CompletedNCT05025241PMS-001Updated Jun 3, 2025Results posted

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

A Phase 2 interventional study of NNZ-2591 in Phelan-McDermid Syndrome, sponsored by Neuren Pharmaceuticals Limited. Completed at 4 sites in United States. Open to participants aged 3 Years to 12 Years. Per ClinicalTrials.gov, last updated 2025-06-03.

Sponsored by Neuren Pharmaceuticals Limited · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 18
Allocation: Not applicable
Ages: 3 Years to 12 Years
Sex: All

Study summary

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

Read the 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.

Conditions studied

Phelan-McDermid Syndrome

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Keywords

Phelan-McDermid Syndrome

In context

Chromosome Disorders

54 studies on the registry are indexed under Chromosome Disorders; 7 are open to participants now.

This study's enrollment of 18 is below the median of 54 across 20 interventional studies indexed under Chromosome Disorders.

Browse Chromosome Disorders studies →

Lead sponsor

Neuren Pharmaceuticals Limited is the lead sponsor of 15 studies on the registry; 2 are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 3 Years to 12 Years
Sexes eligible: All
Accepts healthy volunteers: No

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

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

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 18 participants (actual)

Study arms

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

Interventions

DrugNNZ-2591
NNZ-2591 oral solution (50mg/mL) to be administered twice daily dose for 13 weeks.
Also known as: Cyclo-L-Glycyl-L-2-Allylproline

What researchers measure

Primary outcomes

Safety and Tolerability
To examine the incidence, severity and frequency of adverse events (AEs), including serious adverse events (SAEs) during treatment with NNZ-2591.
Time frame: 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.
Time frame: 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.
Time frame: Pre-dose, 1-3 h post-dose and/or 4-7 h post-dose at Weeks 2, 6 and 13.

Secondary outcomes

CGI-I
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.
Time frame: CGI-I was assessed at Weeks 6, 13/EOT & 15. Overall improvement scores relate to Week 13/EOT visit.
CIC
Caregiver Impression of Improvement: Measured on a 7 point Likert scale (1-7) where lower scores are better.
Time frame: CIC was assessed at Week13/EOT
CGI-S
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.
Time frame: Change in score assessed from baseline (visit 3, week 0) to visit 16 (week 13/EOT).
Top 3 Concerns
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
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in overall improvement score.
MB-CDI
MacArthur-Bates Communicative Development Inventory (MB-CDI) - change from baseline. Range of scores was (0-792) with higher scores being better.
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16).
ORCA
Observer-Reported Communication Ability (ORCA) - Change from baseline in Total Score. Range of Scores was (25.8-83.8) with higher scores being better
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in Total Score.
ABC-2
Aberrant Behavior Checklist-2 (ABC-2) - Total score: Change from baseline. Range of scores was (0-174) with higher scores being worse
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total score.
CSHQ
Child Sleep Habits Questionnaire (CSHQ) - Change from baseline in Total Score. Range of scores was (33-99) with higher scores being worse.
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total score.
GIHQ
Gastrointestinal Health Questionnaire (GIHQ) - Total Frequency Score: Change from Baseline. Range of scores was (0-212) with higher scores being worse.
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total frequency score.
VABS-3
Vineland Adaptive Behavior Scales-3, Change from baseline in Composite Standard Score. Range of scores was (20-140) with higher scores being better.
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in composite standard score.
QL-Disability
Quality of Life Inventory-Disability (QL-Disability) Overall Score - change from baseline. Range of scores was (0-100) with higher scores being better.
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in overall score score.
ICND
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.
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in overall quality of life rating score.
PMS-DSRS
PMS Clinician Domain Specific Rating Scale - Change from baseline in overall severity score. Range of Scores Was (0-20) With Higher Scores Being Worse.
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in overall severity score.
Behavior Problems Inventory - Short Form
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.
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total frequency score.

Results

Posted May 30, 2025

Participant flow

Participants were recruited based on physician referral at 4 academic medical centers between August 2022 and June 2023. The first participant entered screening on 08 August 2022, and the last participant entered screening on 22 June 2023. Of 23 consented participants, 18 met eligibility criteria and were enrolled into the study. Enrolled participants received NNZ2591 12 mg/kg by liquid oral dose twice daily

Screening

Participant flow — Screening
Milestone	NNZ-2591
Started	23
Completed	18
Not completed	5
Withdrew: Failed screening	5

Treatment and Follow Up

Participant flow — Treatment and Follow Up
Milestone	NNZ-2591
Started	18
Completed	15
Not completed	3
Withdrew: Adverse event	3

Outcome measures

PrimarySafety and Tolerability

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

Time frame:: 13 weeks
Reported as:: Count of participants · Participants

Safety and Tolerability
Participants	NNZ-2591
Participants with any AE	17
Participants with TEAE	17
Participants with Serious TEAE	1
Participants who discontinued due to TEAE	3
Participants with mild TEAE	11
Participants with moderate TEAE	5
Participants with severe TEAE	1

PrimaryPharmacokinetic - 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.

Time frame:: Pre-dose, 1-3 h post-dose and/or 4-7 h post-dose at Weeks 2, 6 and 13.
Reported as:: Mean · µg.h/mL

Pharmacokinetic - Mean AUC24
µg.h/mL	PK Population
Pharmacokinetic - Mean AUC24	411 ± 116

PrimaryPharmacokinetic - t1/2

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

Pharmacokinetic - t1/2
hours	PK Population
Pharmacokinetic - t1/2	8.02 ± 2.33

SecondaryCGI-I

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.

Time frame:: CGI-I was assessed at Weeks 6, 13/EOT & 15. Overall improvement scores relate to Week 13/EOT visit.
Reported as:: Mean · score on a scale

CGI-I
score on a scale	NNZ-2591
CGI-I	2.4 ± 0.86

Statistical analysis

NNZ-2591 · Wilcoxon Signed rank · p = <0.0001

SecondaryCIC

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

Time frame:: CIC was assessed at Week13/EOT
Reported as:: Mean · score on a scale

CIC
score on a scale	NNZ-2591
CIC	2.7 ± 1.02

Statistical analysis

NNZ-2591 · Wilcoxon Signed rank · p = 0.0003

SecondaryCGI-S

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.

Time frame:: Change in score assessed from baseline (visit 3, week 0) to visit 16 (week 13/EOT).
Reported as:: Mean · score on a scale

CGI-S
score on a scale	NNZ-2591
CGI-S	-0.4 ± 0.5

Statistical analysis

NNZ-2591 · Wilcoxon Signed rank · p = 0.0156

SecondaryTop 3 Concerns

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

Time frame:: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in overall improvement score.
Reported as:: Mean · score on a scale

Top 3 Concerns
score on a scale	NNZ-2591
Top 3 Concerns	-5.9 ± 5.86

Statistical analysis

NNZ-2591 · Wilcoxon Signed rank · p = 0.0005

SecondaryMB-CDI

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

Time frame:: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16).
Reported as:: Mean · score on a scale

MB-CDI
score on a scale	NNZ-2591
MB-CDI	12.3 ± 35.19

Statistical analysis

NNZ-2591 · Wilcoxon Signed rank · p = 0.0647

SecondaryORCA

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

Time frame:: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in Total Score.
Reported as:: Mean · score on a scale

ORCA
score on a scale	NNZ-2591
ORCA	1.9 ± 4.22

Statistical analysis

NNZ-2591 · Wilcoxon Signed rank · p = 0.0984

SecondaryABC-2

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

Time frame:: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total score.
Reported as:: Mean · score on a scale

ABC-2
score on a scale	NNZ-2591
ABC-2	-17.2 ± 19.65

Statistical analysis

NNZ-2591 · Wilcoxon Signed rank · p = 0.0013

SecondaryCSHQ

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

Time frame:: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total score.
Reported as:: Mean · score on a scale

CSHQ
score on a scale	NNZ-2591
CSHQ	-3.6 ± 5.68

Statistical analysis

NNZ-2591 · Wilcoxon Signed rank · p = 0.0191

SecondaryGIHQ

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

Time frame:: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total frequency score.
Reported as:: Mean · score on a scale

GIHQ
score on a scale	NNZ-2591
GIHQ	-9.6 ± 10.8

Statistical analysis

NNZ-2591 · Wilcoxon Signed rank · p = 0.0013

SecondaryVABS-3

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

Time frame:: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in composite standard score.
Reported as:: Mean · score on a scale

VABS-3
score on a scale	NNZ-2591
VABS-3	2.8 ± 7.82

Statistical analysis

NNZ-2591 · Wilcoxon Signed rank · p = 0.1710

SecondaryQL-Disability

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

Time frame:: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in overall score score.
Reported as:: Mean · score on a scale

QL-Disability
score on a scale	NNZ-2591
QL-Disability	6.1 ± 8.91

Statistical analysis

NNZ-2591 · Wilcoxon Signed rank · p = 0.0066

SecondaryICND

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.

