NNZ-2591 for Phelan-McDermid Syndrome

Overseen By Medical Information Lead

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Neuren Pharmaceuticals Limited

Must not be taking: Psychotropic medications

Disqualifiers: Seizures, Abnormal liver function, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 13 weeks

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called NNZ-2591 for children with Phelan-McDermid Syndrome, a rare genetic disorder affecting development and communication. The goal is to determine if NNZ-2591 is safe and effective compared to a placebo, which contains no active drug. Children aged 3 to 12 with a confirmed genetic cause of Phelan-McDermid Syndrome, who are not losing skills or experiencing uncontrolled seizures, may qualify for this study. Participants will be randomly assigned to receive either NNZ-2591 or a placebo for about 13 weeks. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not clearly state if you must stop taking your current medications, but it requires that any psychotropic or chronic illness medications have stable doses for at least 4 weeks before screening. If you need to stop a medication, it should be done at least 2 weeks before screening.

Is there any evidence suggesting that NNZ-2591 is likely to be safe for humans?

Research has shown that NNZ-2591 is generally safe and well-tolerated in children and teenagers with Phelan-McDermid Syndrome. Most side effects reported in studies were mild or moderate. Only one serious side effect, an inflammation of the stomach and intestines, occurred, but it was unrelated to the study drug. Previous studies also suggest that NNZ-2591 has a good safety record, indicating it doesn't cause many harmful effects. This is encouraging for those considering joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

NNZ-2591 is unique because it represents a novel approach to treating Phelan-McDermid Syndrome, a condition often managed with supportive therapies and symptom-targeted treatments, rather than addressing root causes. Unlike existing options, NNZ-2591 works by targeting pathways in the brain that are thought to be disrupted in this syndrome. This drug is designed to be taken orally, making it potentially more convenient and accessible for patients and caregivers. Researchers are excited about NNZ-2591 because it could offer a new, more effective way to improve cognitive and behavioral symptoms associated with the condition.

What evidence suggests that NNZ-2591 might be an effective treatment for Phelan-McDermid Syndrome?

Research has shown that NNZ-2591 may help treat Phelan-McDermid Syndrome. In earlier studies, participants who took NNZ-2591 showed noticeable improvements in 10 out of 14 important areas. Both doctors and caregivers observed these benefits, indicating wide-ranging positive effects. One study found that the treatment worked consistently well and that higher doses led to greater benefits. In this trial, participants will receive either NNZ-2591 or a placebo at random. This suggests that NNZ-2591 could effectively treat children with Phelan-McDermid Syndrome. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for children with Phelan-McDermid Syndrome. Specific details about who can join are not provided, but typically participants must meet certain health criteria and not be taking conflicting medications.

Inclusion Criteria

My child is between 3 and 12 years old and has Phelan-McDermid syndrome.

Participants with a PMSA-S overall score ≥ 3 at the Screening and Baseline visits

I have Phelan-McDermid syndrome with a confirmed SHANK3 genetic abnormality.

Exclusion Criteria

My medication for chronic illness has been stable for at least 4 weeks.

I have had seizures recently, but only one was due to fever without needing emergency medication.

Abnormal liver function laboratory results during the Screening period, as defined by the protocol

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive either orally administered NNZ-2591 or matching placebo

13 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• NNZ-2591

Trial Overview

The study tests NNZ-2591 against a placebo to see if it's effective and safe for treating Phelan-McDermid Syndrome in kids. It's a Phase 3 trial where patients are randomly assigned to two groups, one receiving the actual drug and the other a placebo.

How Is the Trial Designed?

Group I: NNZ-2591 Arm Experimental Treatment 1 Intervention

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.

Group II: Placebo Arm Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

Neuren Pharmaceuticals Limited

Lead Sponsor

Trials

13

Recruited

920+

Citations

1.

gimopen.org

gimopen.org/article/S2949-7744(25)00170-0/fulltext

Safety, efficacy, and exposure-response of NNZ-2591, a ...

Participants receiving NNZ-2591 experienced statistically significant improvement from baseline for 10 of 14 efficacy outcomes, including both clinician- and ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05025241

An Open-Label Study of Oral NNZ-2591 in Phelan ...

A study of the safety, tolerability and pharmacokinetics of NNZ-2591 and measures of efficacy in children and adolescents with Phelan-McDermid Syndrome.

3.

sciencedirect.com

sciencedirect.com/science/article/pii/S2949774425001700

Safety, efficacy, and exposure-response of NNZ-2591, a ...

Participants receiving NNZ-2591 experienced statistically significant improvement from baseline for 10 of 14 efficacy outcomes, including both clinician- and ...

4.

pmsf.org

pmsf.org/wp-content/uploads/2023/12/Investorpresentation18December2023-1.pdf

NNZ-2591 Phelan-McDermid syndrome Phase 2 trial top- ...

Consistent efficacy and clear dose response for NNZ-2591 in shank3 model ... Top-line results from Pitt Hopkins syndrome Phase 2 trial ...

5.

neurenpharma.com

neurenpharma.com/pipeline1/nnz-2591/phelan-mcdermid-syndrome

Phelan-McDermid Syndrome

On 18 December 2023, Neuren announced top-line results from a Phase 2 clinical trial of NNZ-2591 in children with PMS. Significant improvement was observed by ...

6.

neurenpharma.com

neurenpharma.com/PDF/b2beadcc-0c4d-46e4-9ab0-cfd0e7e8ae1d/SafetyEfficacyandExposureResponseofNNZ2591aSyntheticAnalogofCyclicGlycineProlinecGPanIGF1MetabolitefortheTreatmentofPhelanMcDermidSyndromeinChildrenandAdolescents

Safety, Efficacy, and

aNNZ-2591 doses were titrated up from 4 mg/kg to 8 mg/kg to 12 mg/kg; a data safety monitoring committee reviewed data before each dose increase. Assessments.