An Open-label Study of NNZ-2591 in Pediatric Participants With Phelan-McDermid Syndrome

A Phase 3 Open-label Extension Study to Investigate the Long-term Safety and Efficacy of Orally Administered NNZ-2591 in Pediatric Participants With Phelan-McDermid Syndrome

This Phase 3, open-label extension, multicenter study will evaluate long-term safety, tolerability and efficacy of NNZ-2591 in pediatric participants with Phelan- McDermid Syndrome.

Study Overview

• Status: Recruiting
• Conditions: Phelan-McDermid Syndrome
• Intervention / Treatment: Drug: NNZ-2591

Detailed Description

After providing informed consent/assent, pediatric participants with Phelan-McDermid syndrome who participated in previous studies (NEU-2591-PMS-301 and NEU-2591-PMS-001) will undergo assessments for eligibility, baseline characteristics and symptom severity. Once eligibility is confirmed, participants will receive orally administered NNZ-2591 during the 52-week Treatment Period. A 2-week safety follow-up period will occur immediately after the completion of the Treatment Period.

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Medical Information Lead; Phone Number: 231-203-8050; Email: medicalinformation@neurenpharma.com

Study Locations

• United States
  • California
    • San Rafael, California, United States, 94903
      • Recruiting
      • Neuren PMS-302 Site#111
      • Contact: medicalinformation@neurenpharma.com; Phone Number: 2312038050; Email: medicalinformation@neurenpharma.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female pediatric participants with Phelan-McDermid syndrome ages 3 to 12 years (inclusive) at the time of signing the informed consent for the antecedent study.
2. Participant must have completed all applicable study visits for the antecedent study in which they participated.
3. Body weight ≥ 10 kg at Screening/Baseline.
4. Participants with a PMSA-S overall score ≥ 3 at the Screening and Baseline visits.
5. Not actively undergoing regression or loss of skills.

Exclusion Criteria:

1. Use of exclusionary medication or unstable treatment regimens of acceptable concomitant medications as required by the protocol.
2. Participants with seizures must be controlled on no more than 2 anticonvulsant medications (not counting rescue medications).
3. 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.
4. 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.
5. Abnormal liver function laboratory results during the Screening period, as defined by the protocol
6. Abnormal QT interval on Screening ECG as defined by the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NNZ-2591 Arm; The total duration of this study for each participant will be up to up to 56 weeks.	Drug: NNZ-2591; The study drug will be administered twice daily orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long-term safety and tolerability of NNZ-2591 as assessed by the incidence of adverse events across participants	Incidence of TEAEs, AESI and SAEs across participants	Baseline through Safety Follow-Up (Month 12)
Long-term safety and tolerability of NNZ-2591 as assessed by changes from Baseline assessments of ECG parameters events across participants.	Change from Baseline in ECG Heart Rate (bpm)	Baseline through Month 12
Long-term safety and tolerability of NNZ-2591 as assessed by changes from Baseline assessments of ECG parameters events across participants.	Change from Baseline PR Interval (ms QRS interval (ms)	Baseline through Safety Follow-Up (Month 12)
Long-term safety and tolerability of NNZ-2591 as assessed by changes from Baseline assessments of ECG parameters events across participants.	Change from Baseline in QT interval (ms)	Baseline through Safety Follow-Up (Month 12)
Long-term safety and tolerability of NNZ-2591 as assessed by changes from Baseline assessments of ECG parameters events across participants.	Change from Baseline in QTcB interval (ms)	Baseline through Safety Follow-Up (Month 12)
Long-term safety and tolerability of NNZ-2591 as assessed by changes from Baseline assessments of ECG parameters events across participants.	Change from Baseline in QTcF interval (ms)	Baseline through Safety Follow-Up (Month 12)
Long-term safety and tolerability of NNZ-2591 as assessed by changes from Baseline assessments of ECG parameters events across participants.	Change from Baseline in RR interval (ms)	Baseline through Safety Follow-Up (Month 12)
Long-term safety and tolerability of NNZ-2591 as assessed by changes from Baseline assessments of vital sign parameters events across participants.	Change from Baseline for heart rate (bpm)	Baseline through Month 12
Long-term safety and tolerability of NNZ-2591 as assessed by changes from Baseline assessments of vital sign parameters events across participants.	Change from Baseline for respiration rate (breaths per minute)	Baseline through Month 12
Long-term safety and tolerability of NNZ-2591 as assessed by changes from Baseline assessments of vital sign parameters events across participants.	Change from Baseline for Temperature (Celsius)	Baseline through Month 12
Long-term safety and tolerability of NNZ-2591 as assessed by changes from Baseline assessments of vital sign parameters events across participants.	Change from Baseline for Diastolic Blood Pressure (mm Hg)	Baseline through Month 12
Long-term safety and tolerability of NNZ-2591 as assessed by changes from Baseline assessments of vital sign parameters events across participants.	Change from Baseline for Systolic Blood Pressure (mm Hg)	Baseline through Month 12
Long-term safety and tolerability of NNZ-2591 as incidence of abnormal, clinically significant clinical laboratory parameters events across participants.	Incidence of abnormal and clinically significant laboratory parameters	Baseline through Month 12
Long-term safety and tolerability of NNZ-2591 as incidence of abnormal, clinically significant physical examination findings across participants.	Incidence of abnormal, clinically significant physical examination findings	Baseline through Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of NNZ-2591 as measured by the Phelan-McDermid Syndrome Assessment of Change (PMSA-C) overall score	Efficacy of NNZ-2591 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.	Months 3 and 12
Efficacy of NNZ-2591 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 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.	Months 3 and 12
Efficacy of NNZ-2591 as measured by the Phelan-McDermid Syndrome Assessment of Change (PMSA-C) domain scores.	Efficacy of NNZ-2591 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.	Months 3 and 12
Efficacy of NNZ-2591 as measured by the Caregiver Impression of Change (CIC) domain scores.	Efficacy of NNZ-2591 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.	Months 3 and 12
Efficacy of NNZ-2591 as measured by the change from baseline in Phelan-McDermid Syndrome Assessment of Severity (PMSA-S) domain scores.	Efficacy of NNZ-2591 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.	Months 3 and 12
Efficacy of NNZ-2591 as measured by the change from baseline in Phelan-McDermid Syndrome Assessment of Severity (PMSA-S) overall score.	Efficacy of NNZ-2591 as measured by the change from baseline in Phelan-McDermid Syndrome Assessment of Severity (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.	Months 3 and 12
Efficacy of NNZ-2591 as measured by the change from baseline in PMS Clinician Domain Specific Rating Scale (PMS-DSRS) scores.	Efficacy of NNZ-2591 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.	Months 3 and 12

Collaborators and Investigators

• Sponsor: Neuren Pharmaceuticals Limited

Study record dates

Study Major Dates

• Study Start (Estimated): May 20, 2026
• Primary Completion (Estimated): October 29, 2028
• Study Completion (Estimated): November 12, 2028

Study Registration Dates

• First Submitted: March 24, 2026
• First Submitted That Met QC Criteria: May 13, 2026
• First Posted (Actual): May 18, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Phelan McDermid Syndrome; NEU-2591-PMS-301; NNZ-2591; Neuren
• Additional Relevant MeSH Terms: Telomeric 22q13 Monosomy Syndrome; cyclo-L-glycyl-L-2-allylproline
• Other Study ID Numbers: NEU-2591-PMS-302

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No