Phelan-McDermid SyndromePhase 3NCT07281079
A Study of NNZ-2591 in Pediatric Participants With Phelan-McDermid Syndrome
A Phase 3 study testing NNZ-2591 in people with Phelan-McDermid Syndrome, run by Neuren Pharmaceuticals Limited at 18 sites in 2 countries.
Trial summary
This Phase 3, randomized, double-blind, parallel-group (2-arm), placebo-controlled, multicenter study will evaluate the efficacy and safety of NNZ-2591 compared to placebo in pediatric participants 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?
- Yes, some participants may receive a placebo
- How many people
- 160 participants
- Where
- 18 sitesin 2 countries
- Study dates
- 12 Nov 2025to 15 Nov 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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
- Male or female pediatric participants with Phelan-McDermid syndrome ages 3 to 12 years (inclusive) at the time of signing the informed consent.
- Clinical diagnosis of Phelan-McDermid syndrome with a documented disease-causing genetic abnormality of SHANK3.
- Body weight ≥ 10 kg at Screening.
- Participants with a PMSA-S overall score ≥ 3 at the Screening and Baseline visits.
- Not actively undergoing regression or loss of skills.
Who cannot join
- Use of exclusionary medication or unstable treatment regimens of acceptable concomitant medications as required by the protocol.
- Current treatment with more than 3 allowable psychotropic medications.
- Participants with seizures must be controlled on no more than 2 anticonvulsant medications (not counting rescue medications).
- Psychotropic medications or any other medication used for a chronic illness (not including antibiotics, pain relievers, anti-diarrheals, and laxatives) with doses and dosing regimen that have not been stable for at least 4 weeks before Screening. If the treatment was discontinued, the discontinuation must have occurred no fewer than 2 weeks before the start of Screening.
- Any intercurrent seizures in the past 6 months and /or more than 1 seizure in the past 12 months. •A single febrile seizure in the 6 months prior to screening is allowable if no rescue medication was required.
- Abnormal liver function laboratory results during the Screening period, as defined by the protocol
- Abnormal QT interval on Screening ECG as defined by the protocol.
Trial locations and contacts
18 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
18 sites in 2 countries
United States17 sites, 17 recruiting
- Recruiting
Neuren PMS-301 Site #117
Ann Arbor, Michigan, 48109
medicalinformation@neurenpharma.com, 231-203-8050, medicalinformation@neurenpharma.com
- Recruiting
Neuren PMS-301 Site #105
Atlanta, Georgia, 30322
medicalinformation@neurenpharma.com, 231-203-8050, medicalinformation@neurenpharma.com
- Recruiting
Neuren PMS-301 Site #116
Birmingham, Alabama, 35233
medicalinformation@neurenpharma.com, 231-203-8050, medicalinformation@neurenpharma.com
- Recruiting
Neuren PMS-301 Site#106
Brookline, Massachusetts, 02445
medicalinformation@neurenpharma.com, 231-203-8050, medicalinformation@neurenpharma.com
- Recruiting
Neuren PMS-301 Site #113
Charlottesville, Virginia, 22903
medicalinformation@neurenpharma.com, 231-203-8050, medicalinformation@neurenpharma.com
- Recruiting
Neuren PMS-301 Site#109
Chevy Chase, Maryland, 20815
medicalinformation@neurenpharma.com, 231-203-8050, medicalinformation@neurenpharma.com
- Recruiting
Neuren PMS-301 Site#102
Chicago, Illinois, 60612
medicalinformation@neurenpharma.com, 231-203-8050, medicalinformation@neurenpharma.com
- Recruiting
Neuren PMS-301 Site#108
Cincinnati, Ohio, 45229
medicalinformation@neurenpharma.com, 231-203-8050, medicalinformation@neurenpharma.com
- Recruiting
Neuren PMS-301 Site#110
Columbus, Ohio, 43205
medicalinformation@neurenpharma.com, 231-203-8050, medicalinformation@neurenpharma.com
- Recruiting
Neuren PMS-301 Site#122
Glendale, California, 91203
medicalinformation@neurenpharma.com, 231-203-8050, medicalinformation@neurenpharma.com
- Recruiting
Neuren PMS-301 Site#115
Houston, Texas, 77030
medicalinformation@neurenpharma.com, 231-203-8050, medicalinformation@neurenpharma.com
- Recruiting
Neuren PMS-301 Site#104
Lexington, Massachusetts, 02421
medicalinformation@neurenpharma.com, 231-203-8050, medicalinformation@neurenpharma.com
- Recruiting
Neuren PMS-301 Site#101
