Revised development strategy

A study of the safety, tolerability and pharmacokinetics of NNZ-2591 and measures of efficacy in children and adolescents with Prader-Willi Syndrome.

The primary purpose of this study is to investigate the safety, tolerability and pharmacokinetics of treatment with NNZ-2591 oral solution in children and adolescents with Prader-Willi Syndrome. The secondary purpose is to investigate measures of efficacy. Subjects will receive treatment with NNZ-2591 oral solution (50 mg/mL) doses for a total of 13 weeks.

Inclusion Criteria:

1. Clinical diagnosis of PWS with a documented disease-causing genetic abnormality of the chromosome 15q11-q13 confirmed by DNA methylation and microarray.
2. Males or females aged 4-12 years, inclusive.
3. Body weight of 12 kg to 100kg (inclusive) at Baseline.
4. Subjects with a Clinical Global Impression - Severity (CGI-S) score of 4 or greater at the Screening visit.
5. Must currently be on treatment with growth hormone.
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.
8. Subject and caregiver must reside in the US and have been resident in the US for at least 3 months prior to screening.

Exclusion Criteria:

1. Body weight <12 kg or >100 kg at Baseline.
2. HbA1c values above 7% at the Screening visit.
3. Clinically significant abnormalities in safety laboratory tests and vital signs at Screening.
4. Positive pregnancy test at the Screening visit.
5. Positive drugs of abuse screen not explained by concomitant medications.
6. Abnormal QTcF interval or prolongation at Screening.
7. Any other clinically significant finding on ECG at the Screening visit.
8. Positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at Screening or Baseline.
9. Previous COVID 19 infection with last 12 months that required hospitalization.
10. Previous COVD-19 infection involving multi-organ systems, resulting in Multisystem Inflammatory Syndrome in Children (MIS-C) or with clinically significant long term effects.
11. COVID-19 infection associated with acute kidney injury (AKI) or renal conditions.
12. Renal conditions or abnormalities identified in laboratory testing, imaging or medical history.
13. Liver conditions and Hepatic abnormalities.
14. Vision abnormalities and Ocular conditions.
15. Excluded concomitant treatments.
16. Unstable seizure profile.
17. Current clinically significant cardiovascular, gastrointestinal, or respiratory disease, or clinically significant organ impairment, or endocrine disease with the exception of obesity and controlled hypothyroidism.
18. 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.
19. Has planned surgery during the study.
20. History of, or current, cerebrovascular disease or brain trauma.
21. History of, or current catatonia or catatonia-like symptoms.
22. History of, or current, malignancy.
23. Current major or persistent depressive disorder (including bipolar depression).
24. Significant uncorrected hearing impairment.
25. Allergy to strawberry.
26. Has participated in another interventional clinical study within 30 days prior to start of Screening.
27. Subject is judged by the Investigator or Medical Monitor to be inappropriate for the study.