Clinical trial NCT00905268: A Study of Efficacy, Safety and Tolerability of Idebenone in the Treatment of Friedreich's Ataxia (FRDA) Patients
Official title: A Phase III Double-blind, Randomised, Placebo-controlled Study of the Efficacy, Safety and Tolerability of Idebenone in the Treatment of Friedreich's Ataxia Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Friedreich's Ataxia
Keywords: FRDA
idebenone
FRDA disease
Lead sponsor: Santhera Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2009-05-20
Enrollment: 232
Sex: ALL
Minimum age (years): 8
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this trial is to study the efficacy, safety and tolerability of idebenone in 12 months of treatment in children and adults with Friedreich's Ataxia. This is a randomised placebo-controlled double-blind trial conducted in Europe. Efficacy outcomes include measures of neurological impairment and function, and measures of the heart.

Detailed description: Idebenone, a short-chain analogue of Co-enzyme Q10 (CoQ10), has the potential to moderate underlying causes of Friedreich's Ataxia through its antioxidant activity and its role as an electron carrier in the respiratory chain promoting mitochondrial ATP production.

The current 12-month placebo-controlled treatment study in 232 patients aims to confirm the positive effect of idebenone on neurological function, as for instance observed in the recent 48-patient, 6-month NICOSIA study in children, using the International Cooperative Ataxia Rating Scale (ICARS) and the newly developed Friedreich's Ataxia Rating Scale (FARS).

In addition, the study aims to confirm the positive effect on cardiomyopathy associated with FRDA observed in several small studies. Cardiac anatomy and function will be assessed using echocardiography, tissue Doppler imaging and cardiac MRI methods in patients with FRDA cardiomyopathy. In addition exercise capacity, measured as peak workload, will be assessed in patients able to comply with a modified exercise protocol.

Eligibility criteria: Inclusion Criteria:

* Documented diagnosis of FRDA with confirmed FRDA mutations
* Patients 8 years of age or older at baseline
* Patients with body weight ≥ 25kg
* Patients who in the opinion of the investigator are able to comply with the requirements of the study, including swallowing the medication
* Negative urine pregnancy test at screening and at baseline (women of childbearing potential)

Exclusion Criteria:

* Treatment with idebenone or Coenzyme Q10 within the past 1 month
* Pregnancy and/or breast-feeding
* Clinically significant abnormalities of clinical haematology or biochemistry including, but not limited to, elevations greater than 1.5 times the upper limit of normal of SGOT, SGPT, or creatinine
* Past or present history of abuse of drugs or alcohol

Primary outcomes:
measure: Absolute Change in International Cooperative Ataxia Rating Scale (ICARS) Scores From Baseline Assessment to Week 52
timeFrame: Baseline and week 52
Secondary outcomes:
measure: Absolute Change in Friedreich's Ataxia Rating Scale (FARS) Scores From Baseline Assessment to Week 52
timeFrame: Baseline and week 52
measure: Proportion of Patients Improving (Responding) on ICARS by a Clinically Relevant Margin
timeFrame: week 52
measure: Proportion of Patients Improving on Left Ventricular Peak Systolic Strain Rate or Showing a Reduction in Left Ventricular Mass Index (LVMI) With no Worsening in Strain Rate
timeFrame: 1 year
measure: Change in Peak Systolic Strain Rate From Baseline to Week 52
timeFrame: 1 year
measure: Change in Peak Workload From Baseline to Week 52
timeFrame: 1 year
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Universitätsklinik Innsbruck
city: Bruxelles
country: Belgium
facility: Hôpital Erasme - Université Libre de Bruxelles
city: Paris
country: France
facility: Hôpital de la Salpêtrière - INSERM U679, Neurologie et Thérapeutique expérimentale
city: Berlin
country: Germany
facility: HELIOS Klinikum BerlinBuch
city: Bonn
country: Germany
facility: Neurologische Universitätsklinik und Poliklinik- Universitätsklinikum Bonn
city: Freiburg
country: Germany
facility: Klinik II, Neuropädiatrie u.Muskelerkrankungen- Universitätsklinik Freiburg
city: Göttingen
country: Germany
facility: Zentrum für Neurologische Medizin
city: Hamburg
country: Germany
facility: UKE Hamburg Neuropädiatrie-Zentum für Frauen, Kinder und Jugendmedizin
city: München
country: Germany
facility: Neurologische Klinik- klinikum Grosshadern
city: Tübingen
country: Germany
facility: Neurologische Universitätsklinik und Poliklinik
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: London
country: United Kingdom
facility: National Hospital for Neurology & Neurosurgery
city: Newcastle
country: United Kingdom
facility: University of Newcastle upon Tyne -Mitochondrial Research Group
Study officials:
affiliation: Dept of Molecular Neuroscience, Institute of Neurology. The National Hospital, University college London.
name: Nick Wood, Professor
role: PRINCIPAL_INVESTIGATOR
References: