Leber’s Hereditary Optic Neuropathy / LHON is a maternally inherited loss of vision due to atrophy of the optic nerve. It typically presents in young adults, mostly men, as painless acute or subacute visual failure of both eyes in quick succession. The estimated prevalence is approximately 2.2 per 100,000 (Mascialino et al., 2012) and LHON is thus an Orphan Disease according to EU and US criteria. MedDRA version: 20.1 Level: LLT Classification code 10062951 Term: Leber's hereditary optic atroph
Conditions
Interventions
Trade Name: Raxone
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: idebenone
CAS Number: 58186-27-9
Other descriptive name: IDEBENONE
Concentration unit: mg milligram(s)
Concentration typ
Sponsors
Santhera Pharmaceuticals (Switzerland) Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The following criteria should be assessed during Baseline Visit before randomization. If any does not apply, the patient must not be included in the study: 1. Impaired visual acuity in affected eyes due to LHON 2. No explanation for visual loss besides LHON 3. Age=12 years 4. Onset of symptoms =5 years prior to Baseline 5. Confirmation of either G11778A, G3460A or T14484C LHON mtDNA (for the ITT population, not required for enrolment) 6. Written informed consent obtained from the patient 7. Ability and willingness to comply with study procedures and visits 8. 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 Are the trial subjects under 18? yes Number of subjects for this age range: 30 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 123 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 7
Exclusion criteria
Exclusion criteria: The following criteria should be checked during Baseline Visit before randomization. If any applies, the patient must not be included in the study: 1. Patient has provided natural history data to the Case Record Survey (SNT-CRS-002) 2. Any previous use of idebenone 3. 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.) 4. Known history of clinically significant elevations (greater than 3 times the upper limit of normal) of AST, ALT or creatinine 5. 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 6. Participation in another clinical trial of any investigational drug within 3 months prior to Baseline 7. 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). 8. Women who are pregnant or have a positive pregnancy test at Baseline visit 9. Women who are breastfeeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess efficacy of Raxone® in the promotion of recovery or stabilization of visual acuity in patients treated with Raxone® =1 year after the onset of symptoms, compared to an external natural history control group of idebenone naïve patients;Secondary Objective: • To assess efficacy of Raxone® in the promotion of recovery or stabilization of vision in LHON patients treated with Raxone® >1 year after the onset of symptoms, compared to an external natural history control group of idebenone naïve patients • To compare the promotion of recovery or stabilization of visual acuity in LHON patients treated with Raxone® =1 and >1 year after the onset of symptoms • To assess the influence of mutation on the promotion of recovery or stabilization of visual acuity in LHON patients treated with Raxone® • To assess the influence of time since onset of symptoms prior to the initiation of treatment with Raxone® on the promotion of recovery or stabilization of visual acuity in LHON patients • To assess the influence of duration of treatment with Raxone® on changes in visual acuity in LHON patients • To assess safety of long-term treatment of LHON patients with Raxone® ;Primary end point(s): Proportion of eyes with clinically relevant recovery of 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 Clinically Relevant Recovery (CRR) is defined as a change from “off-chart” visual acuity (VA) to at least 1.6 logMAR value or an improvement of at least 0.2 logMAR value within “on-chart”. ;Timepoint(s) of evaluation of this end point: see E.5.1 text | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Components of the primary endpoint: - Proportion of eyes with CRR of VA from Baseline at Month 12 compared to matching external natural history control group - Proportion of eyes in which Baseline VA better than 1.0 logMAR was maintained at Month 12 compared to matching external natural history control group • Proportion of eyes in patients treated with Raxone® >1 year after the onset of symptoms with CRR of VA from Baseline or in which Baseline VA better than 1.0 logMAR was maintained at Month 12 compared to external natural history control group, in all patients and classified by mutation • Proportion of eyes and patients treated with Raxone® =1 year after the onset of symptoms with CRR of VA from Baseline or in which Baseline visual acuity better than 1.0 logMAR was maintained following 6, 18 and 24 months of treatment with Raxone® compared to matching external natural history control group, in all patients and classified by mutation • Proportion of eyes/patients treated with Raxone® =1 year or >1 year after the onset of symptoms with “Off-chart” VA at Baseline in whom VA improves to better than 1.60 logMAR by Month 6, 12, 18 and 24 • Proportion of eyes/patients treated with Raxone® =1 year or >1 year after the onset of symptoms with VA in the categories of better than 1.0 logMAR, 1.0 to 1.68 logMAR and above 1.68 logMAR at each assessment time point up to Month 24 • Safety as assessed by AE count and laboratory analyses during the study;Timepoint(s) of evaluation of this end point: see E.5.2 text | — |
Countries
Austria, Belgium, Bulgaria, Germany, Italy, Poland, Portugal, Spain, United Kingdom, United States
Contacts
Public ContactRegulatory Affairs Manager
Santhera Pharmaceuticals (Switzerland) Ltd
Outcome results
None listed