NNZ-2591 for children with Phelan-McDermid syndrome

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 randomized, placebo-controlled trial will test whether NNZ-2591 helps children ages 3–12 with Phelan-McDermid syndrome over a 13-week treatment period.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 160 (estimated)
• Ages: 3 Years to 12 Years
• Sex: All
• Sponsor: Neuren Pharmaceuticals Limited (Industry-sponsored)
• Locations: 5 sites (San Rafael, California and 4 other locations)
• Trial ID: NCT07281079 on ClinicalTrials.gov

What this trial studies

This Phase 3, randomized, double-blind, parallel-group (2-arm) trial compares orally administered NNZ-2591 to matching placebo in pediatric participants with genetically confirmed Phelan-McDermid syndrome. After a 4-week screening period to confirm eligibility and baseline measures, participants are randomized 1:1 to receive NNZ-2591 or placebo for 13 weeks, followed by a 2-week safety follow-up. Key eligibility includes ages 3–12, documented SHANK3 abnormality, body weight ≥10 kg, a PMSA-S overall score ≥3, and no active regression. The study monitors efficacy and safety outcomes across multiple clinical sites in the United States.

Who should consider this trial

Good fit: Children 3 to 12 years old with a documented disease-causing SHANK3 abnormality, weighing at least 10 kg, with a PMSA-S overall score ≥3 and not undergoing active regression are ideal candidates.

Not a fit: Patients who are actively regressing, on excluded or unstable medication regimens, or with uncontrolled seizures may not receive benefit or may be ineligible.

Why it matters

Potential benefit: If successful, NNZ-2591 could improve core symptoms and everyday functioning for children with Phelan-McDermid syndrome.

How similar studies have performed: Preclinical data and early-stage clinical work on NNZ-2591 suggested potential benefit, but this Phase 3 trial is the first large randomized test in pediatric Phelan-McDermid syndrome.

Eligibility criteria

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.
2. Clinical diagnosis of Phelan-McDermid syndrome with a documented disease-causing genetic abnormality of SHANK3.
3. Body weight ≥ 10 kg at Screening.
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. Current treatment with more than 3 allowable psychotropic medications.
3. Participants with seizures must be controlled on no more than 2 anticonvulsant medications (not counting rescue medications).
4. 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.
5. 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.
6. Abnormal liver function laboratory results during the Screening period, as defined by the protocol
7. Abnormal QT interval on Screening ECG as defined by the protocol.

Where this trial is running

San Rafael, California and 4 other locations

• Neuren PMS-301 Site#111 — San Rafael, California, United States (Recruiting)
• Neuren PMS-301 Site#109 — Chevy Chase, Maryland, United States (Recruiting)
• Neuren PMS-301 Site#106 — Brookline, Massachusetts, United States (Recruiting)
• Neuren PMS-301 Site#101 — New York, New York, United States (Recruiting)
• Neuren PMS-301 Site#108 — Cincinnati, Ohio, United States (Recruiting)

Study contacts

• Study coordinator: Medical Information Lead

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