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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Phelan-McDermid 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 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
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: James Shaw; Phone Number: +61 427 299 669; Email: jshaw@neurenpharma.com

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 12 years (Child)
• Accepts Healthy Volunteers: No

Description

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

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 dose for 13 weeks.	Drug: NNZ-2591; NNZ-2591 oral solution (50mg/mL) to be administered twice daily dose 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 Caregiver Impression of Improvement	13 weeks
Exploratory efficacy measurement	Assessed by Caregiver Top 3 Concerns Likert Scale	13 weeks
Exploratory efficacy measurement	Assessed by MacArthur-Bates Communicative Development Inventory (MB-CDI)	13 weeks
Exploratory efficacy measurement	Assessed by Observer-Reported Communication Ability (ORCA)	13 weeks
Exploratory efficacy measurement	Assessed by Aberrant Behavior Checklist-2 (ABC-2)	13 weeks
Exploratory efficacy measurement	Assessed by Child Sleep Habits Questionnaire (CSHQ)	13 weeks
Exploratory efficacy measurement	Assessed by Gastrointestinal Health Questionnaire (GIHQ)	13 weeks
Exploratory efficacy measurement	Assessed by Vineland Adaptive Behavior Scales-3, Interview version	13 weeks
Exploratory efficacy measurement	Caregiver Diaries	13 weeks
Exploratory efficacy measurement	Assessed by Quality of Life Inventory-Disability (QI-Disability)	13 weeks
Exploratory efficacy measurement	Assessed by Impact of Childhood Neurological Disability (ICND)-Overall quality of life rating	13 weeks
Exploratory efficacy measurement	Assessed by Phelan-McDermid syndrome-specific Clinical Global Impression Scale-Overall Improvement (CGI-I)	13 weeks
Exploratory efficacy measurement	Assessed by Phelan-McDermid syndrome-specific Clinical Global Impression Scales-Domain Improvement	13 weeks
Exploratory efficacy measurement	Assessed by Phelan-McDermid syndrome-specific Clinical Global Impression Scale-Severity (CGI-S)-Overall and Domain	13 weeks

Collaborators and Investigators

• Sponsor: Neuren Pharmaceuticals Limited
• Investigators: Study Director: James Shaw, Neuren Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2022
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: August 24, 2021
• First Submitted That Met QC Criteria: August 24, 2021
• First Posted (Actual): August 27, 2021

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 10, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Phelan-McDermid Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Chromosome Aberrations; Aneuploidy; Monosomy; Syndrome; Chromosome Disorders; Chromosome Deletion
• Other Study ID Numbers: NEU-2591-PMS-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