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

NCT05025241 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: NEU-2591-PMS-001
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 4

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.

Conditions

Phelan-McDermid Syndrome

Keywords

Phelan-McDermid Syndrome

Outcome Measures

Primary Outcomes (3)

• 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 - Mean AUC24

  Approximately nine sparse pharmacokinetic (PK) samples were collected from each participant under steady-state conditions. These samples were taken at pre-dose, 1-3 hours post-dose, and/or 4-7 hours post-dose during Weeks 2, 6, and 13. The individual pharmacokinetic parameters for NNZ-2591, including half-life (t1/2) and area under the curve over 24 hours (AUC24), were derived using subject-level concentration-time profiles from the study population model.

  Pre-dose, 1-3 h post-dose and/or 4-7 h post-dose at Weeks 2, 6 and 13.

• Pharmacokinetic - t1/2

  Approximately nine sparse pharmacokinetic (PK) samples were collected from each participant under steady-state conditions. These samples were taken at pre-dose, 1-3 hours post-dose, and/or 4-7 hours post-dose during Weeks 2, 6, and 13. The individual pharmacokinetic parameters for NNZ-2591, including half-life (t1/2) and area under the curve over 24 hours (AUC24), were derived using subject-level concentration-time profiles from the study population model.

  Pre-dose, 1-3 h post-dose and/or 4-7 h post-dose at Weeks 2, 6 and 13.

Secondary Outcomes (14)

• CGI-I

  CGI-I was assessed at Weeks 6, 13/EOT & 15. Overall improvement scores relate to Week 13/EOT visit.

• CIC

  CIC was assessed at Week13/EOT

• CGI-S

  Change in score assessed from baseline (visit 3, week 0) to visit 16 (week 13/EOT).

• Top 3 Concerns

  Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in overall improvement score.

• MB-CDI

  Change from baseline (visit 3, week 0) to visit 13/EOT (week 16).

Study Arms (1)

NNZ-2591

EXPERIMENTAL

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

Drug: NNZ-2591

Interventions

NNZ-2591 DRUG

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

Also known as: Cyclo-L-Glycyl-L-2-Allylproline

NNZ-2591

Eligibility Criteria

• Age: 3 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Neuren Pharmaceuticals Limited: lead

Study Sites (4)

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Neumeyer AM, Srivastava S, Holder JL, Milad MA, Squires L, Jones NE, Glass L, Berry-Kravis E. NNZ-2591 in Children and Adolescents With Phelan-McDermid Syndrome: Single-Group, Open-Label, Phase 2 Trial Results. Neurol Genet. 2025 Dec 23;12(1):e200338. doi: 10.1212/NXG.0000000000200338. eCollection 2026 Feb.

  PMID: 41450730 DERIVED

MeSH Terms

Conditions

Telomeric 22q13 Monosomy Syndrome

Interventions

cyclo-L-glycyl-L-2-allylproline

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Neuren Pharmaceuticals

MedicalInformation@neurenpharma.com

+61 (3) 9092 0480

Study Officials

• James Shaw

  Neuren Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2021
• First Posted: August 27, 2021
• Study Start: August 8, 2022
• Primary Completion: November 1, 2023
• Study Completion: November 17, 2023
• Last Updated: June 3, 2025
• Results First Posted: May 30, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)