An Open-Label Study of Oral NNZ-2591 in Phelan-McDermid Syndrome (PMS-001)
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: NNZ-2591 NNZ-2591 oral solution (50mg/mL) to be administered twice daily dose for 13 weeks. |
Drug: NNZ-2591
NNZ-2591 oral solution (50mg/mL) to be administered twice daily dose for 13 weeks.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 - Measurement of Cmax [13 weeks]
Maximum observed concentration (Cmax) of NNZ-2591
- Pharmacokinetic - Measurement of AUC [13 weeks]
Area under the concentration-time curve of NNZ-2591
- Pharmacokinetic - Measurement of time to Cmax [13 weeks]
Time to Cmax of NNZ-2591
- Pharmacokinetic - Measurement of t1/2 [13 weeks]
Apparent terminal elimination half-life of NNZ-2591
Secondary Outcome Measures
- Exploratory efficacy measurement [13 weeks]
Assessed by Phelan-McDermid syndrome-specific Clinical Global Impression Scale-Overall Improvement (CGI-I)
- Exploratory efficacy measurement [13 weeks]
Assessed by Caregiver Impression of Improvement
- Exploratory efficacy measurement [13 weeks]
Assessed by Phelan-McDermid syndrome-specific Clinical Global Impression Scales-Domain Improvement
- Exploratory efficacy measurement [13 weeks]
Assessed by Phelan-McDermid syndrome-specific Clinical Global Impression Scale-Severity (CGI-S)-Overall and Domain
- Exploratory efficacy measurement [13 weeks]
Assessed by Caregiver Top 3 Concerns Likert Scale
- Exploratory efficacy measurement [13 weeks]
Assessed by MacArthur-Bates Communicative Development Inventory (MB-CDI)
- Exploratory efficacy measurement [13 weeks]
Assessed by Observer-Reported Communication Ability (ORCA)
- Exploratory efficacy measurement [13 weeks]
Assessed by Aberrant Behavior Checklist-2 (ABC-2)
- Exploratory efficacy measurement [13 weeks]
Assessed by Child Sleep Habits Questionnaire (CSHQ)
- Exploratory efficacy measurement [13 weeks]
Assessed by Gastrointestinal Health Questionnaire (GIHQ)
- Exploratory efficacy measurement [13 weeks]
Assessed by Vineland Adaptive Behavior Scales-3, Interview version
- Exploratory efficacy measurement [13 weeks]
Caregiver Diaries
- Exploratory efficacy measurement [13 weeks]
Assessed by Quality of Life Inventory-Disability (QI-Disability)
- Exploratory efficacy measurement [13 weeks]
Assessed by Impact of Childhood Neurological Disability (ICND)-Overall quality of life rating
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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.
Exclusion Criteria:
-
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.
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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.
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Actively undergoing regression or loss of skills.
-
Unstable seizure profile.
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Current clinically significant renal conditions and abnormalities
-
Current clinically significant cardiovascular, renal, hepatic, gastrointestinal, respiratory, endocrine disease, or clinically significant organ impairment.
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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.
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Has planned surgery during the study.
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History of, or current, cerebrovascular disease or brain trauma.
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History of, or current catatonia or catatonia-like symptoms.
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History of, or current, malignancy.
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Current major or persistent depressive disorder (including bipolar depression).
-
Significant, uncorrected visual or uncorrected hearing impairment.
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Allergy to strawberry.
-
Positive pregnancy test
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Rush University Medical Center | Chicago | Illinois | United States | 60612 |
| 2 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
| 3 | Boston Children's Hospital | Boston | Massachusetts | United States | 02115 |
| 4 | Texas Children's Hospital | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- Neuren Pharmaceuticals Limited
Investigators
- Study Director: James Shaw, Neuren Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NEU-2591-PMS-001