search
Back to results

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

Primary Purpose

Friedreich's Ataxia

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Idebenone
Idebenone
Placebo
Sponsored by
Santhera Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Friedreich's Ataxia focused on measuring Friedreich's Ataxia, Idebenone, ICARS

Eligibility Criteria

8 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • David Geffen School of Medicine, UCLA
  • The Children's Hopsital of Philadelphia

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Arm 1 - 900 mg/day Idebenone

Arm 2 - up to 2250 mg/day Idebenone

Arm 3 - Placebo

Arm Description

mid dose Idebenone

high dose Idebenone

Placebo

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
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
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
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
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
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
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
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
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
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
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

Full Information

First Posted
September 7, 2007
Last Updated
June 22, 2023
Sponsor
Santhera Pharmaceuticals
search

1. Study Identification

Unique Protocol Identification Number
NCT00537680
Brief Title
Study to Assess the Efficacy, Safety and Tolerability of Idebenone in the Treatment of Friedreich's Ataxia
Acronym
IONIA
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
December 2007 (undefined)
Primary Completion Date
April 2009 (Actual)
Study Completion Date
April 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Santhera Pharmaceuticals

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Friedreich's Ataxia
Keywords
Friedreich's Ataxia, Idebenone, ICARS

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
70 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1 - 900 mg/day Idebenone
Arm Type
Experimental
Arm Description
mid dose Idebenone
Arm Title
Arm 2 - up to 2250 mg/day Idebenone
Arm Type
Experimental
Arm Description
high dose Idebenone
Arm Title
Arm 3 - Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
Idebenone
Intervention Description
Patients ≤ 45 kg/99 lbs: idebenone 450 mg/day; Patients > 45 kg/99 lbs: idebenone 900 mg/day
Intervention Type
Drug
Intervention Name(s)
Idebenone
Intervention Description
Patients ≤ 45 kg/99 lbs: idebenone 1350 mg/day; Patients > 45 kg/99 lbs: idebenone 2250 mg/day
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo was provided as film-coated tablets that were the same size, weight and appearance as the idebenone tablets.
Primary Outcome Measure Information:
Title
Change in the International Cooperative Ataxia Rating Scale (ICARS) From Baseline Assessment to Week 24
Description
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
Secondary Outcome Measure Information:
Title
Change in Friedreich's Ataxia Rating Scale (FARS) Scores From Baseline to Week 24
Description
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
Title
Activities of Daily Living (ADL) of Friedreich's Ataxia Rating Scale (FARS), Change in ADL (Total Score ) From Baseline to Week 24
Description
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
Title
Change in the International Cooperative Ataxia Rating Scale (ICARS) From Baseline Assessment to Week 12
Description
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
Title
Absolute Change From Baseline to Week 24 in the Relative Wall Thickness (RWT) of the Left Ventricle
Description
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
Title
Percent Change From Baseline to Week 24 in the Relative Wall Thickness (RWT) of the Left Ventricle
Description
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
Title
Absolute Change From Baseline to Week 24 in Left Ventricular Mass Index (LVMI)
Description
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
Title
Percent Change From Baseline to Week 24 in Left Ventricular Mass Index
Description
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
Title
Absolute Change From Baseline to Week 24 in the Thickness of the Posterior Wall (PW) of the Left Ventricle
Description
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
Title
Percent Change From Baseline to Week 24 in the Thickness of the Posterior Wall (PW) of the Left Ventricle
Description
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
Title
Absolute Change From Baseline to Week 24 in the Thickness of the Interventricular Septum (IVS)
Description
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
Title
Percent Change From Baseline to Week 24 in the Thickness of the Interventricular Septum (IVS)
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
8 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Susan Perlman, MD
Organizational Affiliation
University of California, Los Angeles
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
David Lynch, MD
Organizational Affiliation
Children's Hospital of Philadelphia
Official's Role
Principal Investigator
Facility Information:
Facility Name
David Geffen School of Medicine, UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-1769
Country
United States
Facility Name
The Children's Hopsital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
21779958
Citation
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.
Results Reference
result
PubMed Identifier
21392622
Citation
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.
Results Reference
derived
PubMed Identifier
20697044
Citation
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.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs