An Open-Label Study of Oral NNZ-2591 in Prader-Willi Syndrome (PWS-001)

Prader-Willi Syndrome Clinical Trial

— PWS-001  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05879614
• Other study ID #: NEU-2591-PWS-001
• Status: Recruiting
• Phase: Phase 2
• Start date: September 1, 2023
• Est. completion date: June 30, 2024

Study information

• Verified date: February 2024
• Source: Neuren Pharmaceuticals Limited
• Contact: Henry Nickson
• Phone: +1 (470) 883-2822
• Email: PWStrialreferral[@]precisionformedicine.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: June 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 12 Years

Eligibility

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.

Related Conditions & MeSH terms

• Prader-Willi Syndrome
• Syndrome

Intervention

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

Locations

Country	Name	City	State
United States	Rare Disease Research	Atlanta	Georgia
United States	Uncommon Cures	Chevy Chase	Maryland
United States	Suburban Research	Media	Pennsylvania
United States	Rady Children's Hospital San Diego	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Neuren Pharmaceuticals Limited

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Pharmacokinetic - Measurement of Cmax	Maximum observed concentration (Cmax) of NNZ-2591	13 weeks
Primary	Pharmacokinetic - Measurement of AUC	Area under the concentration-time curve of NNZ-2591	13 weeks
Primary	Pharmacokinetic - Measurement of time to Cmax	Time to Cmax of NNZ-2591	13 weeks
Primary	Pharmacokinetic - Measurement of t1/2	Apparent terminal elimination half-life of NNZ-2591	13 weeks
Secondary	Exploratory efficacy measurement	Assessed by PWS-specific Clinical Global Impression Scale & Domain -Overall Improvement Score (CGI-I)	13 weeks
Secondary	Exploratory efficacy measurement	Assessed by Caregiver Global Impression-Change Score	13 weeks
Secondary	Exploratory efficacy measurement	Assessed by PWS-specific Clinical Global Impression Scale-Severity (CGI-S) Overall Score	13 weeks
Secondary	Exploratory efficacy measurement	Assessed by Caregiver Top 3 Concerns Likert Scale Scores	13 weeks
Secondary	Exploratory efficacy measurement	Assessed by PWS Profile Score	13 weeks
Secondary	Exploratory efficacy measurement	Assessed by PWS Anxiousness and Distress Behaviors Questionnaire Score (PADQ)	13 weeks
Secondary	Exploratory efficacy measurement	Assessed by Autism Diagnostic Observation Schedule (ADOS-2), Repetitive behaviors and Social scores	13 weeks
Secondary	Exploratory efficacy measurement	Assessed by Hyperphagia Questionnaire-Clinical Trials (HQ-CT) Score	13 weeks
Secondary	Exploratory efficacy measurement	Assessed by Food Safety Zone Questionnaire Score	13 weeks
Secondary	Exploratory efficacy measurement	Assessed by Vineland Adaptive Behavior Scales-3 Growth Scale Scores	13 weeks
Secondary	Exploratory efficacy measurement	Assessed by Zarit Burden Interview Score	13 weeks
Secondary	Exploratory efficacy measurement	Assessed by Child Sleep Habits Questionnaire (CSHQ)	13 weeks
Secondary	Exploratory efficacy measurement	Assessed by Impact of Childhood Neurological Disability Scale (ICND)	13 weeks
Secondary	Exploratory efficacy measurement	Assessed by Quality of Life Inventory-Disability (QI-Disability)	13 weeks
Secondary	Exploratory efficacy measurement	Assessed by Kaufman Brief Intelligence Test or Mullen Scales of Early Learning	13 weeks
Secondary	Exploratory efficacy measurement	Assessed by PWS Suicidality Assessment	13 weeks
Secondary	Exploratory efficacy measurement	Assessed by Caregiver Diary	13 weeks