Current Neuro-Ophthalmology Trials

External Natural History Controlled, Open-Label Intervention Study to Assess the Efficacy and Safety of Long-Term Treatment with Idebenone (Raxone®) in Leber’s Hereditary Optic Neuropathy (LHON) (LEROS)
PI: Nancy Newman, MD
Coordinator: Deborah Gibbs, COMT, CCRC, CCRP
Status: Recruiting

General Summary:
The study will be an open-label interventional study requiring 125 patients enrolled ≤1 year after the onset of symptoms to complete the 12 month treatment period (for evaluation of the primary endpoint), and 125 patients enrolled >1 year after the onset of symptoms to complete the 12 month treatment period (for evaluation of the secondary endpoints in these patients).

This multinational study is conducted with one protocol for sites under the IND (U.S. sites) in compliance with the IND requirements contained in 21 CFR 312, and a different version of the protocol for foreign sites not under the IND. As the intent is to pool the data from U.S. and foreign sites, it is ensured, as required, that the protocol versions are very similar or identical.

Patient eligibility for enrollment will be determined during the Baseline (Visit 1). Beginning at Baseline (Visit 1), the patient will receive study medication to take at home and will undergo regular assessments in the clinic throughout the study period until Visit 8 (Month 24) at which time the study medication is withdrawn. For all patients, there will be a final follow-up 28-35 days after study medication withdrawal. Patients enrolled in the study will commence study medication intake on the first day after the Baseline visit.

Clinical Summary:
Patients will be enrolled to receive 900 mg idebenone (2 tablets 3 times daily with meals) for 24 months. Starting with Baseline/Visit 1 sufficient study medication will be dispensed to last until the next visit. The patient will take the first dose of study medication on Day 1, the day of the Baseline Visit (or as instructed by the site investigator / study nurse).

The duration of study participation for each individual patient will be approximately 25 months and comprise 9 study visits (V1-V9). Before any study-specific procedures are undertaken, the patient (and parent/legal guardian if required) will have been thoroughly informed by the investigator of the purpose of the study, the relevant procedures and of patient rights and responsibilities. Patient information will be distributed in writing and signatures of consent obtained on the consent form. (See also Section 10.3).

Patient enrolled in the study will receive study medication at Baseline/Visit 1; the first study medication intake is on the day of the Baseline/Visit 1 (or as instructed by the site investigator / study nurse). During the 24 month treatment period, visits take place at Month 1, Month 3, Month 6, Month 9, Month 12, Month 18 and Month 24. Visit 8 (Month 24) is the endpoint of treatment. Visit 9 is a follow-up, 28-35 days after study medication discontinuation. Physical examination and measurement of vital signs will be undertaken at Baseline/Visit 1 and then at Visit 4/Month 6, Visit 6/Month 12, Visit 7/Month 18 and Visit 8/Month 24. Safety blood and urine and safety assessments will be done at each visit.

A urine or serum pregnancy test will be performed for WCBP when clinically indicated. Assessment of VA (assessed by ETDRS charts and reported in logMAR value) will be done at every visit.

During the Baseline visit the diagnosis of LHON will be confirmed and other eye diseases excluded. This will require fundus exam with dilated pupils to be performed at the Baseline visit and every 12 months thereafter. Blood sample will be taken for the genetic analysis, if the genetic diagnosis of the patient is not confirmed at the Baseline visit. The report from the genetic analysis should be on file prior to Visit 4.
Should the genetic diagnosis reveal that a patient does not harbour a LHON-specific mtDNA mutation, the patient will be withdrawn from the study.

It should be noted however that the VA outcomes for patients carrying one of the three major LHON-specific mtDNA mutations (G3460A, G11778A or T14484A) will be used in the primary analyses.

Inclusion Criteria:
The following criteria should be assessed during Baseline Visit. 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.

Exclusion Criteria:
The following criteria should be checked during Baseline Visit. 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: 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

Contact: Deborah Gibbs; (404) 778-5815;
Posted: 01-24-2018

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