An Open-Label Study of Oral NNZ-2591 in Phelan-McDermid Syndrome (PMS-001)
- Registration Number
- NCT05025241
- Lead Sponsor
- Neuren Pharmaceuticals Limited
- Brief Summary
A study of the safety, tolerability and pharmacokinetics of NNZ-2591 and measures of efficacy in children and adolescents with Phelan-McDermid Syndrome.
- 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 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 18
- Clinical diagnosis of PMS with a documented disease-causing genetic abnormality of SHANK3.
- Males or females aged 3-12 years.
- Body weight of 12 kg or higher at Screening.
- Subjects with a Clinical Global Impression - Severity (CGI-S) score of 4 or greater at the Screening visit.
- 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.
- Body weight < 12kg at screening
- Clinically significant abnormalities in safety laboratory tests and vital signs at Screening.
- Abnormal QTcF interval or prolongation at Screening.
- Any other clinically significant finding on ECG at the Screening visit.
- Positive for severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) and previous COVID 19 infection with last 12 months that required hospitalization
- Unstable or changes 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, renal, 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description NNZ-2591 NNZ-2591 NNZ-2591 oral solution (50mg/mL) to be administered twice daily dose for 13 weeks.
- Primary Outcome Measures
Name Time Method Safety and Tolerability 13 weeks To examine the incidence, severity and frequency of adverse events (AEs), including serious adverse events (SAEs) during treatment with NNZ-2591.
Pharmacokinetic - Typical AUC24 of 30 kg Child 13 weeks Area under the concentration-time curve of NNZ-2591 over 24 hours
Pharmacokinetic - Typical t1/2 in 30 kg Child 13 weeks Apparent terminal elimination half-life of NNZ-2591
- Secondary Outcome Measures
Name Time Method ORCA 13 weeks Observer-Reported Communication Ability (ORCA) - Total Score. Range of Scores was (25.8-83.8) with higher scores begin better
CGI-I 13 weeks 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.
CIC 13 weeks Caregiver Impression of Improvement: Measured on a 7 point Likert scale (1-7) where lower scores are better.
CGI-S 13 weeks Phelan-McDermid syndrome-specific Clinical Global Impression Scale-Severity (CGI-S) -Overall Score based on a 7 point Likert scale (1-7) where a lower score is better.
Top 3 Concerns 13 weeks Caregiver Top 3 Concerns - Total Concerns Severity: Change from baseline. The range of scores was (0-30) for total concerns, with higher scores being worse
MB-CDI 13 weeks MacArthur-Bates Communicative Development Inventory (MB-CDI) - change from baseline. Range of scores was (0-792) with higher scores being better.
ABC-2 13 weeks Aberrant Behavior Checklist-2 (ABC-2) - Total score: Change from baseline. Range of scores was (0-174) with higher scores being worse
CSHQ 13 weeks Child Sleep Habits Questionnaire (CSHQ) - Total Score. Range of scores was (33-99) with higher scores being worse.
GIHQ 13 weeks Gastrointestinal Health Questionnaire (GIHQ) - Total Frequency Score: Change from Baseline. Range of scores was (0-212) with higher scores being worse.
VABS-3 13 weeks Vineland Adaptive Behavior Scales-3, Composite Standard Score. Range of scores was (20-140) with higher scores being better.
QI-Disability 13 weeks Quality of Life Inventory-Disability (QI-Disability) Overall Score - change from baseline. Range of scores was (0-100) with higher scores being better.
ICND 13 weeks Assessed by Impact of Childhood Neurological Disability (ICND)-Overall quality of life rating
PMS-DSRS 13 weeks PMS Clinician Domain Specific Rating Scale - Total Severity Score. Range of Scores Was (0-20) With Higher Scores Being Worse.
Behavior Problems Inventory - Short Form 13 weeks Total Frequency Score - Change from Baseline. Range of scores was (0-4) for each behavior, with lower scores being better.
Trial Locations
- 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