New York, New York, 10029
medicalinformation@neurenpharma.com, 231-203-8050, medicalinformation@neurenpharma.com
- Recruiting
Neuren PMS-301 Site #112
Palo Alto, California, 94305
medicalinformation@neurenpharma.com, 231-203-8050, medicalinformation@neurenpharma.com
- Recruiting
Neuren PMS-301 Site#103
San Diego, California, 92123
medicalinformation@neurenpharma.com, 231-203-8050, medicalinformation@neurenpharma.com
- Recruiting
Neuren PMS-301 Site#111
San Rafael, California, 94903
medicalinformation@neurenpharma.com, 231-203-8050, medicalinformation@neurenpharma.com
- Recruiting
Neuren PMS-301 Site #107
Washington D.C., District of Columbia, 20010
medicalinformation@neurenpharma.com, 231-203-8050, medicalinformation@neurenpharma.com
Canada1 site, 1 recruiting
- Recruiting
Neuren PMS-301 Site#201
Toronto, Ontario, M4G 1R8
medicalinformation@neurenpharma.com, 231-203-8050, medicalinformation@neurenpharma.com
About this study
Official title: A Phase 3 Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of Orally Administered NNZ-2591 Compared With Placebo in Pediatric Participants With Phelan-McDermid Syndrome
This Phase 3, randomized, double-blind, parallel-group (2-arm), placebo-controlled, multicenter study will evaluate the efficacy and safety of NNZ-2591 compared to placebo in pediatric participants with Phelan- McDermid Syndrome.
Read the detailed description
After providing informed consent/assent, pediatric participants with Phelan-McDermid syndrome ages 3-12 years of age will enter the 4-week Screening Period and undergo assessments for eligibility, baseline characteristics and symptom severity.
Once eligibility is confirmed, participants will be randomized in a 1:1 ratio to receive either orally administered NNZ-2591 or matching placebo during the 13-week Treatment Period. Subsequently, a 2-week safety follow-up period will occur immediately after the completion of the Treatment Period.
- Conditions
- Phelan-McDermid Syndrome
- Being tested
- NNZ-2591, Placebo
- Keywords
- Phelan McDermid Syndrome, NEU-2591-PMS-301, NNZ-2591, Neuren
- 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
The study drug will be administered twice daily orally.
PlaceboDrug
The study drug will be administered twice daily orally.
| Study group | Role | What they receive |
|---|---|---|
| NNZ-2591 Arm | Experimental | The total duration of this study for each participant will be up to approximately 17 to 19 weeks.
Participants will be randomized in a 1:1 ratio to receive orally administered NNZ-2591 during the 13-week Treatment Period. Receives: Drug: NNZ-2591 |
| Placebo Arm | Placebo comparator | The total duration of this study for each participant will be up to approximately 17 to 19 weeks.
Participants will be randomized in a 1:1 ratio to receive orally administered placebo matching NNZ-2591 during the 13-week Treatment Period. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of NNZ-2591 compared with placebo as measured by the Phelan-McDermid Syndrome Assessment of Change (PMSA-C) overall score.
Efficacy of NNZ-2591 compared with placebo as measured by the Phelan-McDermid Syndrome Assessment of Change (PMSA-C) overall score. The PMSA-C scores range from 1 to 7 with 1 indicating very much improved and 7 indicating very much worse.
Measured: Week 13
Efficacy of NNZ-2591 compared with placebo as measured by the change from baseline in the Vineland Adaptive Behavior Scales-3, Interview version (Vineland-3) receptive communication subdomain raw score.
Efficacy of NNZ-2591 compared with placebo as measured by the change from baseline in the Vineland Adaptive Behavior Scales-3, Interview version (Vineland-3) receptive communication subdomain raw score. A higher raw score for the receptive communication subdomain indicates better adaptive behavior.
Measured: Week 13
Secondary outcomes (6)
Efficacy of NNZ-2591 compared with placebo as measured by the Caregiver Impression of Change (CIC) overall score.
Efficacy of NNZ-2591 compared with placebo as measured by the Caregiver Impression of Change (CIC) overall score. The CIC scores range from 1 to 7 with 1 indicating very much improved and 7 indicating very much worse.
Measured: Week 13
Efficacy of NNZ-2591 compared with placebo as measured by the Phelan-McDermid Syndrome Assessment of Change (PMSA-C) domain scores.
