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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Santhera Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00905268
First received: May 19, 2009
Last updated: May 19, 2016
Last verified: May 2016
  Purpose
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.

Condition Intervention Phase
Friedreich's Ataxia
Drug: idebenone
Drug: Placebo
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Santhera Pharmaceuticals:

Primary Outcome Measures:
  • Absolute Change in International Cooperative Ataxia Rating Scale (ICARS) Scores From Baseline Assessment to Week 52 [ Time Frame: Baseline and week 52 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Absolute Change in Friedreich's Ataxia Rating Scale (FARS) Scores From Baseline Assessment to Week 52 [ Time Frame: Baseline and week 52 ] [ Designated as safety issue: No ]
    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.

  • Proportion of Patients Improving (Responding) on ICARS by a Clinically Relevant Margin [ Time Frame: week 52 ] [ Designated as safety issue: No ]

    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.


  • 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 [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    (In the statistical analysis sub-population presenting with cardiac involvement as defined by the FRDA cardiomyopathy criteria)

  • Change in Peak Systolic Strain Rate From Baseline to Week 52 [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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.

  • Change in Peak Workload From Baseline to Week 52 [ Time Frame: 1 year ] [ Designated as safety issue: No ]

    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])).



Enrollment: 232
Study Start Date: April 2006
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

Ages Eligible for Study:   8 Years and older   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00905268

Locations
Austria
Universitätsklinik Innsbruck
Innsbruck, Austria, 6020
Belgium
Hôpital Erasme - Université Libre de Bruxelles
Bruxelles, Belgium, 1070
France
Hôpital de la Salpêtrière - INSERM U679, Neurologie et Thérapeutique expérimentale
Paris, France, 75651
Germany
HELIOS Klinikum BerlinBuch
Berlin, Germany, 13125
Neurologische Universitätsklinik und Poliklinik- Universitätsklinikum Bonn
Bonn, Germany, 53105
Klinik II, Neuropädiatrie u.Muskelerkrankungen- Universitätsklinik Freiburg
Freiburg, Germany, 79106
Zentrum für Neurologische Medizin
Göttingen, Germany, 37073
UKE Hamburg Neuropädiatrie-Zentum für Frauen, Kinder und Jugendmedizin
Hamburg, Germany, 20246
Neurologische Klinik- klinikum Grosshadern
München, Germany, 81377
Neurologische Universitätsklinik und Poliklinik
Tübingen, Germany, 72076
Netherlands
University Medical Center Groningen
Groningen, Netherlands, 9700 RB
United Kingdom
National Hospital for Neurology & Neurosurgery
London, United Kingdom, WC1N 3BG
University of Newcastle upon Tyne -Mitochondrial Research Group
Newcastle, United Kingdom, NE2 4HH
Sponsors and Collaborators
Santhera Pharmaceuticals
Investigators
Principal Investigator: Nick Wood, Professor Dept of Molecular Neuroscience, Institute of Neurology. The National Hospital, University college London.
  More Information

Responsible Party: Santhera Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00905268     History of Changes
Other Study ID Numbers: SNT-III-001 
Study First Received: May 19, 2009
Results First Received: October 20, 2015
Last Updated: May 19, 2016
Health Authority: Austria: Federal Office for Safety in Health Care
Belgium: Institutional Review Board
Belgium: Federal Agency for Medicinal Products and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Institutional Ethical Committee
Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Netherlands: Medical Ethics Review Committee (METC)
Netherlands: Ministry of Health, Welfare and Sport

Keywords provided by Santhera Pharmaceuticals:
FRDA
idebenone
FRDA disease

Additional relevant MeSH terms:
Ataxia
Cerebellar Ataxia
Friedreich Ataxia
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Cerebellar Diseases
Brain Diseases
Central Nervous System Diseases
Spinocerebellar Degenerations
Spinal Cord Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Mitochondrial Diseases
Metabolic Diseases
Idebenone
Ubiquinone
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on September 27, 2016