A Study of Efficacy, Safety and Tolerability of Idebenone in the Treatment of Friedreich's Ataxia (FRDA) Patients

Friedreich's Ataxia Clinical Trial

— MICONOS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00905268
• Other study ID #: SNT-III-001
• Status: Completed
• Phase: Phase 3
• First received: May 19, 2009
• Last updated: August 20, 2010
• Start date: April 2006
• Est. completion date: January 2010

Study information

• Verified date: August 2010
• Source: Santhera Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Federal Office for Safety in Health CareBelgium: Institutional Review BoardBelgium: Federal Agency for Medicinal Products and Health ProductsFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)France: Institutional Ethical CommitteeGermany: Ethics CommissionGermany: Federal Institute for Drugs and Medical DevicesUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: Research Ethics CommitteeNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Netherlands: Medical Ethics Review Committee (METC)Netherlands: Ministry of Health, Welfare and Sport
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 232
• Est. completion date: January 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 8 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ataxia
• Cerebellar Ataxia
• Friedreich Ataxia
• Friedreich's Ataxia

Intervention

Drug:
• idebenone
12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
• Placebo
12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.

Locations

Country	Name	City	State
Austria	Universitätsklinik Innsbruck	Innsbruck
Belgium	Hôpital Erasme - Université Libre de Bruxelles	Bruxelles
France	Hôpital de la Salpêtrière - INSERM U679, Neurologie et Thérapeutique expérimentale	Paris
Germany	HELIOS Klinikum BerlinBuch	Berlin
Germany	Neurologische Universitätsklinik und Poliklinik- Universitätsklinikum Bonn	Bonn
Germany	Klinik II, Neuropädiatrie u.Muskelerkrankungen- Universitätsklinik Freiburg	Freiburg
Germany	Zentrum für Neurologische Medizin	Göttingen
Germany	UKE Hamburg Neuropädiatrie-Zentum für Frauen, Kinder und Jugendmedizin	Hamburg
Germany	Neurologische Klinik- klinikum Grosshadern	München
Germany	Neurologische Universitätsklinik und Poliklinik	Tübingen
Netherlands	University Medical Center Groningen	Groningen
United Kingdom	National Hospital for Neurology & Neurosurgery	London
United Kingdom	University of Newcastle upon Tyne -Mitochondrial Research Group	Newcastle

Sponsors (1)

Lead Sponsor	Collaborator
Santhera Pharmaceuticals

Countries where clinical trial is conducted

Austria,  Belgium,  France,  Germany,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Absolute change in International Cooperative Ataxia Rating Scale (ICARS) scores from baseline assessment to Week 52	(Where the patient populations are not normally distributed for ICARS the responder analysis will be used as the primary endpoint and a clinically relevant margin of 2.5 ICARS points will be applied)	1 year	No
Secondary	Absolute change in Friedreich's Ataxia Rating Scale (FARS) scores from baseline assessment to Week 52		1 year	No
Secondary	Proportion of patients improving (responding) on ICARS by a clinically relevant margin	(Where the patient populations are not normally distributed for ICARS the responder analysis will be used as the primary endpoint and a clinically relevant margin of 2.5 ICARS points will be applied.)	1 year	No
Secondary	Proportion of patients improving onon left ventricular peak systolic strain rate or showing a reduction in Left Ventricular Mass Index (LVMI) with no worsening in strain rate	(In the statistical analysis sub-population presenting with cardiac involvement as defined by the FRDA cardiomyopathy criteria)	1 year	No
Secondary	Change in peak systolic strain rate from baseline to Week 52		1 year	No
Secondary	Change in peak workload from baseline to Week 52, as assessed by a modified exercise test, in a subset of patients able to undertake this		1 year	No