An Open-Label Study of Oral NNZ-2591 in Phelan-McDermid Syndrome (PMS-001)

Neuren Pharmaceuticals Limited18 enrolled

Overview

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

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Phelan-McDermid Syndrome

Interventions

NNZ-2591DRUG

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

Eligibility

Sex: ALLMin age: 3 YearsMax age: 12 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Clinical diagnosis of PMS with a documented disease-causing genetic abnormality of SHANK3. 2. Males or females aged 3-12 years. 3. Body weight of 12 kg or higher at Screening. 4. Subjects with a Clinical Global Impression - Severity (CGI-S) score of 4 or greater at the Screening visit. 5. 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 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. Exclusion Criteria: 1. Body weight \< 12kg at screening 2. Clinically significant abnormalities in safety laboratory tests and vital signs at Screening. 3. Abnormal QTcF interval or prolongation at Screening. 4. Any other clinically significant finding on ECG at the Screening visit. 5. Positive for severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) and previous COVID 19 infection with last 12 months that required hospitalization 6. Unstable or changes Psychotropic treatment 2 weeks prior to screening . 7. Excluded concomitant treatments. 8. Actively undergoing regression or loss of skills. 9. Unstable seizure profile. 10. Current clinically significant renal conditions and abnormalities 11. Current clinically significant cardiovascular, renal, hepatic, gastrointestinal, respiratory, endocrine disease, or clinically significant organ impairment. 12. 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. 13. Has planned surgery during the study. 14. History of, or current, cerebrovascular disease or brain trauma. 15. History of, or current catatonia or catatonia-like symptoms. 16. History of, or current, malignancy. 17. Current major or persistent depressive disorder (including bipolar depression). 18. Significant, uncorrected visual or uncorrected hearing impairment. 19. Allergy to strawberry. 20. Positive pregnancy test 21. Subject is judged by the Investigator or Medical Monitor to be inappropriate for the study

Locations (4)

Rush University Medical Center

Chicago, Illinois, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Boston Children's Hospital

Boston, Massachusetts, United States

Texas Children's Hospital

Houston, Texas, United States

Outcomes

Primary Outcomes

Safety and Tolerability

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

Time frame: 13 weeks

Pharmacokinetic - Mean AUC24

Approximately nine sparse pharmacokinetic (PK) samples were collected from each participant under steady-state conditions. These samples were taken at pre-dose, 1-3 hours post-dose, and/or 4-7 hours post-dose during Weeks 2, 6, and 13. The individual pharmacokinetic parameters for NNZ-2591, including half-life (t1/2) and area under the curve over 24 hours (AUC24), were derived using subject-level concentration-time profiles from the study population model.

Time frame: Pre-dose, 1-3 h post-dose and/or 4-7 h post-dose at Weeks 2, 6 and 13.

Pharmacokinetic - t1/2

Time frame: Pre-dose, 1-3 h post-dose and/or 4-7 h post-dose at Weeks 2, 6 and 13.

Secondary Outcomes

CGI-I

Phelan-McDermid Syndrome-specific Clinical Global Impression of Improvement Scale (CGI-I) - Overall Improvement Score on a 7 point Likert scale (1-7) where lower scores are better.

Time frame: CGI-I was assessed at Weeks 6, 13/EOT & 15. Overall improvement scores relate to Week 13/EOT visit.

CIC

Caregiver Impression of Improvement: Measured on a 7 point Likert scale (1-7) where lower scores are better.

Data from ClinicalTrials.gov

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