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

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

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.

Study Overview

• Status: Completed
• Conditions: Rett Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: EPI-743

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Siena, Italy
    • University of Siena

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: EPI-743 15 mg/kg; Subjects in this arm will receive EPI-743 at a dose of 15 mg/kg three times daily	Drug: EPI-743
Placebo Comparator: Placebo; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Edison Pharmaceuticals Inc

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: March 25, 2013
• First Submitted That Met QC Criteria: March 27, 2013
• First Posted (Estimate): April 2, 2013

Study Record Updates

• Last Update Posted (Actual): July 26, 2018
• Last Update Submitted That Met QC Criteria: July 23, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Rett syndrome; EPI-743; Edison
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Syndrome; Rett Syndrome
• Other Study ID Numbers: OPBGC&RS_12_003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No