A Safety Study of NNZ-2566 in Pediatric Rett Syndrome

Study Overview
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Brief Summary
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The purpose of this study is to determine whether NNZ-2566 is safe and well tolerated in the treatment of Rett syndrome in children and adolescents.

Detailed Description
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Rett syndrome is a neurodevelopmental disorder primarily affecting females. The disorder is characterized by apparent normal development in early infancy (6-18 months), followed by a period of regression with onset of systemic and neurological signs. The CNS symptoms of Rett syndrome include learning disability, autism symptomatology and epilepsy and these can be severe and highly debilitating. Affected individuals also show signs of autonomic dysfunction, reflected in cardiovascular and respiratory abnormalities. There is no currently effective treatment for Rett syndrome. This study will investigate the safety, tolerability and blood pharmacokinetics of treatment with oral administration of NNZ-2566 at 50 mg/kg, 100 mg/kg, 200 mg/kg BID, or placebo BID, in children and adolescent females with Rett syndrome. The study also will also investigate measures of efficacy and biomarkers during treatment.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Dose-ranging Study of the Safety and Pharmacokinetics of Oral NNZ-2566 in Pediatric Rett Syndrome

Conditions
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Rett Syndrome

Intervention / Treatment
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* Drug: NNZ-2566
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of classic/typical Rett syndrome with a documented mutation of the MeCP2 gene. Age 5 - 15 years. Weight at Screening and Baseline between 15.0 kg-100.0 kg (at least 15.0 kg and no greater than 100.0 kg). Each subject must be able to swallow the study medication provided as a liquid solution, or via gastrostomy tube. Exclusion Criteria: Actively undergoing neurological regression Abnormal QT interval, prolongation or significant cardiovascular history. Current treatment with insulin. Anti-convulsants with liver enzyme inducing effects. Unstable seizure profile. Excluded concomitant medications. Current clinically significant (as determined by the investigator). cardiovascular, renal, hepatic, or respiratory disease. Gastrointestinal disease which may interfere with the absorption, distribution, metabolism or excretion of the study medication. History of, or current cerebrovascular disease or brain trauma. History of, or current clinically significant endocrine disorder, e.g. hypo- or hyperthyroidism, or diabetes mellitus. History of, or current, malignancy. Significant hearing and/or visual impairments that may affect ability to complete the test procedures. Allergy to strawberry.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 15 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NNZ-2566<br>Glycyl-L-2-Methylpropyl-L-Glutamic Acid | Drug: NNZ-2566<br>* Glycyl-L-2-Methylpropyl-L-Glutamic Acid (NNZ-2566) supplied as a lyophilized powder for reconstitution with strawberry flavored solution 0.5% v/v in Water for Injection.<br>* Other names: trofinetide;|
| Placebo Comparator: Placebo (strawberry flavored solution)<br>Strawberry flavored solution and Water for Injection | Drug: Placebo<br>* Strawberry flavored solution and Water for Injection<br>* Other names: Strawberry flavoring;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Incidence of adverse events (AEs), including serious adverse events (SAEs), will be compared across the three NNZ-2566 doses and placebo. SAEs and AEs will be examined throughout the study. | Through study completion, an average of 11 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Motor Behaviour Assessment Scale (MBA) |  | Through study completion, an average of 11 weeks | 
| Clinical Global Impression of Improvement (CGI-I) |  | Through study completion, an average of 11 weeks | 
| Caregiver Top 3 Concerns via a Visual Analogue Scale (VAS) |  | Through study completion, an average of 11 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autism, Rett's syndrome, Rett disorder, Rett's disorder, Ataxia