Friedreich's Ataxia
Conditions
Keywords
Friedreich's Ataxia, Idebenone, ICARS
Brief summary
This study is meant to assess the effectiveness of idebenone on neurological outcome measures in patients with Friedreich's Ataxia over a 6 months period.
Detailed description
The study involves 6 clinic visits and upon completion the possibility to join a 12 months extension study where all patients will receive high dose Idebenone.
Interventions
DRUGIdebenone
Patients ≤ 45 kg/99 lbs: idebenone 450 mg/day; Patients \> 45 kg/99 lbs: idebenone 900 mg/day
DRUGPlacebo
Placebo was provided as film-coated tablets that were the same size, weight and appearance as the idebenone tablets.
Sponsors
Santhera Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
8 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Documented diagnosis of Friedreich's Ataxia (FRDA) with confirmed FRDA mutations * Patients 8 - 17 years of age at baseline * Patients with a body weight greater than 25 kg/55 lbs at baseline * Patients able to walk at least 10 meters without accompanying person (ICARS Walking Capacities score ≤6) at screening and baseline * Patients who in the opinion of the investigator are able to comply with the requirements of the study, including swallowing the study medication * Negative urine pregnancy test at screening and baseline (female patients of childbearing potential)
Exclusion criteria
* Treatment with idebenone, Coenzyme Q10 or vitamin E (if taken at a dose 5 times above the daily requirement) within the past month * Patients with International Cooperative Ataxia Rating Scale (ICARS) score of greater than 54 or less than 10 at screening * Pregnancy and/or breast-feeding * Clinically significant abnormalities of clinical hematology or biochemistry including, but not limited to, elevations greater than 1.5 times the upper limit of normal of Aspartate Aminotransferase (AST; also known as GOT), Alanine Aminotransferase (ALT; also known as GPT) or creatinine * History of abuse of drugs or alcohol * Participation in the previous (Phase II) study of idebenone at the National Institutes of Health (NIH) * Participation in a trial of another investigational drug within the last 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the International Cooperative Ataxia Rating Scale (ICARS) From Baseline Assessment to Week 24 | baseline and 6 months | International Cooperative Ataxia Rating Scale (ICARS): ICARS consists of a one-hundred-point semi-quantitative scale based upon 19 simple testing manoeuvres compartmentalized into postural and stance disorders, limb ataxia, dysarthria and oculomotor disorders and has been previously used in this patient population with good inter-rater reliability. Minimum score: 0, maximum score 100, higher score indicates greater impairment Calculation details: ICARS score at week 24 minus ICARS score baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Activities of Daily Living (ADL) of Friedreich's Ataxia Rating Scale (FARS), Change in ADL (Total Score ) From Baseline to Week 24 | baseline and 6 months | To compare the efficacy of 6 months' treatment with 2 different doses of idebenone with that of placebo on Activities of Daily Living (ADL) assessed by the ADL scale of the Friedreich's Ataxia Rating Scale (FARS) score 0 to 36, higher score indicates greater impairment |
| Change in the International Cooperative Ataxia Rating Scale (ICARS) From Baseline Assessment to Week 12 | baseline and 12 weeks | To compare the efficacy of 3 months' treatment with 2 different doses of idebenone with that of placebo on neurological impairment as assessed by the International Cooperative Ataxia Rating Scale (ICARS) International Cooperative Ataxia Rating Scale (ICARS): ICARS consists of a one-hundred-point semi-quantitative scale based upon 19 simple testing manoeuvres compartmentalized into postural and stance disorders, limb ataxia, dysarthria and oculomotor disorders and has been previously used in this patient population with good inter-rater reliability. Minimum score: 0, maximum score 100, higher score indicates greater impairment Calculation details: ICARS score at week 12 minus ICARS score baseline |
