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

NCT05011851 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: NEU-2591-AS-001
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Angelman Syndrome

Keywords

Angelman Syndrome

Outcome Measures

Primary Outcomes (3)

• Safety and Tolerability

  To examine the incidence, severity and frequency of adverse events (AEs), including serious adverse events (SAEs) during treatment with NNZ-2591.

  13 weeks

• Pharmacokinetic - Typical AUC24 of 30kg Child

  Area under the concentration-time curve of NNZ-2591 over 24 hours

  13 weeks

• Pharmacokinetic - Typical t1/2 in 30 kg Child

  Apparent terminal elimination half-life of NNZ-2591

  13 weeks

Secondary Outcomes (14)

• Angelman syndrome-specific Clinical Global Impression Scale-Overall Improvement (CGI-I)

  13 weeks

• Caregiver Impression of Improvement : Overall Score

  13 weeks

• Angelman syndrome-specific Clinical Global Impression Scale - Severity (CGI-S): Overall Score

  13 weeks

• Angelman syndrome Clinician Domain Specific Rating Scale (AS-DSRS)

  13 weeks

• Caregiver Top 3 Concerns

  13 weeks

Study Arms (1)

NNZ-2591

EXPERIMENTAL

NNZ-2591 oral solution (50mg/mL) to be administered twice daily for 13 weeks.

Drug: NNZ-2591

Interventions

NNZ-2591 DRUG

NNZ-2591 oral solution (50mg/mL) to be administered twice daily for 13 weeks.

Also known as: Cyclo-L-Glycyl-L-2-Allylproline

NNZ-2591

Eligibility Criteria

• Age: 3 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Neuren Pharmaceuticals Limited: lead

Study Sites (3)

Sydney Children's Hospital

Randwick, New South Wales, 2031, Australia

Location

Centre for Clinical Trials in Rare Neurodevelopmental Disorders at Children's Health Queensland Hospital and Health Service

South Brisbane, Queensland, 4101, Australia

Location

Austin Health

Heidelberg, Victoria, 3084, Australia

Location

MeSH Terms

Conditions

Angelman Syndrome

Interventions

cyclo-L-glycyl-L-2-allylproline

Condition Hierarchy (Ancestors)

Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Imprinting Disorders

Study Officials

• James Shaw

  Neuren Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2021
• First Posted: August 18, 2021
• Study Start: July 12, 2022
• Primary Completion: May 13, 2024
• Study Completion: July 16, 2024
• Last Updated: January 31, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

AU (3)