Phase 2 Study of EPI-743 for Treatment of Rett Syndrome

Study Overview
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Brief Summary
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Rett syndrome is a severe neurodevelopmental disorder that primarily affects female children. Rett syndrome is characterized by significant elevation in blood markers of oxidative stress. EPI-743 is a novel therapeutic with demonstrated efficacy and safety in the treatment of disorders characterized by oxidative stress. The purpose of this study is to examine the safety and efficacy of EPI-743 in a population of children with Rett syndrome.

Official Title
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A Phase 2A Randomized, Placebo Controlled Trial of EPI-743 in Children With Rett Syndrome

Conditions
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Rett Syndrome

Intervention / Treatment
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* Drug: EPI-743
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Rett syndrome with disease stage 1-2 Abnormality of at least two disease biomarker levels Confirmed MeCP2 mutation Patient or patient's guardian able to consent and comply with protocol requirements Abstention from use of Coenzyme Q10, vitamin E and Idebenone two weeks prior to enrollment into the study Exclusion Criteria: Any condition, which in the opinion of the investigator could compromise the subject's safety or adherence to treatment with EPI-743. Clinically significant allergy or hypersensitivity to EPI-743 or to any of the excipients of with EPI-743 (eg., sesame oil). Clinically significant allergy or hypersensitivity to Vitamin E Lack of confirmation of MeCP2 mutation Clinical history of bleeding or abnormal baseline PT/PTT Diagnosis of any other concurrent inborn error of metabolism Hepatic insufficiency with LFTs greater than 3 times upper limit of normal Renal insufficiency requiring dialysis End stage cardiac failure Fat malabsorption syndromes precluding drug absorption

Ages Eligible for Study
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Maximum Age: 18 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 |
| --- | --- |
| Active Comparator: EPI-743 15 mg/kg<br>Subjects in this arm will receive EPI-743 at a dose of 15 mg/kg three times daily | Drug: EPI-743<br> <br> |
| Placebo Comparator: Placebo<br>Subjects in this arm will receive placebo at a volume equivalent to the volume of EPI-743 they would receive if in active group based on their weight | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rett Syndrome Clinical Severity Sore | Measure of disease progression | Change at six months from baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxidative Stress Biomarkers |  | Change at six months from baseline | 
| Head circumference |  | Change at six months from baseline | 
| Rett syndrome behavioral questionnaire |  | Change at six months from baseline | 
| PedsQL |  | Change at six months from baseline | 
| Number of Drug-related adverse and serious adverse events |  | Six months | 
| Respiratory Disturbance Index (RDI) | RDI will be determined on polysomnography study | Change at six months from baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rett syndrome, EPI-743, Edison