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

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

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.

Study Overview

• Status: Completed
• Conditions: Friedreich's Ataxia
• Intervention / Treatment: Drug: idebenone; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 232
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Universitätsklinik Innsbruck
• Belgium
  • Bruxelles, Belgium, 1070
    • Hôpital Erasme - Université Libre de Bruxelles
• France
  • Paris, France, 75651
    • Hôpital de la Salpétrière - INSERM U679, Neurologie et Thérapeutique expérimentale
• Germany
  • Berlin, Germany, 13125
    • HELIOS Klinikum BerlinBuch
  • Bonn, Germany, 53105
    • Neurologische Universitätsklinik und Poliklinik- Universitätsklinikum Bonn
  • Freiburg, Germany, 79106
    • Klinik II, Neuropädiatrie u.Muskelerkrankungen- Universitätsklinik Freiburg
  • Göttingen, Germany, 37073
    • Zentrum für Neurologische Medizin
  • Hamburg, Germany, 20246
    • UKE Hamburg Neuropädiatrie-Zentum für Frauen, Kinder und Jugendmedizin
  • München, Germany, 81377
    • Neurologische Klinik- klinikum Grosshadern
  • Tübingen, Germany, 72076
    • Neurologische Universitätsklinik und Poliklinik
• Netherlands
  • Groningen, Netherlands, 9700 RB
    • University Medical Center Groningen
• United Kingdom
  • London, United Kingdom, WC1N 3BG
    • National Hospital for Neurology & Neurosurgery
  • Newcastle, United Kingdom, NE2 4HH
    • University of Newcastle upon Tyne -Mitochondrial Research Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: Idebenone; Patients under/equal 45 kg: idebenone 180 mg/day Patients over 45 kg: idebenone 360 mg/day	Drug: idebenone; 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
Experimental: Group B: Idebenone; Patients under/equal 45 kg: idebenone 450 mg/day Patients over 45 kg: idebenone 900 mg/day	Drug: idebenone; 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
Experimental: C: Idebenone; Patients under/equal 45 kg: idebenone 1350 mg/day Patients over 45 kg: idebenone 2250 mg/day	Drug: idebenone; 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
Placebo Comparator: D: Placebo; placebo	Drug: Placebo; 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change in International Cooperative Ataxia Rating Scale (ICARS) Scores From Baseline Assessment to Week 52	The International Cooperative Ataxia Rating Scale (ICARS) is a commonly used evaluation and is composed of four clinical sub-scores involving the following: posture and gait, limb coordination, speech and oculomotor function.The ICARS score is the total sum of the sub scores and ranges from 0 to 100, with 100 indicative of the most severely affected outcome.	Baseline and week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change in Friedreich's Ataxia Rating Scale (FARS) Scores From Baseline Assessment to Week 52	The Friedreich Ataxia Rating Scale (FARS) is made up of a measure of ataxia, and activities of daily living subscale and a neurological subscale. The scores from the three subscales are added to generate a total score ranging from 0 to 159, with a higher score indicating a greater level of disability.	Baseline and week 52
Proportion of Patients Improving (Responding) on ICARS by a Clinically Relevant Margin	The International Cooperative Ataxia Rating Scale (ICARS) is a commonly used evaluation and is composed of four clinical sub-scores involving the following: posture and gait, limb coordination, speech and oculomotor function.The ICARS score is the total sum of the sub scores and ranges from 0 to 100, with 100 indicative of the most severely affected outcome. ICARS Responder Analysis at Week 52: Percentage of subjects Improving by 2.5 Points or More.	week 52
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	(In the statistical analysis sub-population presenting with cardiac involvement as defined by the FRDA cardiomyopathy criteria)	1 year
Change in Peak Systolic Strain Rate From Baseline to Week 52	Mean Change of Peak systolic longitudinal strain rate (PSLSR) from Baseline to Week 52 in subjects with cardiac involvement (FRDA-CM criteria), where positive value in PSLSR is a deterioration and negative value an improvement.	1 year
Change in Peak Workload From Baseline to Week 52	Assessed by a modified exercise test, in a subset of patients able to undertake this. Wpeak has been calculated from the following formula: Workload last fully completed stage + (seconds completed in last stage / 60 * (4 [if arm ergonometry] or 10 [if leg ergonometry])).	1 year

Collaborators and Investigators

• Sponsor: Santhera Pharmaceuticals
• Investigators: Principal Investigator: Nick Wood, Professor, Dept of Molecular Neuroscience, Institute of Neurology. The National Hospital, University college London.

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: May 19, 2009
• First Submitted That Met QC Criteria: May 19, 2009
• First Posted (Estimate): May 20, 2009

Study Record Updates

• Last Update Posted (Estimate): June 27, 2016
• Last Update Submitted That Met QC Criteria: May 19, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: FRDA; idebenone; FRDA disease
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Genetic Diseases, Inborn; Neurodegenerative Diseases; Dyskinesias; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Mitochondrial Diseases; Cerebellar Diseases; Spinocerebellar Degenerations; Ataxia; Cerebellar Ataxia; Friedreich Ataxia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Antioxidants; Idebenone
• Other Study ID Numbers: SNT-III-001