Efficacy of NNZ-2591 compared with placebo as measured by the Phelan-McDermid Syndrome Assessment of Change (PMSA-C) domain scores. The PMSA-C domain scores range from 1 to 7 with 1 indicating very much improved and 7 indicating very much worse.
Measured: Week 13
Efficacy of NNZ-2591 compared with placebo as measured by the Caregiver Impression of Change (CIC) domain scores.
Efficacy of NNZ-2591 compared with placebo as measured by the Caregiver Impression of Change (CIC) domain scores. The CIC scores range from 1 to 7 with 1 indicating very much improved and 7 indicating very much worse.
Measured: Week 13
Efficacy of NNZ-2591 compared with placebo as measured by the change from baseline in Phelan-McDermid Syndrome Assessment of Severity (PMSA-S) domain scores.
Efficacy of NNZ-2591 compared with placebo as measured by the change from baseline in Phelan-McDermid Syndrome Assessment of Severity (PMSA-S) domain scores. The PMSA-S scores range from 1 to 7 with 1 indicating typical for age, not at all impaired and 7 among the most severely impaired.
Measured: Week 13
Efficacy of NNZ-2591 compared with placebo as measured by the change from baseline in PMSA-S overall score.
Efficacy of NNZ-2591 compared with placebo as measured by the change from baseline in PMSA-S overall score. The PMSA-S scores range from 1 to 7 with 1 indicating typical for age, not at all impaired and 7 among the most severely impaired.
Measured: Week 13
Efficacy of NNZ-2591 compared with placebo as measured by the change from baseline in PMS Clinician Domain Specific Rating Scale (PMS-DSRS) scores.
Efficacy of NNZ-2591 compared with placebo as measured by the change from baseline in PMS Clinician Domain Specific Rating Scale (PMS-DSRS) scores. The PMS-DSRS scores range from 0 to 4 with 0 indicating Symptom Not Present and 4 indicating Very Severe.
Measured: Week 13
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2025
- Study start12 Nov 2025
- Primary completion31 Oct 2027 (estimated)
- Study completion15 Nov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Phase 3, randomized, double-blind, parallel-group (2-arm), placebo-controlled, multicenter study
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Neuren Pharmaceuticals Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07281079
- Sponsor's protocol ID
- NEU-2591-PMS-301
- Status last verified
- Sep 2026
- First submitted
- 13 Nov 2025
- Last updated
- 28 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3 Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of Orally Administered NNZ-2591 Compared With Placebo in Pediatric Participants With Phelan-McDermid Syndrome
- ClinicalTrials.gov ID
- NCT07281079
- Acronym / sponsor ID
- NEU-2591-PMS-301
- Conditions
- Phelan-McDermid Syndrome
- Keywords
- Phelan McDermid Syndrome, NEU-2591-PMS-301, NNZ-2591, Neuren
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- Neuren Pharmaceuticals LimitedIndustry (pharma, biotech, devices)
- Study start
- 12 Nov 2025 (actual)
- Primary completion
- 31 Oct 2027 (estimated)
- Study completion
- 15 Nov 2027 (estimated)
- First posted
- 15 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This Phase 3, randomized, double-blind, parallel-group (2-arm), placebo-controlled, multicenter study will evaluate the efficacy and safety of NNZ-2591 compared to placebo in pediatric participants with Phelan- McDermid Syndrome.
Detailed description
After providing informed consent/assent, pediatric participants with Phelan-McDermid syndrome ages 3-12 years of age will enter the 4-week Screening Period and undergo assessments for eligibility, baseline characteristics and symptom severity.
Once eligibility is confirmed, participants will be randomized in a 1:1 ratio to receive either orally administered NNZ-2591 or matching placebo during the 13-week Treatment Period. Subsequently, a 2-week safety follow-up period will occur immediately after the completion of the Treatment Period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Phase 3, randomized, double-blind, parallel-group (2-arm), placebo-controlled, multicenter study
| Arm | Type | Receives |
|---|---|---|
| NNZ-2591 Arm | Experimental | Drug: NNZ-2591The total duration of this study for each participant will be up to approximately 17 to 19 weeks. Participants will be randomized in a 1:1 ratio to receive orally administered NNZ-2591 during the 13-week Treatment Period. |
| Placebo Arm | Placebo comparator | Drug: PlaceboThe total duration of this study for each participant will be up to approximately 17 to 19 weeks. Participants will be randomized in a 1:1 ratio to receive orally administered placebo matching NNZ-2591 during the 13-week Treatment Period. |
Who may qualify
- Ages
- 3 to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Male or female pediatric participants with Phelan-McDermid syndrome ages 3 to 12 years (inclusive) at the time of signing the informed consent.
