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

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

Inclusion criteria

• 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.

Exclusion criteria

• 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.
• 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