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

Phase 4

Completed

• Conditions: Leber's Hereditary Optic Neuropathy (LHON)
• Interventions: Drug: Idebenone

• Registration Number: NCT02774005
• Lead Sponsor: Santhera Pharmaceuticals

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-05
• Study First Submitted: 2016-05-12
• Study First Submitted QC: 2016-05-13
• Study First Posted: 2016-05-16
• Primary Completion: 2021-03-29
• Study Completion: 2021-03-29
• Results First Submitted: 2022-08-15
• Status Verified: 2023-03
• Results First Submitted QC: 2023-03-31
• Last Update Submitted: 2023-03-31
• Results First Posted: 2023-04-21
• Last Update Posted: 2023-04-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 199

Inclusion Criteria

1. Impaired visual acuity in affected eyes due to LHON
2. No explanation for visual loss besides LHON
3. Age more or equal 12 years
4. Onset of symptoms ≤5 years of Baseline
5. Confirmation of either G11778A, G3460A or T14484C LHON mtDNA (for the Intent-to Treat (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

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 aspartate aminotransferase (AST), alanine transaminase (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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Raxone	Idebenone	-

Primary Outcome Measures

Name	Time	Method
Proportion (Number) of Eyes With Clinically Relevant Recovery of Visual Acuity From Baseline	12 months	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

Secondary Outcome Measures

Name	Time	Method
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	12 months	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
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	12 months	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

Trial Locations

Locations (29)

University Hospital of Wales; 🇬🇧 Cardiff, United Kingdom

Institut Catala de Retina; 🇪🇸 Barcelona, Spain

Hospital Universitario Ramon y Cajal; 🇪🇸 Madrid, Spain

Moorfields Eye Hospital; 🇬🇧 London, United Kingdom

Queen's Hospital; 🇬🇧 Romford, United Kingdom

Retinal Consultants of Arizona; 🇺🇸 Phoenix, Arizona, United States

University of Colorado Health Eye Center; 🇺🇸 Aurora, Colorado, United States

Stanford Byers Eye Institute; 🇺🇸 Stanford, California, United States

CHU Saint-Pierre; 🇧🇪 Brussels, Belgium

New York Eye and Ear Infirmary; 🇺🇸 New York, New York, United States

University of Virginia; 🇺🇸 Charlottesville, Virginia, United States

Washington University; 🇺🇸 Saint Louis, Missouri, United States

Manchester Royal Eye Hospital; 🇬🇧 Manchester, United Kingdom

Cliniques Universitaire Saint-Luc; 🇧🇪 Brussels, Belgium

SPZOZ Spital Uniwersytecki w Krakowie, Oddzial Kliniczny Okulistyki i Onkologii Okulistycznej; 🇵🇱 Krakow, Poland

Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego; 🇵🇱 Poznań, Poland

C. H. U. Sart Tilman; 🇧🇪 Liège, Belgium

Università di Bologna-Clinica Neurologica-Dipartimento di Scienze Neurologiche; 🇮🇹 Bologna, Italy

Uniwersytecki Szpital Kliniczny; 🇵🇱 Wrocław, Poland

Centro Hospitalar de São João, EPE; 🇵🇹 Porto, Portugal

Bethesda Neurology, LLC; 🇺🇸 Bethesda, Maryland, United States

Friedrich-Baur-Institut; 🇩🇪 Muenchen, Germany

Samodzielny Publiczny Szpital Kliniczny Nr 2 PUM w Szczecinie; 🇵🇱 Szczecin, Poland

AKH - Medizinische Universitaet Wien; 🇦🇹 Wien, Austria

UZ Leuven - Campus Sint-Rafaël; 🇧🇪 Leuven, Belgium

UMHAT "Alexandrovska" EAD; 🇧🇬 Sofia, Bulgaria

Samodzielny Publiczny Kliniczny Szpital Okulistyczny; 🇵🇱 Warszawa, Poland

Palo Alto Medical Foundation; 🇺🇸 Palo Alto, California, United States

Emory University Hospital; 🇺🇸 Atlanta, Georgia, United States