| Absolute Change From Baseline to Week 24 in the Relative Wall Thickness (RWT) of the Left Ventricle | baseline and 6 months | To compare the effects of idebenone on cardiac anatomy and function in patients with Friedreich's ataxia (FRDA) as assessed by echocardiography |
| Percent Change From Baseline to Week 24 in the Relative Wall Thickness (RWT) of the Left Ventricle | baseline and 6 months | To compare the effects of idebenone on cardiac anatomy and function in patients with Friedreich's ataxia (FRDA) as assessed by echocardiography |
| Absolute Change From Baseline to Week 24 in Left Ventricular Mass Index (LVMI) | baseline and 6 months | To compare the effects of idebenone on cardiac anatomy and function in patients with Friedreich's ataxia (FRDA) as assessed by echocardiography |
| Change in Friedreich's Ataxia Rating Scale (FARS) Scores From Baseline to Week 24 | baseline and 6 months | To compare the efficacy of 6 months' treatment with 2 different doses of idebenone with that of placebo on neurological function as assessed by the Friedreich's Ataxia Rating Scale (FARS) FARS consists of a 25 manoeuvre exam along with 4 quantitative performance measures. The neurological exam covers bulbar function, upper limb coordination, lower limb coordination, peripheral nervous system function, deep tendon reflexes, stability and gait. The use of FARS has been recently validated as a sensitive scale for this population. The FARS exam scores can be added to make a total score ranging from 0 to 159. A higher score indicates a greater level of disability. Calculation details FARS score at week 24 minus FARS score baseline |
| Absolute Change From Baseline to Week 24 in the Thickness of the Posterior Wall (PW) of the Left Ventricle | baseline and 6 months | To compare the effects of idebenone on cardiac anatomy and function in patients with Friedreich's ataxia (FRDA) as assessed by echocardiography |
| Percent Change From Baseline to Week 24 in the Thickness of the Posterior Wall (PW) of the Left Ventricle | baseline and 6 months | To compare the effects of idebenone on cardiac anatomy and function in patients with Friedreich's ataxia (FRDA) as assessed by echocardiography |
| Absolute Change From Baseline to Week 24 in the Thickness of the Interventricular Septum (IVS) | baseline and 6 months | To compare the effects of idebenone on cardiac anatomy and function in patients with Friedreich's ataxia (FRDA) as assessed by echocardiography |
| Percent Change From Baseline to Week 24 in the Thickness of the Interventricular Septum (IVS) | baseline and 24 weeks | To compare the effects of idebenone on cardiac anatomy and function in patients with Friedreich's ataxia (FRDA) as assessed by echocardiography |
| Percent Change From Baseline to Week 24 in Left Ventricular Mass Index | baseline and 6 months | To compare the effects of idebenone on cardiac anatomy and function in patients with Friedreich's ataxia (FRDA) as assessed by echocardiography |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mid Dose Idebenone 25 kg/55 lbs to ≤45 kg/99 lbs: idebenone 450 mg/day (1 x 150 mg tablet, t.i.d.) \>45 kg/99 lbs: idebenone 900 mg/day (2 x 150 mg tablet, t.i.d.) | 22 |
| High Dose Idebenone 25 kg/55 lbs to ≤45 kg/99 lbs: idebenone 1350 mg/day (2 x 150 mg tablet, t.i.d.) \>45 kg/99 lbs: idebenone 2250 mg/day (2 x 150 mg tablet, t.i.d.) | 24 |
| Placebo Placebo was provided as film-coated tablets that were the same size, weight and appearance as the idebenone tablets. | 24 |
| Total | 70 |
Baseline characteristics
| Characteristic | High Dose Idebenone | Placebo | Mid Dose Idebenone | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 24 Participants | 24 Participants | 22 Participants | 70 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 13.44 years STANDARD_DEVIATION 3.03 | 13.69 years STANDARD_DEVIATION 2.77 | 13.93 years STANDARD_DEVIATION 2.54 | 13.68 years STANDARD_DEVIATION 2.76 |
