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Trial · Interventional

CompletedPhase 2Results postedRegistry data

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

Short name PMS-001

NCTNCT05025241 (opens ClinicalTrials.gov in a new tab)Other idNEU-2591-PMS-001
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 2
Enrollment
18 participants (actual)
Sponsor
Neuren Pharmaceuticals Limited · Industry
Design
Allocation not applicable · Open label (no masking)
Countries
1 country

United States

Start
8 Aug 2022
Primary completion
1 Nov 2023
Completion
17 Nov 2023
First posted
27 Aug 2021
Last update posted
3 Jun 2025
Conditions
Phelan-McDermid Syndrome

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
202220232024
  1. Ph 2

    PMS-001

    NCT05025241

    8 Aug 2022 to 17 Nov 2023

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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

Interventions

  • NNZ-2591Drug

Arms1

  • Experimental

    NNZ-2591

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

Primary outcomes3

Outcomes the sponsor listed as primary.

  1. Safety and Tolerability

    Time frame · 13 weeks

    Registry description

    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.

    Registry description

    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.

    Registry description

    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(14)

  1. CGI-I

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

    Registry description

    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

    Registry description

    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).

    Registry description

    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.

    Registry description

    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).

    Registry description

    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.

    Registry description

    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.

    Registry description

    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.

    Registry description

    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.

    Registry description

    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.

    Registry description

    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.

    Registry description

    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.

    Registry description

    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.

    Registry description

    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.

    Registry description

    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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeCount of participants· 13 weeks

Safety and Tolerability

GroupValue (Participants)
NNZ-259117
Primary outcomeMean· Pre-dose, 1-3 h post-dose and/or 4-7 h post-dose at Weeks 2, 6 and 13.

Pharmacokinetic - Mean AUC24

GroupValue (µg.h/mL)Spread
PK Population411116
Primary outcomeMean· Pre-dose, 1-3 h post-dose and/or 4-7 h post-dose at Weeks 2, 6 and 13.

Pharmacokinetic - t1/2

GroupValue (hours)Spread
PK Population8.022.33
Secondary and other outcome results(5)
Secondary outcomeMean· CGI-I was assessed at Weeks 6, 13/EOT & 15. Overall improvement scores relate to Week 13/EOT visit.

CGI-I

GroupValue (score on a scale)Spread
NNZ-25912.40.86
Secondary outcomeMean· CIC was assessed at Week13/EOT

CIC

GroupValue (score on a scale)Spread
NNZ-25912.71.02
Secondary outcomeMean· Change in score assessed from baseline (visit 3, week 0) to visit 16 (week 13/EOT).

CGI-S

GroupValue (score on a scale)Spread
NNZ-2591-0.40.5
Secondary outcomeMean· Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in overall improvement score.

Top 3 Concerns

GroupValue (score on a scale)Spread
NNZ-2591-5.95.86
Secondary outcomeMean· Change from baseline (visit 3, week 0) to visit 13/EOT (week 16).

MB-CDI

GroupValue (score on a scale)Spread
NNZ-259112.335.19

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
NNZ-2591All enrolled participants0 / 181 / 1817 / 18

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies1

Studies that cite this trial.

More studies

1 study on this page

PubMed tag: none · 2026

Corrected

NNZ-2591 in Children and Adolescents With Phelan-McDermid Syndrome: Single-Group, Open-Label, Phase 2 Trial Results.

Neumeyer et al. 2026Neurology. Geneticscited by 1

PMID 41450730PMC12735298DOI 10.1212/nxg.0000000000200338PUB-41450730

Free to read · publisher termsCC BY-NC-ND
Read at sourceRead the notice

Eligibility

Who could join, as posted.

Sex
All
Age
from 3 Years up to 12 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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

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