Study to Assess Efficacy,Safety and Tolerability of Idebenone in the Treatment of Leber's Hereditary Optic Neuropathy - Full Text View

Purpose

This study is meant to assess the effectiveness of idebenone on visual function measures in patients with Leber's Hereditary Optic Neuropathy over a 6 months period.

Condition	Intervention	Phase
Leber's Hereditary Optic Neuropathy	Drug: Idebenone Drug: Placebo	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Double-Blind, Randomised, Placebo-Controlled Study of the Efficacy, Safety and Tolerability of Idebenone in the Treatment of Patients With Leber's Hereditary Optic Neuropathy

Resource links provided by NLM:

Genetics Home Reference related topics: ataxia neuropathy spectrum Charcot-Marie-Tooth disease childhood myocerebrohepatopathy spectrum deoxyguanosine kinase deficiency hereditary neuropathy with liability to pressure palsies Leber hereditary optic neuropathy Lenz microphthalmia syndrome mitochondrial neurogastrointestinal encephalopathy disease myoclonic epilepsy myopathy sensory ataxia oculofaciocardiodental syndrome Peters plus syndrome

U.S. FDA Resources

Further study details as provided by Santhera Pharmaceuticals:

Primary Outcome Measures:

Best recovery of logMAR visual acuity between baseline and Week 24 in either right or left eye [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change in the patient's best logMAR visual acuity between baseline and week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Change in scotoma area in both eyes [ Time Frame: Day -1, Week 4, Week 12, Week 24 ] [ Designated as safety issue: No ]
Change in optic nerve fibre layer thickness in both eyes [ Time Frame: Day -1, Week 4, Week 12, Week 24 ] [ Designated as safety issue: No ]
Colour contrast sensitivity in both eyes (in a subset of patients) [ Time Frame: Day -1, Week 4, Week 12, Week 24 ] [ Designated as safety issue: No ]
logMAR visual acuity as a continuous variable in both eyes [ Time Frame: Screening, Day -1, Week 4, Week 12, Week 24, Week 28 ] [ Designated as safety issue: No ]
Clinical Global Impression of Change [ Time Frame: Week 4, Week 12 and Week 24 ] [ Designated as safety issue: No ]
Change in Health-Related Quality of Life (HRQOL) [ Time Frame: Day -1, Week 4, Week 12, Week 24 ] [ Designated as safety issue: No ]
Change in self-reported general energy levels [ Time Frame: Day -1, Week 4, Week 12, Week 24, Week 28 ] [ Designated as safety issue: No ]
Proportion of patients in which visual acuity in the initially least affected eye does not deteriorate to 1.0 log MAR or more ( in LHON patients with eye still less affected than 0.5 logMAR at trial entry) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Plasma levels of idebenone matched to measures of efficacy and safety [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
• Best visual acuity at Week 24 (best eye at Week 24) compared to best visual acuity at Baseline (best eye at Baseline) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• Count of eyes/ patients for which the visual acuity improves between baseline and week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	84
Study Start Date:	November 2007
Study Completion Date:	February 2010
Primary Completion Date:	February 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Idebenone	Drug: Idebenone Idebenone 900 mg/day
Placebo Comparator: 2 Placebo	Drug: Placebo Placebo

Detailed Description:

The study involves 6 clinic visits.

Eligibility

Ages Eligible for Study:	14 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age > or = 14 years and < 65 years
Impaired visual acuity in at least one eye due to LHON
Onset of visual loss due to LHON lies five years or less prior to Baseline
Confirmation of either G11778A, T14484C or G3460A LHON mtDNA mutations at >60% in blood
No explanation for the visual failure besides LHON
Body weight ≥ 45 kg
Negative urine pregnancy test at Screening and at Baseline (women of childbearing potential).

Exclusion Criteria:

Treatment with Coenzyme Q10 or idebenone within 1 month prior to Baseline
Pregnancy and/or breast-feeding
Weekly alcohol intake 35 units (men) or 24 units (women)
Current drug abuse
Clinically significant abnormalities of clinical haematology or biochemistry including, but not limited to, elevations greater than 2 times the upper limit of normal of AST, ALT or creatinine
Participation in another clinical trial of any investigational drug within 3 months prior to Baseline
Other factor that, in the investigator's opinion, excludes the patient from entering the study

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00747487

Locations

Canada, Quebec
Unité de recherche clinique Ophtalmologie- Hopital Notre-Dame
Montreal, Quebec, Canada, H2L 4M1
Germany
Klinikum der Universität München - Grosshadern, Neurologische Klinik und Poliklinik
Munich, Germany, 81377
United Kingdom
Clinical Research Facility, 4th Floor Leazes Wing, Royal Victoria Infirmary
Newcastle Upon Tyne, United Kingdom, NE1 4LP

Sponsors and Collaborators

Santhera Pharmaceuticals

Investigators

Principal Investigator:	Prof Patrick F Chinnery, MD	Clinical Research Facility, 4th Floor Leazes Wing, Royal Victoria Infirmary
Principal Investigator:	Prof Thomas Klopstock, MD	Klinikum der Universität München - Grosshadern, Neurologische Klinik und Poliklinik

More Information

Additional Information:

Website for LHON patients in the U.K. This link exits the ClinicalTrials.gov site

Publications:

Klopstock T, Yu-Wai-Man P, Dimitriadis K, Rouleau J, Heck S, Bailie M, Atawan A, Chattopadhyay S, Schubert M, Garip A, Kernt M, Petraki D, Rummey C, Leinonen M, Metz G, Griffiths PG, Meier T, Chinnery PF. A randomized placebo-controlled trial of idebenone in Leber's hereditary optic neuropathy. Brain. 2011 Jul 25; [Epub ahead of print]

Rudolph G, Dimitriadis K, Büchner B, Heck S, Al-Tamami J, Seidensticker F, Rummey C, Leinonen M, Meier T, Klopstock T. Effects of Idebenone on Color Vision in Patients With Leber Hereditary Optic Neuropathy. J Neuroophthalmol. 2012 Dec 21. [Epub ahead of print]

Responsible Party:	Thomas Meier, PhD / Chief Scientific Officer, Santhera Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00747487 History of Changes
Other Study ID Numbers:	SNT-II-003
Study First Received:	September 4, 2008
Last Updated:	January 2, 2013
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices United Kingdom: Medicines and Healthcare Products Regulatory Agency Canada: Health Canada

Keywords provided by Santhera Pharmaceuticals:

Leber
LHON
Leber's Hereditary Optic Neuropathy
Idebenone

Additional relevant MeSH terms:

Optic Atrophy, Hereditary, Leber
Optic Atrophies, Hereditary
Eye Diseases, Hereditary
Optic Nerve Diseases
Demyelinating Diseases
Polyneuropathies
Nerve Compression Syndromes
Neurologic Manifestations
Neurotoxicity Syndromes
Cranial Nerve Diseases
Nervous System Diseases
Eye Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Signs and Symptoms

Poisoning
Substance-Related Disorders
Optic Atrophy
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Mitochondrial Diseases
Metabolic Diseases
Idebenone
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 21, 2013

Study to Assess Efficacy,Safety and Tolerability of Idebenone in the Treatment of Leber's Hereditary Optic Neuropathy (RHODOS)