| Region of Enrollment United States | 24 participants | 24 participants | 22 participants | 70 participants |
| Sex: Female, Male Female | 14 Participants | 16 Participants | 7 Participants | 37 Participants |
| Sex: Female, Male Male | 10 Participants | 8 Participants | 15 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 18 / 22 | 23 / 24 | 21 / 24 |
| serious Total, serious adverse events | 0 / 22 | 2 / 24 | 0 / 24 |
Outcome results
Primary
Change in the International Cooperative Ataxia Rating Scale (ICARS) From Baseline Assessment to Week 24
International Cooperative Ataxia Rating Scale (ICARS): ICARS consists of a one-hundred-point semi-quantitative scale based upon 19 simple testing manoeuvres compartmentalized into postural and stance disorders, limb ataxia, dysarthria and oculomotor disorders and has been previously used in this patient population with good inter-rater reliability. Minimum score: 0, maximum score 100, higher score indicates greater impairment Calculation details: ICARS score at week 24 minus ICARS score baseline
Time frame: baseline and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mid Dose Idebenone | Change in the International Cooperative Ataxia Rating Scale (ICARS) From Baseline Assessment to Week 24 | -2.5 ICARS points | Standard Deviation 6.3 |
| High Dose Idebenone | Change in the International Cooperative Ataxia Rating Scale (ICARS) From Baseline Assessment to Week 24 | -2.4 ICARS points | Standard Deviation 4.8 |
| Placebo | Change in the International Cooperative Ataxia Rating Scale (ICARS) From Baseline Assessment to Week 24 | -1.3 ICARS points | Standard Deviation 4.4 |
Secondary
Absolute Change From Baseline to Week 24 in Left Ventricular Mass Index (LVMI)
To compare the effects of idebenone on cardiac anatomy and function in patients with Friedreich's ataxia (FRDA) as assessed by echocardiography
Time frame: baseline and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mid Dose Idebenone | Absolute Change From Baseline to Week 24 in Left Ventricular Mass Index (LVMI) | -3.06 g/m2 | Standard Deviation 6.23 |
| High Dose Idebenone | Absolute Change From Baseline to Week 24 in Left Ventricular Mass Index (LVMI) | -2.56 g/m2 | Standard Deviation 4.27 |
| Placebo | Absolute Change From Baseline to Week 24 in Left Ventricular Mass Index (LVMI) | -1.26 g/m2 | Standard Deviation 6.47 |
Secondary
Absolute Change From Baseline to Week 24 in the Relative Wall Thickness (RWT) of the Left Ventricle
To compare the effects of idebenone on cardiac anatomy and function in patients with Friedreich's ataxia (FRDA) as assessed by echocardiography
Time frame: baseline and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mid Dose Idebenone | Absolute Change From Baseline to Week 24 in the Relative Wall Thickness (RWT) of the Left Ventricle | -0.032 cm | Standard Deviation 0.096 |
| High Dose Idebenone | Absolute Change From Baseline to Week 24 in the Relative Wall Thickness (RWT) of the Left Ventricle | 0.007 cm | Standard Deviation 0.071 |
| Placebo | Absolute Change From Baseline to Week 24 in the Relative Wall Thickness (RWT) of the Left Ventricle | 0.010 cm | Standard Deviation 0.097 |
Secondary
Absolute Change From Baseline to Week 24 in the Thickness of the Interventricular Septum (IVS)
To compare the effects of idebenone on cardiac anatomy and function in patients with Friedreich's ataxia (FRDA) as assessed by echocardiography
Time frame: baseline and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mid Dose Idebenone | Absolute Change From Baseline to Week 24 in the Thickness of the Interventricular Septum (IVS) | -0.014 cm | Standard Deviation 0.1983 |
| High Dose Idebenone | Absolute Change From Baseline to Week 24 in the Thickness of the Interventricular Septum (IVS) | 0.021 cm | Standard Deviation 0.1474 |
