A Study of NNZ-2591 in Pediatric Participants With Phelan-McDermid Syndrome

NCT07281079 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: NEU-2591-PMS-301
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Phelan-McDermid Syndrome

Keywords

Phelan McDermid Syndrome; NEU-2591-PMS-301; NNZ-2591; Neuren

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Week 13

Secondary Outcomes (6)

• Efficacy of NNZ-2591 compared with placebo as measured by the Caregiver Impression of Change (CIC) overall score.

  Week 13

• Efficacy of NNZ-2591 compared with placebo as measured by the Phelan-McDermid Syndrome Assessment of Change (PMSA-C) domain scores.

  Week 13

• Efficacy of NNZ-2591 compared with placebo as measured by the Caregiver Impression of Change (CIC) domain scores.

  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.

  Week 13

• Efficacy of NNZ-2591 compared with placebo as measured by the change from baseline in PMSA-S overall score.

  Week 13

Study Arms (2)

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.

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.

Drug: Placebo

Interventions

NNZ-2591 DRUG

The study drug will be administered twice daily orally.

NNZ-2591 Arm

Placebo DRUG

The study drug will be administered twice daily orally.

Placebo Arm

Eligibility Criteria

• Age: 3 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Neuren Pharmaceuticals Limited: lead

Study Sites (3)

Neuren PMS-301 Site#111

San Rafael, California, 94903, United States

RECRUITING

Neuren PMS-301 Site#109

Chevy Chase, Maryland, 20815, United States

RECRUITING

Neuren PMS-301 Site#101

New York, New York, 10029, United States

RECRUITING

MeSH Terms

Conditions

Telomeric 22q13 Monosomy Syndrome

Interventions

cyclo-L-glycyl-L-2-allylproline

Central Study Contacts

Medical Information Lead

CONTACT

231-203-8050; medicalinformation@neurenpharma.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) This is a double-blind study in which pediatric participants, caregivers, investigators, and the sponsor are blinded to study drug for the duration of study. Dose escalation, dose modification, and treatment discontinuation will be performed in a blinded manner.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 3, randomized, double-blind, parallel-group (2-arm), placebo-controlled, multicenter study

Study Record Dates

• First Submitted: November 13, 2025
• First Posted: December 15, 2025
• Study Start: November 12, 2025
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): November 15, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)