shaw study director
Neuren Pharmaceuticals
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing NNZ-2591 in people with Angelman Syndrome, run by Neuren Pharmaceuticals Limited at 3 sites in Australia.
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 7 inclusion and 20 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 31 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Australia. 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. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 (time frame: 13 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 Jan 2025.