Trial Outcomes & Findings for Study to Assess the Efficacy, Safety and Tolerability of Idebenone in the Treatment of Friedreich's Ataxia (NCT NCT00537680)

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

70 participants

Primary outcome timeframe

baseline and 6 months

Results posted on

2023-07-11

Participant Flow

Participant milestones

Participant milestones
Measure	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.)	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.)	Placebo Placebo was provided as film-coated tablets that were the same size, weight and appearance as the idebenone tablets.
Overall Study STARTED	22	24	24
Overall Study COMPLETED	22	22	24
Overall Study NOT COMPLETED	0	2	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study to Assess the Efficacy, Safety and Tolerability of Idebenone in the Treatment of Friedreich's Ataxia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Mid Dose Idebenone n=22 Participants 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.)	High Dose Idebenone n=24 Participants 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.)	Placebo n=24 Participants Placebo was provided as film-coated tablets that were the same size, weight and appearance as the idebenone tablets.	Total n=70 Participants Total of all reporting groups
Age, Categorical <=18 years	22 Participants n=5 Participants	24 Participants n=7 Participants	24 Participants n=5 Participants	70 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	13.93 years STANDARD_DEVIATION 2.54 • n=5 Participants	13.44 years STANDARD_DEVIATION 3.03 • n=7 Participants	13.69 years STANDARD_DEVIATION 2.77 • n=5 Participants	13.68 years STANDARD_DEVIATION 2.76 • n=4 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	14 Participants n=7 Participants	16 Participants n=5 Participants	37 Participants n=4 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	10 Participants n=7 Participants	8 Participants n=5 Participants	33 Participants n=4 Participants
Region of Enrollment United States	22 participants n=5 Participants	24 participants n=7 Participants	24 participants n=5 Participants	70 participants n=4 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Mid Dose Idebenone n=22 Participants 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.)	High Dose Idebenone n=24 Participants 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.)	Placebo n=24 Participants Placebo was provided as film-coated tablets that were the same size, weight and appearance as the idebenone tablets.
Change in the International Cooperative Ataxia Rating Scale (ICARS) From Baseline Assessment to Week 24	-2.5 ICARS points Standard Deviation 6.3	-2.4 ICARS points Standard Deviation 4.8	-1.3 ICARS points Standard Deviation 4.4

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Mid Dose Idebenone n=22 Participants 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.)	High Dose Idebenone n=24 Participants 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.)	Placebo n=24 Participants Placebo was provided as film-coated tablets that were the same size, weight and appearance as the idebenone tablets.
Change in Friedreich's Ataxia Rating Scale (FARS) Scores From Baseline to Week 24	-1.6 FARS score Standard Deviation 6.52	-1.2 FARS score Standard Deviation 4.53	0.6 FARS score Standard Deviation 5.91

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Mid Dose Idebenone n=22 Participants 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.)	High Dose Idebenone n=24 Participants 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.)	Placebo n=24 Participants Placebo was provided as film-coated tablets that were the same size, weight and appearance as the idebenone tablets.
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	0.6 ADL points Standard Deviation 3.13	1.0 ADL points Standard Deviation 2.97

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Mid Dose Idebenone n=22 Participants 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.)	High Dose Idebenone n=24 Participants 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.)	Placebo n=24 Participants Placebo was provided as film-coated tablets that were the same size, weight and appearance as the idebenone tablets.
Change in the International Cooperative Ataxia Rating Scale (ICARS) From Baseline Assessment to Week 12	-1.5 ICARS points Standard Deviation 5.35	-1.6 ICARS points Standard Deviation 5.53	-3.0 ICARS points Standard Deviation 3.52

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Mid Dose Idebenone n=22 Participants 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.)	High Dose Idebenone n=24 Participants 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.)	Placebo n=24 Participants Placebo was provided as film-coated tablets that were the same size, weight and appearance as the idebenone tablets.
Absolute Change From Baseline to Week 24 in the Relative Wall Thickness (RWT) of the Left Ventricle	-0.032 cm Standard Deviation 0.096	0.007 cm Standard Deviation 0.071	0.010 cm Standard Deviation 0.097

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Mid Dose Idebenone n=22 Participants 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.)	High Dose Idebenone n=24 Participants 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.)	Placebo n=24 Participants Placebo was provided as film-coated tablets that were the same size, weight and appearance as the idebenone tablets.
Percent Change From Baseline to Week 24 in the Relative Wall Thickness (RWT) of the Left Ventricle	-3.32 % change Standard Deviation 15.300	1.53 % change Standard Deviation 12.560	2.65 % change Standard Deviation 17.135

