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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

Tracking Information
First Submitted Date  ICMJE August 5, 2021
First Posted Date  ICMJE August 18, 2021
Last Update Posted Date August 7, 2023
Actual Study Start Date  ICMJE July 12, 2022
Estimated Primary Completion Date June 30, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 26, 2021)
  • 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 - Measurement of Cmax [ Time Frame: 13 weeks ]
    Maximum observed concentration (Cmax) of NNZ-2591
  • Pharmacokinetic - Measurement of AUC [ Time Frame: 13 weeks ]
    Area under the concentration-time curve of NNZ-2591
  • Pharmacokinetic - Measurement of time to Cmax [ Time Frame: 13 weeks ]
    Time to Cmax of NNZ-2591
  • Pharmacokinetic - Measurement of t1/2 [ Time Frame: 13 weeks ]
    Apparent terminal elimination half-life of NNZ-2591
Original Primary Outcome Measures  ICMJE
 (submitted: August 13, 2021)
  • 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 - Measurement of Cmax [ Time Frame: 13 weeks ]
    Maximum observed concentration (Cmax) of NNZ-2591
  • Pharmacokinetic - Measurement of AUC∞ [ Time Frame: 13 weeks ]
    Area under the concentration-time curve from time 0 to infinity of NNZ-2591
  • Pharmacokinetic - Measurement of time to Cmax [ Time Frame: 13 weeks ]
    Time to Cmax of NNZ-2591
  • Pharmacokinetic - Measurement of t1/2 [ Time Frame: 13 weeks ]
    Apparent terminal elimination half-life of NNZ-2591
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 11, 2022)
  • Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Angelman syndrome-specific Clinical Global Impression Scale-Overall Improvement (CGI-I)
  • Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Caregiver Impression of Change
  • Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Angelman syndrome-specific Clinical Global Impression Scales-Domain Improvement
  • Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Angelman syndrome-specific Clinical Global Impression Scale-Severity (CGI-S)-Overall and Domain
  • Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Angelman syndrome Clinician Domain Specific Rating Scale (AS-DSRS)
  • Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Caregiver Top 3 Concerns Likert Scale
  • Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by MacArthur-Bates Communicative Development Inventory (MB-CDI)
  • Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Observer-Reported Communication Ability (ORCA)
  • Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Aberrant Behavior Checklist-2 (ABC-2)
  • Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Child Sleep Habits Questionnaire (CSHQ)
  • Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Gastrointestinal Health Questionnaire (GIHQ)
  • Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Vineland Adaptive Behavior Scales-3, Interview version
  • Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Bayley Scales of Infant Development-4, Vineland Motor subscales
  • Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Caregiver Diaries
  • Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Quality of Life Inventory-Disability (QI-Disability)
  • Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Impact of Childhood Neurological Disability (ICND)-Overall quality of life rating
Original Secondary Outcome Measures  ICMJE
 (submitted: August 13, 2021)
  • Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Angelman syndrome-specific Clinical Global Impression Scale-Overall Improvement (CGI-I)
  • Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Caregiver Impression of Improvement
  • Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Angelman syndrome-specific Clinical Global Impression Scales-Domain Improvement
  • Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Angelman syndrome-specific Clinical Global Impression Scale-Severity (CGI-S)-Overall and Domain
  • Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Angelman syndrome Clinician Domain Specific Rating Scale (AS-DSRS)
  • Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Caregiver Top 3 Concerns Likert Scale
  • Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by MacArthur-Bates Communicative Development Inventory (MB-CDI)
  • Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Observer-Reported Communication Assessment (ORCA)
  • Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Aberrant Behavior Checklist-2 (ABC-2)
  • Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Child Sleep Habits Questionnaire (CSHQ)
  • Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Gastrointestinal Health Questionnaire (GIHQ)
  • Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Vineland Adaptive Behavior Scales-3, Interview version
  • Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Bayley Scales of Infant Development-4, Vineland Motor subscales
  • Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Caregiver Assessments/Diaries
  • Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Quality of Life Inventory-Disability (QI-Disability)
  • Exploratory efficacy measurement [ Time Frame: 13 weeks ]
    Assessed by Impact of Childhood Neurological Disability (ICND)-Overall quality of life rating
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE An Open-Label Study of the Safety, Tolerability, and Pharmacokinetics of Oral NNZ-2591 in Angelman Syndrome
Official Title  ICMJE An Open-Label Study of the Safety, Tolerability, and Pharmacokinetics of Oral NNZ-2591 in 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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Angelman Syndrome
Intervention  ICMJE 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
Study Arms  ICMJE Experimental: NNZ-2591
NNZ-2591 oral solution (50mg/mL) to be administered twice daily dose for 13 weeks.
Intervention: Drug: NNZ-2591
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 13, 2021)		 20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2024
Estimated Primary Completion Date June 30, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 3 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Fernanda Cecchin +61 2 9171 3274 Fernanda.Cecchin@novotech-cro.com
Listed Location Countries  ICMJE Australia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05011851
Other Study ID Numbers  ICMJE NEU-2591-AS-001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Neuren Pharmaceuticals Limited
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Neuren Pharmaceuticals Limited
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: James Shaw Neuren Pharmaceuticals
PRS Account Neuren Pharmaceuticals Limited
Verification Date August 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP