Phelan-McDermid SyndromePhase 2PMS-001NCT05025241

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

A Phase 2 study testing NNZ-2591 in people with Phelan-McDermid Syndrome, run by Neuren Pharmaceuticals Limited at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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 more about this study

Who is it for?: Ages 3 to 12 years
Conditions the study is for: Phelan-McDermid Syndrome
What is being tested?: NNZ-2591
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 18 participants
Where: 4 sitesUnited States
Study dates: 8 Aug 2022to 17 Nov 2023
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 3 to 12 years
All sexes
No healthy volunteers
Child

Who may be able to join

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.

Who cannot join

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 .

Show all 21Show fewer

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

Trial locations and contacts

4 sites in 1 country.

United States4 sites

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

Other trials in United States

About this study

Official title: An Open-Label Study of the Safety, Tolerability, and Pharmacokinetics 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.

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: Phelan-McDermid Syndrome
Being tested: NNZ-2591
Keywords: Phelan-McDermid Syndrome
Medical subject headings: Telomeric 22q13 Monosomy Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT05025241
Study group	Role	What they receive
NNZ-2591	Experimental	NNZ-2591 oral solution (50mg/mL) to be administered twice daily dose for 13 weeks. Receives: Drug: NNZ-2591

What is being measured

The primary outcome is the main question the study is designed to answer.

Safety and Tolerability
To examine the incidence, severity and frequency of adverse events (AEs), including serious adverse events (SAEs) during treatment with NNZ-2591.
Measured: 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.
Measured: 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.
Measured: 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
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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total frequency score.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

8 Aug 202217 Nov 2023

First posted27 Aug 2021
Study start8 Aug 2022
Primary completion1 Nov 2023
Study completion17 Nov 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Phelan-McDermid SyndromeStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

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

IDs, dates and publications

ClinicalTrials.gov ID: NCT05025241
Sponsor's protocol ID: NEU-2591-PMS-001
Acronym: PMS-001
Status last verified: Jun 2025
First submitted: 24 Aug 2021
Last updated: 3 Jun 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 41450730

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 3
An Open-label Study of NNZ-2591 in Pediatric Participants With Phelan-McDermid Syndrome
Phelan-McDermid Syndrome
RecruitingPhase 3
A Study of NNZ-2591 in Pediatric Participants With Phelan-McDermid Syndrome
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Active, not recruiting
Web Intervention for Parents of Youth With Genetic Syndromes (WINGS)
Telomeric 22Q13 Monosomy Syndrome, Tuberous Sclerosis
RecruitingPhase 1/2
JAG201 Gene Therapy Study in Children & Adults With SHANK3 Haploinsufficiency
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Active, not recruitingObservational study
Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
Phelan-McDermid Syndrome, Autism Spectrum Disorder

All Phelan-McDermid Syndrome trials

Study at a glance

From the registry record, last updated by the sponsor on 3 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-Label Study of the Safety, Tolerability, and Pharmacokinetics of Oral NNZ-2591 in Phelan-McDermid Syndrome (PMS-001)
ClinicalTrials.gov ID: NCT05025241
Acronym / sponsor ID: PMS-001 / NEU-2591-PMS-001
Conditions: Phelan-McDermid Syndrome
Keywords: Phelan-McDermid Syndrome
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 18 participants (actual)
Lead sponsor: Neuren Pharmaceuticals LimitedIndustry (pharma, biotech, devices)
Study start: 8 Aug 2022 (actual)
Primary completion: 1 Nov 2023 (actual)
Study completion: 17 Nov 2023 (actual)
First posted: 27 Aug 2021 (actual)
Results: Posted 30 May 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

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

Who may qualify

Ages: 3 to 12 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (7 listed)

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

Key exclusion criteria (21 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
NNZ-2591Also: Cyclo-L-Glycyl-L-2-AllylprolineNNZ-2591 oral solution (50mg/mL) to be administered twice daily dose for 13 weeks.	Drug	NNZ-2591

Primary outcome

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.
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.
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.

14 secondary outcomes

CGI-I
Time frame: CGI-I was assessed at Weeks 6, 13/EOT & 15. Overall improvement scores relate to Week 13/EOT visit.
CIC
Time frame: CIC was assessed at Week13/EOT
CGI-S
Time frame: Change in score assessed from baseline (visit 3, week 0) to visit 16 (week 13/EOT).
Top 3 Concerns
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in overall improvement score.
MB-CDI
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16).
ORCA
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in Total Score.
ABC-2
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total score.
CSHQ
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total score.
GIHQ
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total frequency score.
VABS-3
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in composite standard score.
QL-Disability
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in overall score score.
ICND
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in overall quality of life rating score.
PMS-DSRS
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in overall severity score.
Behavior Problems Inventory - Short Form
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total frequency score.

Results and safety

Results posted to the registry on 30 May 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
NNZ-2591	23	18

Primary outcome: Safety and Tolerability

Time frame: 13 weeks. Count of participants. Unit: Participants

Measure	NNZ-2591 n = 18
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

Population analysed: Intention to treat population

Primary outcome: 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.. Mean (Standard Deviation). Unit: µg.h/mL

Measure	PK Population n = 18
Value	411 (116)

Population analysed: PK Population

Primary outcome: 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.. Mean (Standard Deviation). Unit: hours

Measure	PK Population n = 18
Value	8.02 (2.33)

Population analysed: All participants enrolled in this study who receive the study drug through to the morning dose of Week 2 (Visit 5) as a minimum, and who undergo PK sample collection at least one of the specified post-dose time point(s).

14 secondary outcomes are reported in the full results.

Adverse events

Time frame: 15 weeks for each participant starting on date of first dose. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
NNZ-2591	1 of 18 (5.6%)	17 of 18 (94.4%)	0 of 18

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 41450730Neumeyer 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.
Individual participant dataSharing planned: No

Related trials for Phelan-McDermid Syndrome

RecruitingPhase 3
An Open-label Study of NNZ-2591 in Pediatric Participants With Phelan-McDermid Syndrome
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

James Shaw study director

Neuren Pharmaceuticals

4 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing NNZ-2591 in people with Phelan-McDermid Syndrome, run by Neuren Pharmaceuticals Limited at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and Tolerability (time frame: 13 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05025241, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2025.