Clinical trial NCT00747487: Study to Assess Efficacy,Safety and Tolerability of Idebenone in the Treatment of Leber's Hereditary Optic Neuropathy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leber's Hereditary Optic Neuropathy
Keywords: Leber
LHON
Leber's Hereditary Optic Neuropathy
Idebenone
Lead sponsor: Santhera Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2008-09-05
Enrollment: 85
Sex: ALL
Minimum age (years): 14
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: The study involves 6 clinic visits.

Eligibility 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

Primary outcomes:
measure: Best recovery of logMAR visual acuity between baseline and Week 24 in either right or left eye
timeFrame: 24 weeks
Secondary outcomes:
measure: Change in the patient's best logMAR visual acuity between baseline and week 24
timeFrame: 24 weeks
measure: Change in scotoma area in both eyes
timeFrame: Day -1, Week 4, Week 12, Week 24
measure: Change in optic nerve fibre layer thickness in both eyes
timeFrame: Day -1, Week 4, Week 12, Week 24
measure: Colour contrast sensitivity in both eyes (in a subset of patients)
timeFrame: Day -1, Week 4, Week 12, Week 24
measure: logMAR visual acuity as a continuous variable in both eyes
timeFrame: Screening, Day -1, Week 4, Week 12, Week 24, Week 28
measure: Clinical Global Impression of Change
timeFrame: Week 4, Week 12 and Week 24
measure: Change in Health-Related Quality of Life (HRQOL)
timeFrame: Day -1, Week 4, Week 12, Week 24
measure: Change in self-reported general energy levels
timeFrame: Day -1, Week 4, Week 12, Week 24, Week 28
measure: 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)
timeFrame: 24 weeks
measure: Plasma levels of idebenone matched to measures of efficacy and safety
timeFrame: 24 weeks
measure: • Best visual acuity at Week 24 (best eye at Week 24) compared to best visual acuity at Baseline (best eye at Baseline)
timeFrame: 24 weeks
measure: • Count of eyes/ patients for which the visual acuity improves between baseline and week 24
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Unité de recherche clinique Ophtalmologie- Hopital Notre-Dame
state: Quebec
city: Munich
country: Germany
facility: Klinikum der Universität München - Grosshadern, Neurologische Klinik und Poliklinik
city: Newcastle Upon Tyne
country: United Kingdom
facility: Clinical Research Facility, 4th Floor Leazes Wing, Royal Victoria Infirmary
Study officials:
affiliation: Clinical Research Facility, 4th Floor Leazes Wing, Royal Victoria Infirmary
name: Prof Patrick F Chinnery, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Klinikum der Universität München - Grosshadern, Neurologische Klinik und Poliklinik
name: Prof Thomas Klopstock, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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 Sep;134(Pt 9):2677-86. doi: 10.1093/brain/awr170. Epub 2011 Jul 25.
citation: Rudolph G, Dimitriadis K, Buchner 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. 2013 Mar;33(1):30-6. doi: 10.1097/WNO.0b013e318272c643.