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

• ClinicalTrials.gov Identifier: NCT00537680
• Recruitment Status: Completed
• First Posted: October 1, 2007
• Results First Posted: December 29, 2011
• Last Update Posted: February 3, 2012
• Sponsor: Santhera Pharmaceuticals
• Information provided by (Responsible Party): Santhera Pharmaceuticals

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.

Condition or disease	Intervention/treatment	Phase
Friedreich's Ataxia	Drug: Idebenone; Drug: Placebo	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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 Start Date: December 2007
• Actual Primary Completion Date: April 2009
• Actual Study Completion Date: April 2009

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. ICARS [ Time Frame: 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.

   Scores for each subscale quantify the extent of ataxia in each clinically important area. Subscale scores are summed to give a total score ranging from 0 (best) to 100 (worst).

Secondary Outcome Measures :

1. FARS [ Time Frame: 6 Months ]
   Friedreich's Ataxia Rating Scale
2. ADL of FARS [ Time Frame: 6 Months ]
   ADL=Activities of Daily Living
3. FACT [ Time Frame: 6 Months ]
   Friedreich's Ataxia Composite Test

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, California

David Geffen School of Medicine, UCLA

Los Angeles, California, United States, 90095-1769

United States, Pennsylvania

The Children's Hopsital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

Santhera Pharmaceuticals

Investigators

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

More Information

Publications of Results:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Santhera Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00537680
• Other Study ID Numbers: SNT-III-002
• First Posted: October 1, 2007
• Results First Posted: December 29, 2011
• Last Update Posted: February 3, 2012
• Last Verified: February 2012

Keywords provided by Santhera Pharmaceuticals:

Friedreich's Ataxia; Idebenone; ICARS

Additional relevant MeSH terms:

Ataxia; Cerebellar Ataxia; Friedreich Ataxia; Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Spinocerebellar Degenerations; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Mitochondrial Diseases; Metabolic Diseases; Ubiquinone; Idebenone; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs; Micronutrients