Study to Assess the Efficacy, Safety and Tolerability of Idebenone in the Treatment of Friedreich's Ataxia

Study Overview
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Brief Summary
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This study is meant to assess the effectiveness of idebenone on neurological outcome measures in patients with Friedreich's Ataxia over a 6 months period.

Detailed Description
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The study involves 6 clinic visits and upon completion the possibility to join a 12 months extension study where all patients will receive high dose Idebenone.

Official Title
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A Phase III Double-Blind, Randomized, Placebo-Controlled Study of the Efficacy, Safety and Tolerability of Idebenone in the Treatment of Friedreich's Ataxia Patients

Conditions
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Friedreich's Ataxia

Intervention / Treatment
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* Drug: Idebenone
* Drug: Idebenone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Documented diagnosis of Friedreich's Ataxia (FRDA) with confirmed FRDA mutations Patients 8 - 17 years of age at baseline Patients with a body weight greater than 25 kg/55 lbs at baseline Patients able to walk at least 10 meters without accompanying person (ICARS Walking Capacities score ≤6) at screening and baseline Patients who in the opinion of the investigator are able to comply with the requirements of the study, including swallowing the study medication Negative urine pregnancy test at screening and baseline (female patients of childbearing potential) Exclusion criteria: Treatment with idebenone, Coenzyme Q10 or vitamin E (if taken at a dose 5 times above the daily requirement) within the past month Patients with International Cooperative Ataxia Rating Scale (ICARS) score of greater than 54 or less than 10 at screening Pregnancy and/or breast-feeding Clinically significant abnormalities of clinical hematology or biochemistry including, but not limited to, elevations greater than 1.5 times the upper limit of normal of Aspartate Aminotransferase (AST; also known as GOT), Alanine Aminotransferase (ALT; also known as GPT) or creatinine History of abuse of drugs or alcohol Participation in the previous (Phase II) study of idebenone at the National Institutes of Health (NIH) Participation in a trial of another investigational drug within the last 3 months

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

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: Arm 1 - 900 mg/day Idebenone<br>mid dose Idebenone | Drug: Idebenone<br>* Patients ≤ 45 kg/99 lbs: idebenone 450 mg/day; Patients > 45 kg/99 lbs: idebenone 900 mg/day<br>|
| Experimental: Arm 2 - up to 2250 mg/day Idebenone<br>high dose Idebenone | Drug: Idebenone<br>* Patients ≤ 45 kg/99 lbs: idebenone 1350 mg/day; Patients > 45 kg/99 lbs: idebenone 2250 mg/day<br>|
| Placebo Comparator: Arm 3 - Placebo<br>Placebo | Drug: Placebo<br>* Placebo was provided as film-coated tablets that were the same size, weight and appearance as the idebenone tablets.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the International Cooperative Ataxia Rating Scale (ICARS) From Baseline Assessment to Week 24 | International Cooperative Ataxia Rating Scale (ICARS): ICARS consists of a one-hundred-point semi-quantitative scale based upon 19 simple testing manoeuvres compartmentalized into postural and stance disorders, limb ataxia, dysarthria and oculomotor disorders and has been previously used in this patient population with good inter-rater reliability. Minimum score: 0, maximum score 100, higher score indicates greater impairment Calculation details: ICARS score at week 24 minus ICARS score baseline | baseline and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Friedreich's Ataxia Rating Scale (FARS) Scores From Baseline to Week 24 | To compare the efficacy of 6 months' treatment with 2 different doses of idebenone with that of placebo on neurological function as assessed by the Friedreich's Ataxia Rating Scale (FARS) FARS consists of a 25 manoeuvre exam along with 4 quantitative performance measures. The neurological exam covers bulbar function, upper limb coordination, lower limb coordination, peripheral nervous system function, deep tendon reflexes, stability and gait. The use of FARS has been recently validated as a sensitive scale for this population. The FARS exam scores can be added to make a total score ranging from 0 to 159. A higher score indicates a greater level of disability. Calculation details FARS score at week 24 minus FARS score baseline | baseline and 6 months | 
| Activities of Daily Living (ADL) of Friedreich's Ataxia Rating Scale (FARS), Change in ADL (Total Score ) From Baseline to Week 24 | To compare the efficacy of 6 months' treatment with 2 different doses of idebenone with that of placebo on Activities of Daily Living (ADL) assessed by the ADL scale of the Friedreich's Ataxia Rating Scale (FARS) score 0 to 36, higher score indicates greater impairment | baseline and 6 months | 
| Change in the International Cooperative Ataxia Rating Scale (ICARS) From Baseline Assessment to Week 12 | To compare the efficacy of 3 months' treatment with 2 different doses of idebenone with that of placebo on neurological impairment as assessed by the International Cooperative Ataxia Rating Scale (ICARS) International Cooperative Ataxia Rating Scale (ICARS): ICARS consists of a one-hundred-point semi-quantitative scale based upon 19 simple testing manoeuvres compartmentalized into postural and stance disorders, limb ataxia, dysarthria and oculomotor disorders and has been previously used in this patient population with good inter-rater reliability. Minimum score: 0, maximum score 100, higher score indicates greater impairment Calculation details: ICARS score at week 12 minus ICARS score baseline | baseline and 12 weeks | 
| Absolute Change From Baseline to Week 24 in the Relative Wall Thickness (RWT) of the Left Ventricle | To compare the effects of idebenone on cardiac anatomy and function in patients with Friedreich's ataxia (FRDA) as assessed by echocardiography | baseline and 6 months | 
| Percent Change From Baseline to Week 24 in the Relative Wall Thickness (RWT) of the Left Ventricle | To compare the effects of idebenone on cardiac anatomy and function in patients with Friedreich's ataxia (FRDA) as assessed by echocardiography | baseline and 6 months | 
| Absolute Change From Baseline to Week 24 in Left Ventricular Mass Index (LVMI) | To compare the effects of idebenone on cardiac anatomy and function in patients with Friedreich's ataxia (FRDA) as assessed by echocardiography | baseline and 6 months | 
| Percent Change From Baseline to Week 24 in Left Ventricular Mass Index | To compare the effects of idebenone on cardiac anatomy and function in patients with Friedreich's ataxia (FRDA) as assessed by echocardiography | baseline and 6 months | 
| Absolute Change From Baseline to Week 24 in the Thickness of the Posterior Wall (PW) of the Left Ventricle | To compare the effects of idebenone on cardiac anatomy and function in patients with Friedreich's ataxia (FRDA) as assessed by echocardiography | baseline and 6 months | 
| Percent Change From Baseline to Week 24 in the Thickness of the Posterior Wall (PW) of the Left Ventricle | To compare the effects of idebenone on cardiac anatomy and function in patients with Friedreich's ataxia (FRDA) as assessed by echocardiography | baseline and 6 months | 
| Absolute Change From Baseline to Week 24 in the Thickness of the Interventricular Septum (IVS) | To compare the effects of idebenone on cardiac anatomy and function in patients with Friedreich's ataxia (FRDA) as assessed by echocardiography | baseline and 6 months | 
| Percent Change From Baseline to Week 24 in the Thickness of the Interventricular Septum (IVS) | To compare the effects of idebenone on cardiac anatomy and function in patients with Friedreich's ataxia (FRDA) as assessed by echocardiography | baseline and 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Friedreich's Ataxia, Idebenone, ICARS