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Mid Dose Idebenone n=22 Participants 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.)	High Dose Idebenone n=24 Participants 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.)	Placebo n=24 Participants Placebo was provided as film-coated tablets that were the same size, weight and appearance as the idebenone tablets.
Absolute Change From Baseline to Week 24 in Left Ventricular Mass Index (LVMI)	-3.06 g/m2 Standard Deviation 6.23	-2.56 g/m2 Standard Deviation 4.27	-1.26 g/m2 Standard Deviation 6.47

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Mid Dose Idebenone n=22 Participants 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.)	High Dose Idebenone n=24 Participants 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.)	Placebo n=24 Participants Placebo was provided as film-coated tablets that were the same size, weight and appearance as the idebenone tablets.
Percent Change From Baseline to Week 24 in Left Ventricular Mass Index	-4.5 % change Standard Deviation 11.302	-4.9 % change Standard Deviation 8.713	-1.7 % change Standard Deviation 12.382

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Mid Dose Idebenone n=22 Participants 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.)	High Dose Idebenone n=24 Participants 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.)	Placebo n=24 Participants Placebo was provided as film-coated tablets that were the same size, weight and appearance as the idebenone tablets.
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	-0.004 cm Standard Deviation 0.112	-0.038 cm Standard Deviation 0.153

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Mid Dose Idebenone n=22 Participants 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.)	High Dose Idebenone n=24 Participants 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.)	Placebo n=24 Participants Placebo was provided as film-coated tablets that were the same size, weight and appearance as the idebenone tablets.
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	0.12 % change Standard Deviation 12.549	-3.04 % change Standard Deviation 14.651

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Mid Dose Idebenone n=22 Participants 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.)	High Dose Idebenone n=24 Participants 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.)	Placebo n=24 Participants Placebo was provided as film-coated tablets that were the same size, weight and appearance as the idebenone tablets.
Absolute Change From Baseline to Week 24 in the Thickness of the Interventricular Septum (IVS)	-0.014 cm Standard Deviation 0.1983	0.021 cm Standard Deviation 0.1474	0.063 cm Standard Deviation 0.1952

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Mid Dose Idebenone n=22 Participants 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.)	High Dose Idebenone n=24 Participants 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.)	Placebo n=24 Participants Placebo was provided as film-coated tablets that were the same size, weight and appearance as the idebenone tablets.
Percent Change From Baseline to Week 24 in the Thickness of the Interventricular Septum (IVS)	1.3 % change Standard Deviation 18.160	2.6 % change Standard Deviation 13.084	7.8 % change Standard Deviation 19.480

Adverse Events

Mid Dose Idebenone

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

High Dose Idebenone

Serious events: 2 serious events

Other events: 23 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Mid Dose Idebenone n=22 participants at risk 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.)	High Dose Idebenone n=24 participants at risk 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.)	Placebo n=24 participants at risk Placebo was provided as film-coated tablets that were the same size, weight and appearance as the idebenone tablets.
Blood and lymphatic system disorders idiopathic thrombocytopenic purpura	0.00% 0/22 "0" means none.	4.2% 1/24 • Number of events 1 "0" means none.	0.00% 0/24 "0" means none.
General disorders chest pain	0.00% 0/22 "0" means none.	4.2% 1/24 • Number of events 2 "0" means none.	0.00% 0/24 "0" means none.

Other adverse events

Other adverse events
Measure	Mid Dose Idebenone n=22 participants at risk 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.)	High Dose Idebenone n=24 participants at risk 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.)	Placebo n=24 participants at risk Placebo was provided as film-coated tablets that were the same size, weight and appearance as the idebenone tablets.
Infections and infestations Infections	50.0% 11/22 "0" means none.	62.5% 15/24 "0" means none.	66.7% 16/24 "0" means none.
Nervous system disorders Nervous system disorders	45.5% 10/22 "0" means none.	58.3% 14/24 "0" means none.	50.0% 12/24 "0" means none.
Gastrointestinal disorders Gastrointestinal disorders	36.4% 8/22 "0" means none.	62.5% 15/24 "0" means none.	50.0% 12/24 "0" means none.
General disorders General disorders	45.5% 10/22 "0" means none.	37.5% 9/24 "0" means none.	37.5% 9/24 "0" means none.
Musculoskeletal and connective tissue disorders Musculoskeletal & connective tissue disorders	31.8% 7/22 "0" means none.	41.7% 10/24 "0" means none.	29.2% 7/24 "0" means none.

Additional Information

Dr Thomas Meier

Santhera Pharmaceuticals

Phone: +41619068964

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place