- Clinical diagnosis of Phelan-McDermid syndrome with a documented disease-causing genetic abnormality of SHANK3.
- Body weight ≥ 10 kg at Screening.
- Participants with a PMSA-S overall score ≥ 3 at the Screening and Baseline visits.
- Not actively undergoing regression or loss of skills.
Key exclusion criteria (7 listed)
- Use of exclusionary medication or unstable treatment regimens of acceptable concomitant medications as required by the protocol.
- Current treatment with more than 3 allowable psychotropic medications.
- Participants with seizures must be controlled on no more than 2 anticonvulsant medications (not counting rescue medications).
- Psychotropic medications or any other medication used for a chronic illness (not including antibiotics, pain relievers, anti-diarrheals, and laxatives) with doses and dosing regimen that have not been stable for at least 4 weeks before Screening. If the treatment was discontinued, the discontinuation must have occurred no fewer than 2 weeks before the start of Screening.
- Any intercurrent seizures in the past 6 months and /or more than 1 seizure in the past 12 months. •A single febrile seizure in the 6 months prior to screening is allowable if no rescue medication was required.
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-2591The study drug will be administered twice daily orally. | Drug | NNZ-2591 Arm |
| PlaceboThe study drug will be administered twice daily orally. | Drug | Placebo Arm |
Primary outcome
Efficacy of NNZ-2591 compared with placebo as measured by the Phelan-McDermid Syndrome Assessment of Change (PMSA-C) overall score.
Time frame: Week 13
Efficacy of NNZ-2591 compared with placebo as measured by the Phelan-McDermid Syndrome Assessment of Change (PMSA-C) overall score. The PMSA-C scores range from 1 to 7 with 1 indicating very much improved and 7 indicating very much worse.
Efficacy of NNZ-2591 compared with placebo as measured by the change from baseline in the Vineland Adaptive Behavior Scales-3, Interview version (Vineland-3) receptive communication subdomain raw score.
Time frame: Week 13
Efficacy of NNZ-2591 compared with placebo as measured by the change from baseline in the Vineland Adaptive Behavior Scales-3, Interview version (Vineland-3) receptive communication subdomain raw score. A higher raw score for the receptive communication subdomain indicates better adaptive behavior.
6 secondary outcomes
Efficacy of NNZ-2591 compared with placebo as measured by the Caregiver Impression of Change (CIC) overall score.
Time frame: Week 13
Efficacy of NNZ-2591 compared with placebo as measured by the Phelan-McDermid Syndrome Assessment of Change (PMSA-C) domain scores.
Time frame: Week 13
Efficacy of NNZ-2591 compared with placebo as measured by the Caregiver Impression of Change (CIC) domain scores.
Time frame: Week 13
Efficacy of NNZ-2591 compared with placebo as measured by the change from baseline in Phelan-McDermid Syndrome Assessment of Severity (PMSA-S) domain scores.
Time frame: Week 13
Efficacy of NNZ-2591 compared with placebo as measured by the change from baseline in PMSA-S overall score.
Time frame: Week 13
Efficacy of NNZ-2591 compared with placebo as measured by the change from baseline in PMS Clinician Domain Specific Rating Scale (PMS-DSRS) scores.
Time frame: Week 13
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2026.
- 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
Phelan-McDermid Syndrome
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
SHANK3 Haploinsufficiency, Phelan-McDermid Syndrome
Active, not recruitingObservational study
Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
Phelan-McDermid Syndrome, Autism Spectrum Disorder
Active, not recruitingPhase 1
RB001 Gene Therapy Study in Children With SHANK3-related Phelan-McDermid Syndrome (PMS)
Phelan-McDermid Syndrome, SHANK3 Haploinsufficiency
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.
18 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing NNZ-2591 in people with Phelan-McDermid Syndrome, run by Neuren Pharmaceuticals Limited at 18 sites in 2 countries.
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 5 inclusion and 7 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: looking for participants now, as of the sponsor's last update on 28 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States, Canada. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Medical Information Lead (231-203-8050, medicalinformation@neurenpharma.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy of NNZ-2591 compared with placebo as measured by the Phelan-McDermid Syndrome Assessment of Change (PMSA-C) overall score. (time frame: Week 13). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Sep 2026.