| Placebo | Absolute Change From Baseline to Week 24 in the Thickness of the Interventricular Septum (IVS) | 0.063 cm | Standard Deviation 0.1952 |
Secondary
Absolute Change From Baseline to Week 24 in the Thickness of the Posterior Wall (PW) of the Left Ventricle
To compare the effects of idebenone on cardiac anatomy and function in patients with Friedreich's ataxia (FRDA) as assessed by echocardiography
Time frame: baseline and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mid Dose Idebenone | Absolute Change From Baseline to Week 24 in the Thickness of the Posterior Wall (PW) of the Left Ventricle | -0.018 cm | Standard Deviation 0.137 |
| High Dose Idebenone | Absolute Change From Baseline to Week 24 in the Thickness of the Posterior Wall (PW) of the Left Ventricle | -0.004 cm | Standard Deviation 0.112 |
| Placebo | Absolute Change From Baseline to Week 24 in the Thickness of the Posterior Wall (PW) of the Left Ventricle | -0.038 cm | Standard Deviation 0.153 |
Secondary
Activities of Daily Living (ADL) of Friedreich's Ataxia Rating Scale (FARS), Change in ADL (Total Score ) From Baseline to Week 24
To compare the efficacy of 6 months' treatment with 2 different doses of idebenone with that of placebo on Activities of Daily Living (ADL) assessed by the ADL scale of the Friedreich's Ataxia Rating Scale (FARS) score 0 to 36, higher score indicates greater impairment
Time frame: baseline and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mid Dose Idebenone | Activities of Daily Living (ADL) of Friedreich's Ataxia Rating Scale (FARS), Change in ADL (Total Score ) From Baseline to Week 24 | 0.2 ADL points | Standard Deviation 2.45 |
| High Dose Idebenone | Activities of Daily Living (ADL) of Friedreich's Ataxia Rating Scale (FARS), Change in ADL (Total Score ) From Baseline to Week 24 | 0.6 ADL points | Standard Deviation 3.13 |
| Placebo | Activities of Daily Living (ADL) of Friedreich's Ataxia Rating Scale (FARS), Change in ADL (Total Score ) From Baseline to Week 24 | 1.0 ADL points | Standard Deviation 2.97 |
Secondary
Change in Friedreich's Ataxia Rating Scale (FARS) Scores From Baseline to Week 24
To compare the efficacy of 6 months' treatment with 2 different doses of idebenone with that of placebo on neurological function as assessed by the Friedreich's Ataxia Rating Scale (FARS) FARS consists of a 25 manoeuvre exam along with 4 quantitative performance measures. The neurological exam covers bulbar function, upper limb coordination, lower limb coordination, peripheral nervous system function, deep tendon reflexes, stability and gait. The use of FARS has been recently validated as a sensitive scale for this population. The FARS exam scores can be added to make a total score ranging from 0 to 159. A higher score indicates a greater level of disability. Calculation details FARS score at week 24 minus FARS score baseline
Time frame: baseline and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mid Dose Idebenone | Change in Friedreich's Ataxia Rating Scale (FARS) Scores From Baseline to Week 24 | -1.6 FARS score | Standard Deviation 6.52 |
| High Dose Idebenone | Change in Friedreich's Ataxia Rating Scale (FARS) Scores From Baseline to Week 24 | -1.2 FARS score | Standard Deviation 4.53 |
| Placebo | Change in Friedreich's Ataxia Rating Scale (FARS) Scores From Baseline to Week 24 | 0.6 FARS score | Standard Deviation 5.91 |
Secondary
Change in the International Cooperative Ataxia Rating Scale (ICARS) From Baseline Assessment to Week 12
To compare the efficacy of 3 months' treatment with 2 different doses of idebenone with that of placebo on neurological impairment as assessed by the International Cooperative Ataxia Rating Scale (ICARS) International Cooperative Ataxia Rating Scale (ICARS): ICARS consists of a one-hundred-point semi-quantitative scale based upon 19 simple testing manoeuvres compartmentalized into postural and stance disorders, limb ataxia, dysarthria and oculomotor disorders and has been previously used in this patient population with good inter-rater reliability. Minimum score: 0, maximum score 100, higher score indicates greater impairment Calculation details: ICARS score at week 12 minus ICARS score baseline
