Friedreich's AtaxiaPhase 3MICONOSNCT00905268
A Study of Efficacy, Safety and Tolerability of Idebenone in the Treatment of Friedreich's Ataxia (FRDA) Patients
A Phase 3 study testing idebenone in people with Friedreich's Ataxia, run by Santhera Pharmaceuticals at 13 sites in 6 countries.
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. Read more about this study
- Who is it for?
- Ages 8 years and older
- Conditions the study is for
- Friedreich's Ataxia
- What is being tested?
- idebenone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 232 participants
- Where
- 13 sitesin 6 countries
- Study dates
- Apr 2006to Jan 2010
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
13 sites in 6 countries.
13 sites in 6 countries
Germany7 sites
HELIOS Klinikum BerlinBuch
Berlin, 13125
Neurologische Universitätsklinik und Poliklinik- Universitätsklinikum Bonn
Bonn, 53105
Klinik II, Neuropädiatrie u.Muskelerkrankungen- Universitätsklinik Freiburg
Freiburg im Breisgau, 79106
Zentrum für Neurologische Medizin
Göttingen, 37073
UKE Hamburg Neuropädiatrie-Zentum für Frauen, Kinder und Jugendmedizin
Hamburg, 20246
Neurologische Klinik- klinikum Grosshadern
München, 81377
Neurologische Universitätsklinik und Poliklinik
Tübingen, 72076
United Kingdom2 sites
National Hospital for Neurology & Neurosurgery
London, WC1N 3BG
University of Newcastle upon Tyne -Mitochondrial Research Group
Newcastle, NE2 4HH
France1 site
Hôpital de la Salpêtrière - INSERM U679, Neurologie et Thérapeutique expérimentale
Paris, 75651
About this study
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
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.
Read the 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.
- Conditions
- Friedreich's Ataxia
- Being tested
- idebenone, Placebo
- Keywords
- FRDA, idebenone, FRDA disease
- Medical subject headings
- Friedreich Ataxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
idebenoneDrug
12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
PlaceboDrug
12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
| Study group | Role | What they receive |
|---|---|---|
| Group A: Idebenone | Experimental | Patients under/equal 45 kg: idebenone 180 mg/day Patients over 45 kg: idebenone 360 mg/day Receives: Drug: idebenone |
| Group B: Idebenone | Experimental | Patients under/equal 45 kg: idebenone 450 mg/day Patients over 45 kg: idebenone 900 mg/day Receives: Drug: idebenone |
| C: Idebenone | Experimental | Patients under/equal 45 kg: idebenone 1350 mg/day Patients over 45 kg: idebenone 2250 mg/day Receives: Drug: idebenone |
| D: Placebo | Placebo comparator | placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and week 52
Secondary outcomes (5)
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.
Measured: 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.
Measured: 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)
Measured: 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.
Measured: 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])).
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2009 (estimated)
- Study startApr 2006
- Primary completionJan 2010
- Study completionJan 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Friedreich's AtaxiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 232 participants (actual)
Sponsor and investigators
- Lead sponsor
- Santhera Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Nick Wood, Professor, Principal investigator, Dept of Molecular Neuroscience, Institute of Neurology. The National Hospital, University college London.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00905268
- Sponsor's protocol ID
- SNT-III-001
- Acronym
- MICONOS
- Status last verified
- May 2016
- First submitted
- 19 May 2009
- Last updated
- 27 Jun 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00905268
- Acronym / sponsor ID
- MICONOS / SNT-III-001
- Conditions
- Friedreich's Ataxia
- Keywords
- FRDA, idebenone, FRDA disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 232 participants (actual)
- Lead sponsor
- Santhera PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Apr 2006
- Primary completion
- Jan 2010 (actual)
- Study completion
- Jan 2010 (actual)
- First posted
- 20 May 2009 (estimated)
- Results
- Posted 27 Jun 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group A: Idebenone | Experimental | Drug: idebenonePatients under/equal 45 kg: idebenone 180 mg/day Patients over 45 kg: idebenone 360 mg/day |
| Group B: Idebenone | Experimental | Drug: idebenonePatients under/equal 45 kg: idebenone 450 mg/day Patients over 45 kg: idebenone 900 mg/day |
| C: Idebenone | Experimental | Drug: idebenonePatients under/equal 45 kg: idebenone 1350 mg/day Patients over 45 kg: idebenone 2250 mg/day |
| D: Placebo | Placebo comparator | Drug: Placeboplacebo |
Who may qualify
- Ages
- 8 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| idebenone12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals. | Drug | C: Idebenone, Group A: Idebenone, Group B: Idebenone |
| Placebo12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals. | Drug | D: Placebo |
Primary outcome
Absolute Change in International Cooperative Ataxia Rating Scale (ICARS) Scores From Baseline Assessment to Week 52
Time frame: Baseline and 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.
5 secondary outcomes
Absolute Change in Friedreich's Ataxia Rating Scale (FARS) Scores From Baseline Assessment to Week 52
Time frame: Baseline and week 52
Proportion of Patients Improving (Responding) on ICARS by a Clinically Relevant Margin
Time frame: 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
Time frame: 1 year
Change in Peak Systolic Strain Rate From Baseline to Week 52
Time frame: 1 year
Change in Peak Workload From Baseline to Week 52
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nick Wood, Professor principal investigator
Dept of Molecular Neuroscience, Institute of Neurology. The National Hospital, University college London.
13 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing idebenone in people with Friedreich's Ataxia, run by Santhera Pharmaceuticals at 13 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Germany, United Kingdom, Austria, Belgium, France and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jun 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Absolute Change in International Cooperative Ataxia Rating Scale (ICARS) Scores From Baseline Assessment to Week 52 (time frame: Baseline and week 52). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2016.