Study to Assess the Efficacy and Safety of Raxone in LHON Patients

Study Overview
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Brief Summary
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LEROS is an open-label interventional Phase IV study, designed to further assess the efficacy and safety of Raxone® in the long-term treatment of LHON patients.

Official Title
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External Natural History Controlled, Open-Label Intervention Study to Assess the Efficacy and Safety of Long-Term Treatment With Raxone® in Leber's Hereditary Optic Neuropathy (LHON)

Conditions
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Leber's Hereditary Optic Neuropathy (LHON)

Intervention / Treatment
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* Drug: Idebenone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Impaired visual acuity in affected eyes due to LHON No explanation for visual loss besides LHON Age more or equal 12 years Onset of symptoms ≤5 years of Baseline Confirmation of either G11778A, G3460A or T14484C LHON mtDNA (for the Intent-to Treat (ITT) population, not required for enrolment) Written informed consent obtained from the patient Ability and willingness to comply with study procedures and visits Women of Childbearing Potential (WCBP) who have a negative urine or serum pregnancy test at Baseline visit and who are willing to use a highly effective contraceptive measure and maintain it until treatment discontinuation. Exclusion Criteria: Patient has provided natural history data to the Case Record Survey (SNT-CRS-002) Any previous use of idebenone Any other cause of visual impairment (e.g. glaucoma, diabetic retinopathy, AIDS related visual impairment, cataract, macular degeneration, etc.) or any active ocular disorder (uveitis, infections, inflammatory retinal disease, thyroid eye disease, etc.) Known history of clinically significant elevations (greater than 3 times the upper limit of normal) of aspartate aminotransferase (AST), alanine transaminase (ALT) or creatinine Patient has a condition or is in a situation which, in an investigator's opinion may put the patient at significant risk, may confound study results or may interfere significantly with the patient's participation in the study Participation in another clinical trial of any investigational drug within 3 months prior to Baseline Hypersensitivity to the active substance or to any of the following excipients (as listed in section 6.1 of Raxone SmPC): Lactose monohydrate, Microcrystalline cellulose, Croscarmellose sodium, Povidone K25, Magnesium stearate, Colloidal silica, Macrogol 3350, Poly(vinyl alcohol), Talc, Titanium dioxide, Sunset yellow FCF (E110). Women who are pregnant or have a positive pregnancy test at Baseline visit Women who are breastfeeding

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Raxone<br> | Drug: Idebenone<br> <br> * Other names: Raxone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion (Number) of Eyes With Clinically Relevant Recovery of Visual Acuity From Baseline | Proportion (number) of eyes with clinically relevant recovery of visual acuity (VA) from Baseline or in which Baseline VA better than 1.0 logMAR was maintained at Month 12 in patients treated with Raxone® ≤1 year after the onset of symptoms, compared to matching external natural history control group | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Components of the Primary Endpoint: Proportion of Eyes With Clinically Relevant Recovery (CRR) of VA From Baseline at Month 12 Compared to Matching External National History (NH) Control Group | CRR is defined as: Improvement from off-chart (the equivalent of Counting fingers, Hand motion, Light perception or No light perception) Visual Acuity to at least 1.6 logMAR value, OR Improvement of at least 0.2 logMAR value within on-chart Visual Acuity A patient had a CRR if at least one eye had CRR. logMAR = Logarithm of the minimum angle of resolution | 12 months | 
| Components of the Primary Endpoint: Proportion of Eyes in Which Baseline Visual Acuity (VA) Better Than 1.0 logMAR Was Maintained at Month 12 (Clinically Relevant Stabilization) Compared to Matching External NH Control Group | For proportion of eyes in which baseline VA better than 1.0 logMAR was maintained at Month 12 (CRS) compared to matching external NH control group only patients having VA < 1.0 at baseline are taking into account. Clinically relevant stabilization (CRS) was defined as maintenance of VA <1.0 logMAR in eyes with VA <1.0 logMAR at Baseline. A patient had a CRS if at least one eye had CRS. logMAR = Logarithm of the minimum angle of resolution | 12 months |