Clinical trial NCT05025241: An Open-Label Study of Oral NNZ-2591 in Phelan-McDermid Syndrome (PMS-001)
Official title: An Open-Label Study of the Safety, Tolerability, and Pharmacokinetics of Oral NNZ-2591 in Phelan-McDermid Syndrome (PMS-001)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Phelan-McDermid Syndrome
Keywords: Phelan-McDermid Syndrome
Lead sponsor: Neuren Pharmaceuticals Limited
Sponsor class: INDUSTRY
First posted: 2021-08-27
Enrollment: 18
Sex: ALL
Minimum age (years): 3
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety and Tolerability
timeFrame: 13 weeks
measure: Pharmacokinetic - Mean AUC24
timeFrame: Pre-dose, 1-3 h post-dose and/or 4-7 h post-dose at Weeks 2, 6 and 13.
measure: Pharmacokinetic - t1/2
timeFrame: Pre-dose, 1-3 h post-dose and/or 4-7 h post-dose at Weeks 2, 6 and 13.
Secondary outcomes:
measure: CGI-I
timeFrame: CGI-I was assessed at Weeks 6, 13/EOT & 15. Overall improvement scores relate to Week 13/EOT visit.
measure: CIC
timeFrame: CIC was assessed at Week13/EOT
measure: CGI-S
timeFrame: Change in score assessed from baseline (visit 3, week 0) to visit 16 (week 13/EOT).
measure: Top 3 Concerns
timeFrame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in overall improvement score.
measure: MB-CDI
timeFrame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16).
measure: ORCA
timeFrame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in Total Score.
measure: ABC-2
timeFrame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total score.
measure: CSHQ
timeFrame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total score.
measure: GIHQ
timeFrame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total frequency score.
measure: VABS-3
timeFrame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in composite standard score.
measure: QL-Disability
timeFrame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in overall score score.
measure: ICND
timeFrame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in overall quality of life rating score.
measure: PMS-DSRS
timeFrame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in overall severity score.
measure: Behavior Problems Inventory - Short Form
timeFrame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total frequency score.
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
Study officials:
affiliation: Neuren Pharmaceuticals
name: James Shaw
role: STUDY_DIRECTOR
References: