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

Phelan-McDermid Syndrome Clinical Trial

— PMS-001  

Official title:

An Open-Label Study of the Safety, Tolerability, and Pharmacokinetics of Oral NNZ-2591 in Phelan-McDermid Syndrome (PMS-001)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05025241
• Other study ID #: NEU-2591-PMS-001
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 8, 2022
• Est. completion date: December 31, 2023

Study information

• Verified date: August 2023
• Source: Neuren Pharmaceuticals Limited
• Contact: n/a
• 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 Phelan-McDermid 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 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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 20
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 12 Years

Eligibility

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

Related Conditions & MeSH terms

• Chromosome Deletion
• Chromosome Disorders
• Phelan-McDermid Syndrome
• Syndrome

Intervention

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

Locations

Country	Name	City	State
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Rush University Medical Center	Chicago	Illinois
United States	Texas Children's Hospital	Houston	Texas

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 Phelan-McDermid syndrome-specific Clinical Global Impression Scale-Overall Improvement (CGI-I)	13 weeks
Secondary	Exploratory efficacy measurement	Assessed by Caregiver Impression of Improvement	13 weeks
Secondary	Exploratory efficacy measurement	Assessed by Phelan-McDermid syndrome-specific Clinical Global Impression Scales-Domain Improvement	13 weeks
Secondary	Exploratory efficacy measurement	Assessed by Phelan-McDermid syndrome-specific Clinical Global Impression Scale-Severity (CGI-S)-Overall and Domain	13 weeks
Secondary	Exploratory efficacy measurement	Assessed by Caregiver Top 3 Concerns Likert Scale	13 weeks
Secondary	Exploratory efficacy measurement	Assessed by MacArthur-Bates Communicative Development Inventory (MB-CDI)	13 weeks
Secondary	Exploratory efficacy measurement	Assessed by Observer-Reported Communication Ability (ORCA)	13 weeks
Secondary	Exploratory efficacy measurement	Assessed by Aberrant Behavior Checklist-2 (ABC-2)	13 weeks
Secondary	Exploratory efficacy measurement	Assessed by Child Sleep Habits Questionnaire (CSHQ)	13 weeks
Secondary	Exploratory efficacy measurement	Assessed by Gastrointestinal Health Questionnaire (GIHQ)	13 weeks
Secondary	Exploratory efficacy measurement	Assessed by Vineland Adaptive Behavior Scales-3, Interview version	13 weeks
Secondary	Exploratory efficacy measurement	Caregiver Diaries	13 weeks
Secondary	Exploratory efficacy measurement	Assessed by Quality of Life Inventory-Disability (QI-Disability)	13 weeks
Secondary	Exploratory efficacy measurement	Assessed by Impact of Childhood Neurological Disability (ICND)-Overall quality of life rating	13 weeks