Time frame:: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in overall quality of life rating score.
Reported as:: Mean · score on a scale

ICND
score on a scale	NNZ-2591
ICND	0.3 ± 0.69

Statistical analysis

NNZ-2591 · Wilcoxon Signed rank · p = 0.1094

SecondaryPMS-DSRS

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

Time frame:: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in overall severity score.
Reported as:: Mean · score on a scale

PMS-DSRS
score on a scale	NNZ-2591
PMS-DSRS	-0.9 ± 1.69

Statistical analysis

NNZ-2591 · Wilcoxon Signed rank · p = 0.0156

SecondaryBehavior Problems Inventory - Short Form

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.

Time frame:: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total frequency score.
Reported as:: Mean · score on a scale

Behavior Problems Inventory - Short Form
score on a scale	NNZ-2591
Behavior Problems Inventory - Short Form	-5.1 ± 9.41

Statistical analysis

NNZ-2591 · Wilcoxon Signed rank · p = 0.0326

Adverse events

Collected over 15 weeks for each participant starting on date of first dose. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
NNZ-2591	0/18 (0%)	1/18 (5.6%)	17/18 (94.4%)

Most frequent serious events

Most frequent serious events
Event	NNZ-2591
GastroenteritisGastrointestinal disorders	1/18

Most frequent other events

Showing 10 of 15

Most frequent other events
Event	NNZ-2591
Psychomotor HyperactivityNervous system disorders	4/18
PyrexiaGeneral disorders	3/18
Covid 19Infections and infestations	3/18
Decreased appetiteMetabolism and nutrition disorders	3/18
SomnolenceNervous system disorders	3/18
ConstipationGastrointestinal disorders	2/18
DiarrheaGastrointestinal disorders	2/18
NauseaGastrointestinal disorders	2/18
VomitingGastrointestinal disorders	2/18
FatigueGeneral disorders	2/18

Baseline characteristics

Intention to treat

Age, Continuous
Age, Continuous(years)	NNZ-2591
Mean	8.6 ± 2.7

Sex: Female, Male
Sex: Female, Male(Participants)	NNZ-2591
Female	6
Male	12

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	NNZ-2591
Race : White	16
Race : Black or African American	1
Race : Asian	0
Race : Native Hawaiian or other Pacific Islander	0
Race : American Indian or Alaska Native	0
Race : Multi Racial	1
Race : Other	0
Ethnicity : Hispanic or Latino	3
Ethnicity : Not Hispanic or Latino	15

Height (cm)
Height (cm)(cm)	NNZ-2591
Mean	130.6 ± 15.15

Weight (kg)
Weight (kg)(kg)	NNZ-2591
Mean	30.4 ± 10.75

BMI (kg/m^2)
BMI (kg/m^2)(kg/m^2)	NNZ-2591
Mean	17.4 ± 3.48

PMS Genotype
PMS Genotype(Participants)	NNZ-2591
Terminal Deletion - Class I	7
Terminal Deletion - Class II	3
Ring 22	0
Unbalanced Translocation	0
Interstitial Deletion	1
SHANK 3 variant/mutation	6
Other	1

History of regression
History of regression(Participants)	NNZ-2591
Yes	11
No	7

7 further baseline measures are reported on the registry.

Study locations

4 sites

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

References and documents

Study documents

Study protocol · Oct 30, 2023
Statistical analysis plan · Nov 6, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jun 3, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT05025241
Lead sponsor: Neuren Pharmaceuticals Limited
Responsible party: Sponsor
First posted: Aug 27, 2021
Start date: Aug 8, 2022
Primary completion: Nov 1, 2023
Completion: Nov 17, 2023
Results posted: May 30, 2025
Last update: Jun 3, 2025

Study contacts

James Shaw

study director · Neuren Pharmaceuticals

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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

Study summary

Conditions studied

Browse trials for

Keywords

In context

Chromosome Disorders

Lead sponsor

Who can participate

✓Inclusion criteria

✕Exclusion criteria

Study design

Study arms

Interventions

What researchers measure

Primary outcomes

Secondary outcomes

Results

Participant flow

Outcome measures

Adverse events

Baseline characteristics

Study locations

References and documents

Study documents

Individual participant data

Updates

Registry details

Key details

Study contacts

Oversight

Not currently enrolling

Follow this study

Discussion

Other studies in this condition

Other studies from this sponsor

Inclusion criteria

Exclusion criteria