Time frame: baseline and 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mid Dose Idebenone | Change in the International Cooperative Ataxia Rating Scale (ICARS) From Baseline Assessment to Week 12 | -1.5 ICARS points | Standard Deviation 5.35 |
| High Dose Idebenone | Change in the International Cooperative Ataxia Rating Scale (ICARS) From Baseline Assessment to Week 12 | -1.6 ICARS points | Standard Deviation 5.53 |
| Placebo | Change in the International Cooperative Ataxia Rating Scale (ICARS) From Baseline Assessment to Week 12 | -3.0 ICARS points | Standard Deviation 3.52 |
Secondary
Percent Change From Baseline to Week 24 in Left Ventricular Mass Index
To compare the effects of idebenone on cardiac anatomy and function in patients with Friedreich's ataxia (FRDA) as assessed by echocardiography
Time frame: baseline and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mid Dose Idebenone | Percent Change From Baseline to Week 24 in Left Ventricular Mass Index | -4.5 % change | Standard Deviation 11.302 |
| High Dose Idebenone | Percent Change From Baseline to Week 24 in Left Ventricular Mass Index | -4.9 % change | Standard Deviation 8.713 |
| Placebo | Percent Change From Baseline to Week 24 in Left Ventricular Mass Index | -1.7 % change | Standard Deviation 12.382 |
Secondary
Percent Change From Baseline to Week 24 in the Relative Wall Thickness (RWT) of the Left Ventricle
To compare the effects of idebenone on cardiac anatomy and function in patients with Friedreich's ataxia (FRDA) as assessed by echocardiography
Time frame: baseline and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mid Dose Idebenone | Percent Change From Baseline to Week 24 in the Relative Wall Thickness (RWT) of the Left Ventricle | -3.32 % change | Standard Deviation 15.3 |
| High Dose Idebenone | Percent Change From Baseline to Week 24 in the Relative Wall Thickness (RWT) of the Left Ventricle | 1.53 % change | Standard Deviation 12.56 |
| Placebo | Percent Change From Baseline to Week 24 in the Relative Wall Thickness (RWT) of the Left Ventricle | 2.65 % change | Standard Deviation 17.135 |
Secondary
Percent Change From Baseline to Week 24 in the Thickness of the Interventricular Septum (IVS)
To compare the effects of idebenone on cardiac anatomy and function in patients with Friedreich's ataxia (FRDA) as assessed by echocardiography
Time frame: baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mid Dose Idebenone | Percent Change From Baseline to Week 24 in the Thickness of the Interventricular Septum (IVS) | 1.3 % change | Standard Deviation 18.16 |
| High Dose Idebenone | Percent Change From Baseline to Week 24 in the Thickness of the Interventricular Septum (IVS) | 2.6 % change | Standard Deviation 13.084 |
| Placebo | Percent Change From Baseline to Week 24 in the Thickness of the Interventricular Septum (IVS) | 7.8 % change | Standard Deviation 19.48 |
Secondary
Percent Change From Baseline to Week 24 in the Thickness of the Posterior Wall (PW) of the Left Ventricle
To compare the effects of idebenone on cardiac anatomy and function in patients with Friedreich's ataxia (FRDA) as assessed by echocardiography
Time frame: baseline and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mid Dose Idebenone | Percent Change From Baseline to Week 24 in the Thickness of the Posterior Wall (PW) of the Left Ventricle | -0.075 % change | Standard Deviation 13.379 |
| High Dose Idebenone | Percent Change From Baseline to Week 24 in the Thickness of the Posterior Wall (PW) of the Left Ventricle | 0.12 % change | Standard Deviation 12.549 |
| Placebo | Percent Change From Baseline to Week 24 in the Thickness of the Posterior Wall (PW) of the Left Ventricle | -3.04 % change | Standard Deviation 14.651 |