Trial Outcomes & Findings for Study to Assess the Safety and Tolerability of Idebenone in the Treatment of Friedreich's Ataxia Patients (NCT NCT00697073)

Last Updated: 2023-07-11

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. A total score of 0 points represents the best possible score, and a value of 100 points is the worst possible score. Therefore, a negative change in ICARS score represents an improvement. A higher score also indicates more disability.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

68 participants

Primary outcome timeframe

baseline and 12 months

Results posted on

2023-07-11

Participant Flow

A total of 59 subjects completed the study. Nine subjects did not complete the study. However, neurological efficacy data (ICARS, FARS) are available for Week 52 from 61 patients. All 68 subjects enrolled in this study were included in the Safety population.

Participant milestones

Participant milestones
Measure	High Dose Idebenone Patients ≤ 45 kg/99 lbs: idebenone 1350 mg/day (3 x 150 mg tablets, t.i.d.) Patients \> 45 kg/99 lbs: idebenone 2250 mg/day (5 x 150 mg tablets, t.i.d.)
Overall Study STARTED	68
Overall Study COMPLETED	59
Overall Study NOT COMPLETED	9

Reasons for withdrawal

Reasons for withdrawal
Measure	High Dose Idebenone Patients ≤ 45 kg/99 lbs: idebenone 1350 mg/day (3 x 150 mg tablets, t.i.d.) Patients \> 45 kg/99 lbs: idebenone 2250 mg/day (5 x 150 mg tablets, t.i.d.)
Overall Study Withdrawal by Subject	2
Overall Study Pregnancy	1
Overall Study non compliance and other	6

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	High Dose Idebenone n=68 Participants Patients ≤ 45 kg/99 lbs: idebenone 1350 mg/day (3 x 150 mg tablets, t.i.d.) Patients \> 45 kg/99 lbs: idebenone 2250 mg/day (5 x 150 mg tablets, t.i.d.)
Age, Categorical <=18 years	68 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	14.0 years STANDARD_DEVIATION 2.72 • n=5 Participants
Sex: Female, Male Female	36 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants
Region of Enrollment United States	68 participants n=5 Participants

PRIMARY outcome

Timeframe: baseline and 12 months

Population: A total of 59 subjects completed the study. Nine subjects did not complete the study. However, neurological efficacy data (ICARS, FARS) are available for Week 52 from 61 patients.

Outcome measures

Outcome measures
Measure	High Dose Idebenone n=61 Participants Patients ≤ 45 kg/99 lbs: idebenone 1350 mg/day (3 x 150 mg tablets, t.i.d.) Patients \> 45 kg/99 lbs: idebenone 2250 mg/day (5 x 150 mg tablets, t.i.d.)
Change in ICARS	1.1 units on a scale Standard Deviation 5.64

SECONDARY outcome

Timeframe: baseline and 12 Months

Population: A total of 59 subjects completed the study. Nine subjects did not complete the study. However, neurological efficacy data (ICARS, FARS) are available for Week 52 from 61 patients.

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 consists of three subscales, comprising a general score for ataxia, a score for activities of daily living (ADL) and a neurological examination. The scores can be added to make a total score ranging from 0 to 159. A higher score indicates a greater level of disability.

Outcome measures

Outcome measures
Measure	High Dose Idebenone n=61 Participants Patients ≤ 45 kg/99 lbs: idebenone 1350 mg/day (3 x 150 mg tablets, t.i.d.) Patients \> 45 kg/99 lbs: idebenone 2250 mg/day (5 x 150 mg tablets, t.i.d.)
FARS (Friedreich's Ataxia Rating Scale)	2.3 units on a scale Standard Deviation 5.59

SECONDARY outcome

Timeframe: 12 Months

Population: All 68 subjects enrolled in this study were included in the Safety population.

Outcome measures

Outcome measures
Measure	High Dose Idebenone n=68 Participants Patients ≤ 45 kg/99 lbs: idebenone 1350 mg/day (3 x 150 mg tablets, t.i.d.) Patients \> 45 kg/99 lbs: idebenone 2250 mg/day (5 x 150 mg tablets, t.i.d.)
Nature of Adverse Events Infections and Infestations	117 events
Nature of Adverse Events Gastrointestinal Disorders	97 events
Nature of Adverse Events Musculoskeletal and Connective Tissue Disorders	75 events

SECONDARY outcome

Timeframe: 12 months

Population: All 68 subjects enrolled in this study were included in the Safety population.

Outcome measures

Outcome measures
Measure	High Dose Idebenone n=68 Participants Patients ≤ 45 kg/99 lbs: idebenone 1350 mg/day (3 x 150 mg tablets, t.i.d.) Patients \> 45 kg/99 lbs: idebenone 2250 mg/day (5 x 150 mg tablets, t.i.d.)
Frequency/Number of Mild, Moderate, and Severe Adverse Events mild	30 events
Frequency/Number of Mild, Moderate, and Severe Adverse Events moderate	32 events
Frequency/Number of Mild, Moderate, and Severe Adverse Events severe	4 events

Adverse Events

High Dose Idebenone

Serious events: 4 serious events

Other events: 66 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	High Dose Idebenone n=68 participants at risk Patients ≤ 45 kg/99 lbs: idebenone 1350 mg/day (3 x 150 mg tablets, t.i.d.) Patients \> 45 kg/99 lbs: idebenone 2250 mg/day (5 x 150 mg tablets, t.i.d.)
Cardiac disorders cardiac failure	1.5% 1/68 • Number of events 1
Cardiac disorders tachycardia	1.5% 1/68 • Number of events 1
Endocrine disorders Hyperthyroidism	1.5% 1/68 • Number of events 1
General disorders Hypotension	1.5% 1/68 • Number of events 1
General disorders Deep vein thrombosis	1.5% 1/68 • Number of events 1
General disorders Dehydratation	1.5% 1/68 • Number of events 1
Pregnancy, puerperium and perinatal conditions Pregnancy	1.5% 1/68 • Number of events 1
Pregnancy, puerperium and perinatal conditions intra uterine death	1.5% 1/68 • Number of events 1
Pregnancy, puerperium and perinatal conditions abortion spontaneous	1.5% 1/68 • Number of events 1
Infections and infestations Pharyngitis streptococcal	1.5% 1/68 • Number of events 1
Infections and infestations Pneumonia	1.5% 1/68 • Number of events 1

Other adverse events

Other adverse events
Measure	High Dose Idebenone n=68 participants at risk Patients ≤ 45 kg/99 lbs: idebenone 1350 mg/day (3 x 150 mg tablets, t.i.d.) Patients \> 45 kg/99 lbs: idebenone 2250 mg/day (5 x 150 mg tablets, t.i.d.)
General disorders headache	30.9% 21/68
Infections and infestations upper respiratory tract infection	26.5% 18/68
Gastrointestinal disorders nausea	22.1% 15/68
General disorders pyrexia	20.6% 14/68

Additional Information

Dr Thomas Meier

Santhera

Phone: +41 61 906 8964

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place