Skip to main content
OpenTrials
Completed

NCT Number: NCT05025241

An Open-Label Study 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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Phelan-McDermid Syndrome Telomeric 22q13 Monosomy Syndrome

Age range

3 year–12 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Rush University Medical Center, Chicago, Illinois, United States

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.
  • 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.
  • History of, or current, malignancy.
  • Current major or persistent depressive disorder (including bipolar depression).
  • Significant, uncorrected visual or uncorrected hearing impairment.
  • Allergy to strawberry.
  • Positive pregnancy test
  • Subject is judged by the Investigator or Medical Monitor to be inappropriate for the study

Treatment and study plan

NNZ-2591

Drug

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

Other names: Cyclo-L-Glycyl-L-2-Allylproline

Primary outcomes

  1. Safety and Tolerability

    Time frame: 13 weeks

    To examine the incidence, severity and frequency of adverse events (AEs), including serious adverse events (SAEs) during treatment with NNZ-2591.

  2. Pharmacokinetic - Mean AUC24

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

    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.

  3. Pharmacokinetic - t1/2

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

    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.

Secondary outcomes

  1. CGI-I

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

    Phelan-McDermid Syndrome-specific Clinical Global Impression of Improvement Scale (CGI-I) - Overall Improvement Score on a 7 point Likert scale (1-7) where lower scores are better.

  2. CIC

    Time frame: CIC was assessed at Week13/EOT

    Caregiver Impression of Improvement: Measured on a 7 point Likert scale (1-7) where lower scores are better.

  3. CGI-S

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

    Phelan-McDermid syndrome-specific Clinical Global Impression Scale-Severity (CGI-S) -Change from baseline on Overall Score. Based on a 7 point Likert scale (1-7) where a lower score is better.

  4. Top 3 Concerns

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

    Caregiver Top 3 Concerns - Total Concerns Severity: Change from baseline. The range of scores was (0-30) for total concerns, with higher scores being worse

  5. MB-CDI

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

    MacArthur-Bates Communicative Development Inventory (MB-CDI) - change from baseline. Range of scores was (0-792) with higher scores being better.

  6. ORCA

    Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in Total Score.

    Observer-Reported Communication Ability (ORCA) - Change from baseline in Total Score. Range of Scores was (25.8-83.8) with higher scores being better

  7. ABC-2

    Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total score.

    Aberrant Behavior Checklist-2 (ABC-2) - Total score: Change from baseline. Range of scores was (0-174) with higher scores being worse

  8. CSHQ

    Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total score.

    Child Sleep Habits Questionnaire (CSHQ) - Change from baseline in Total Score. Range of scores was (33-99) with higher scores being worse.

  9. GIHQ

    Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total frequency score.

    Gastrointestinal Health Questionnaire (GIHQ) - Total Frequency Score: Change from Baseline. Range of scores was (0-212) with higher scores being worse.

  10. VABS-3

    Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in composite standard score.

    Vineland Adaptive Behavior Scales-3, Change from baseline in Composite Standard Score. Range of scores was (20-140) with higher scores being better.

  11. QL-Disability

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

    Quality of Life Inventory-Disability (QL-Disability) Overall Score - change from baseline. Range of scores was (0-100) with higher scores being better.

  12. ICND

    Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in overall quality of life rating score.

    Impact of Childhood Neurological Disability (ICND) - Change from baseline in overall quality of life rating. Range of (1- 6) for quality of life rating, with higher scores indicating greater impact.

  13. PMS-DSRS

    Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in overall severity score.

    PMS Clinician Domain Specific Rating Scale - Change from baseline in overall severity score. Range of Scores Was (0-20) With Higher Scores Being Worse.

  14. Behavior Problems Inventory - Short Form

    Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total frequency score.

    Total Frequency Score - Change from Baseline. Range of scores was (0-4) for each of 30 behaviors, total range (0-120), with lower scores being better.

Sponsors and collaborators

Lead sponsor

Neuren Pharmaceuticals Limited

Industry

Registry information

Official study title

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

Acronym: PMS-001

Important dates

Study start
2022
Primary completion
2023
Study completion
2023
First posted
Aug 27, 2021
Registry last updated
Jun 3, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.