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An Open-Label Study of the Safety, Tolerability, and Pharmacokinetics of Oral NNZ-2591 in Angelman Syndrome (AS-001)

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ClinicalTrials.gov Identifier: NCT05011851
Recruitment Status : Recruiting
First Posted : August 18, 2021
Last Update Posted : August 7, 2023
Sponsor:
Information provided by (Responsible Party):
Neuren Pharmaceuticals Limited

Study Description
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Brief Summary:
A study of the safety, tolerability and pharmacokinetics of NNZ-2591 and measures of efficacy in children and adolescents with Angelman syndrome

Condition or disease Intervention/treatment Phase
Angelman Syndrome Drug: NNZ-2591 Phase 2

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
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Study of the Safety, Tolerability, and Pharmacokinetics of Oral NNZ-2591 in Angelman Syndrome
Actual Study Start Date : July 12, 2022
Estimated Primary Completion Date : June 30, 2024
Estimated Study Completion Date : June 30, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: NNZ-2591
NNZ-2591 oral solution (50mg/mL) to be administered twice daily dose for 13 weeks.
 Drug: NNZ-2591
NNZ-2591 oral solution (50mg/mL) to be administered twice daily for 13 weeks.
Other Name: Cyclo-L-Glycyl-L-2-Allylproline


Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. Pharmacokinetic - Measurement of Cmax [ Time Frame: 13 weeks ]
    Maximum observed concentration (Cmax) of NNZ-2591

  3. Pharmacokinetic - Measurement of AUC [ Time Frame: 13 weeks ]
    Area under the concentration-time curve of NNZ-2591

  4. Pharmacokinetic - Measurement of time to Cmax [ Time Frame: 13 weeks ]
    Time to Cmax of NNZ-2591

  5. Pharmacokinetic - Measurement of t1/2 [ Time Frame: 13 weeks ]
    Apparent terminal elimination half-life of NNZ-2591


Secondary Outcome Measures :
  1. Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Angelman syndrome-specific Clinical Global Impression Scale-Overall Improvement (CGI-I)

  2. Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Caregiver Impression of Change

  3. Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Angelman syndrome-specific Clinical Global Impression Scales-Domain Improvement

  4. Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Angelman syndrome-specific Clinical Global Impression Scale-Severity (CGI-S)-Overall and Domain

  5. Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Angelman syndrome Clinician Domain Specific Rating Scale (AS-DSRS)

  6. Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Caregiver Top 3 Concerns Likert Scale

  7. Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by MacArthur-Bates Communicative Development Inventory (MB-CDI)

  8. Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Observer-Reported Communication Ability (ORCA)

  9. Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Aberrant Behavior Checklist-2 (ABC-2)

  10. Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Child Sleep Habits Questionnaire (CSHQ)

  11. Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Gastrointestinal Health Questionnaire (GIHQ)

  12. Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Vineland Adaptive Behavior Scales-3, Interview version

  13. Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Bayley Scales of Infant Development-4, Vineland Motor subscales

  14. Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Caregiver Diaries

  15. Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Quality of Life Inventory-Disability (QI-Disability)

  16. Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Impact of Childhood Neurological Disability (ICND)-Overall quality of life rating


Eligibility Criteria
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Ages Eligible for Study:   3 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05011851


Contacts
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Contact: Fernanda Cecchin +61 2 9171 3274 Fernanda.Cecchin@novotech-cro.com

Locations
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Australia, New South Wales
Sydney Children's Hospital Recruiting
Randwick, New South Wales, Australia, 2031
Contact: Kaitlyn Griffin    (02) 9382 1549    kaitlyn.griffin@health.nsw.gov.au   
Australia, Queensland
Centre for Clinical Trials in Rare Neurodevelopmental Disorders at Children's Health Queensland Hospital and Health Service Recruiting
South Brisbane, Queensland, Australia, 4101
Contact: Emily Milburn    (07) 3069 7532    Emily.Milburn@health.qld.gov.au   
Australia, Victoria
Austin Health Recruiting
Heidelberg, Victoria, Australia, 3084
Contact: Greesha Zacharia    (03) 9035 7361    greesha.zacharia@unimelb.edu.au   
Sponsors and Collaborators
Neuren Pharmaceuticals Limited
Investigators
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Study Director: James Shaw Neuren Pharmaceuticals
More Information
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Responsible Party: Neuren Pharmaceuticals Limited
ClinicalTrials.gov Identifier: NCT05011851    
Other Study ID Numbers: NEU-2591-AS-001
First Posted: August 18, 2021    Key Record Dates
Last Update Posted: August 7, 2023
Last Verified: August 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Neuren Pharmaceuticals Limited:
Angelman Syndrome
Additional relevant MeSH terms:
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Angelman Syndrome
Syndrome
Disease
Pathologic Processes
Movement Disorders
Central Nervous System Diseases
 Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn
Imprinting Disorders