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

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

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

Study Overview

• Status: Recruiting
• Conditions: Prader-Willi Syndrome
• Intervention / Treatment: Drug: NNZ-2591

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Henry Nickson; Phone Number: +1 (470) 883-2822; Email: PWStrialreferral@precisionformedicine.com

Study Locations

• United States
  • California
    • San Diego, California, United States, 92123
      • Recruiting
      • Rady Children's Hospital San Diego
      • Contact: Phone Number: 470-883-2822; Email: PWStrialreferral@precisionformedicine.com
      • Principal Investigator: Lynne M Bird, MD
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Recruiting
      • Rare Disease Research
      • Principal Investigator: Han C Phan, MD
      • Contact: Phone Number: 470-883-2822; Email: PWStrialreferral@precisionformedicine.com
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Recruiting
      • Uncommon Cures
      • Contact: Phone Number: 470-883-2822; Email: PWStrialreferral@precisionformedicine.com
      • Principal Investigator: Roshan Lal, MD
  • Pennsylvania
    • Media, Pennsylvania, United States, 19063
      • Recruiting
      • Suburban Research
      • Principal Investigator: Shivkumar Hatti, MD
      • Contact: Phone Number: 470-883-2822; Email: PWStrialreferral@precisionformedicine.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NNZ-2591; NNZ-2591 oral solution (50mg/mL) to be administered twice daily for 13 weeks.	Drug: NNZ-2591; NNZ-2591 oral solution (50mg/mL) to be administered twice daily for 13 weeks.; Other Names: Cyclo-L-Glycyl-L-2-Allylproline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 - Measurement of Cmax	Maximum observed concentration (Cmax) of NNZ-2591	13 weeks
Pharmacokinetic - Measurement of AUC	Area under the concentration-time curve of NNZ-2591	13 weeks
Pharmacokinetic - Measurement of time to Cmax	Time to Cmax of NNZ-2591	13 weeks
Pharmacokinetic - Measurement of t1/2	Apparent terminal elimination half-life of NNZ-2591	13 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory efficacy measurement	Assessed by Child Sleep Habits Questionnaire (CSHQ)	13 weeks
Exploratory efficacy measurement	Assessed by Quality of Life Inventory-Disability (QI-Disability)	13 weeks
Exploratory efficacy measurement	Assessed by PWS-specific Clinical Global Impression Scale & Domain -Overall Improvement Score (CGI-I)	13 weeks
Exploratory efficacy measurement	Assessed by Caregiver Global Impression-Change Score	13 weeks
Exploratory efficacy measurement	Assessed by PWS-specific Clinical Global Impression Scale-Severity (CGI-S) Overall Score	13 weeks
Exploratory efficacy measurement	Assessed by Caregiver Top 3 Concerns Likert Scale Scores	13 weeks
Exploratory efficacy measurement	Assessed by PWS Profile Score	13 weeks
Exploratory efficacy measurement	Assessed by PWS Anxiousness and Distress Behaviors Questionnaire Score (PADQ)	13 weeks
Exploratory efficacy measurement	Assessed by Autism Diagnostic Observation Schedule (ADOS-2), Repetitive behaviors and Social scores	13 weeks
Exploratory efficacy measurement	Assessed by Hyperphagia Questionnaire-Clinical Trials (HQ-CT) Score	13 weeks
Exploratory efficacy measurement	Assessed by Food Safety Zone Questionnaire Score	13 weeks
Exploratory efficacy measurement	Assessed by Vineland Adaptive Behavior Scales-3 Growth Scale Scores	13 weeks
Exploratory efficacy measurement	Assessed by Zarit Burden Interview Score	13 weeks
Exploratory efficacy measurement	Assessed by Impact of Childhood Neurological Disability Scale (ICND)	13 weeks
Exploratory efficacy measurement	Assessed by Kaufman Brief Intelligence Test or Mullen Scales of Early Learning	13 weeks
Exploratory efficacy measurement	Assessed by PWS Suicidality Assessment	13 weeks
Exploratory efficacy measurement	Assessed by Caregiver Diary	13 weeks

Collaborators and Investigators

• Sponsor: Neuren Pharmaceuticals Limited
• Investigators: Study Director: Jordan Press, Neuren Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2023
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: May 18, 2023
• First Submitted That Met QC Criteria: May 18, 2023
• First Posted (Actual): May 30, 2023

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Prader-Willi Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Overnutrition; Nutrition Disorders; Overweight; Genetic Diseases, Inborn; Intellectual Disability; Abnormalities, Multiple; Chromosome Disorders; Obesity; Imprinting Disorders; Syndrome; Prader-Willi Syndrome
• Other Study ID Numbers: NEU-2591-PWS-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No