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

A Phase III Double-Blind, Randomized, Placebo-Controlled Study of the Efficacy, Safety and Tolerability of Idebenone in the Treatment of Friedreich's Ataxia Patients

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.

Study Overview

• Status: Completed
• Conditions: Friedreich's Ataxia
• Intervention / Treatment: Drug: Idebenone; Drug: Idebenone; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095-1769
      • David Geffen School of Medicine, UCLA
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hopsital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1 - 900 mg/day Idebenone; mid dose Idebenone	Drug: Idebenone; Patients ≤ 45 kg/99 lbs: idebenone 450 mg/day; Patients > 45 kg/99 lbs: idebenone 900 mg/day; Drug: Idebenone; Patients ≤ 45 kg/99 lbs: idebenone 1350 mg/day; Patients > 45 kg/99 lbs: idebenone 2250 mg/day
Experimental: Arm 2 - up to 2250 mg/day Idebenone; high dose Idebenone	Drug: Idebenone; Patients ≤ 45 kg/99 lbs: idebenone 450 mg/day; Patients > 45 kg/99 lbs: idebenone 900 mg/day; Drug: Idebenone; Patients ≤ 45 kg/99 lbs: idebenone 1350 mg/day; Patients > 45 kg/99 lbs: idebenone 2250 mg/day
Placebo Comparator: Arm 3 - Placebo; Placebo	Drug: Placebo; Placebo was provided as film-coated tablets that were the same size, weight and appearance as the idebenone tablets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	baseline and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	baseline and 6 months
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	baseline and 6 months
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	baseline and 12 weeks
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	baseline and 6 months
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	baseline and 6 months
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	baseline and 6 months
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	baseline and 6 months
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	baseline and 6 months
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	baseline and 6 months
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	baseline and 6 months
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	baseline and 24 weeks

Collaborators and Investigators

• Sponsor: Santhera Pharmaceuticals
• Investigators: Principal Investigator: David Lynch, MD, Children's Hospital of Philadelphia; Principal Investigator: Susan Perlman, MD, University of California, Los Angeles

Publications and helpful links

General Publications

• Meier T, Perlman SL, Rummey C, Coppard NJ, Lynch DR. Assessment of neurological efficacy of idebenone in pediatric patients with Friedreich's ataxia: data from a 6-month controlled study followed by a 12-month open-label extension study. J Neurol. 2012 Feb;259(2):284-91. doi: 10.1007/s00415-011-6174-y. Epub 2011 Jul 22.
• Lagedrost SJ, Sutton MS, Cohen MS, Satou GM, Kaufman BD, Perlman SL, Rummey C, Meier T, Lynch DR. Idebenone in Friedreich ataxia cardiomyopathy-results from a 6-month phase III study (IONIA). Am Heart J. 2011 Mar;161(3):639-645.e1. doi: 10.1016/j.ahj.2010.10.038. Epub 2011 Jan 31.
• Lynch DR, Perlman SL, Meier T. A phase 3, double-blind, placebo-controlled trial of idebenone in friedreich ataxia. Arch Neurol. 2010 Aug;67(8):941-7. doi: 10.1001/archneurol.2010.168.

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: September 7, 2007
• First Submitted That Met QC Criteria: September 28, 2007
• First Posted (Estimated): October 1, 2007

Study Record Updates

• Last Update Posted (Actual): July 11, 2023
• Last Update Submitted That Met QC Criteria: June 22, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Friedreich's Ataxia; ICARS; Idebenone
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Genetic Diseases, Inborn; Neurodegenerative Diseases; Dyskinesias; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Mitochondrial Diseases; Cerebellar Diseases; Spinocerebellar Degenerations; Ataxia; Cerebellar Ataxia; Friedreich Ataxia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Antioxidants; Ubiquinone; Idebenone
• Other Study ID Numbers: SNT-III-002