The purpose of this survey is to collect visual acuity data from patients with LHON in order to establish the clinical course (natural history) and visual acuity outcomes in patients with a genetically confirmed diagnosis of LHON. In addition, this survey will generate data that will serve as comparator for the open-label study SNT-IV-006.

NCT02796274

Conditions

1. Leber's Hereditary Optic Neuropathy (LHON)

MeSH:Optic Nerve Diseases Optic Atrophy, Hereditary, Leber

HPO:Leber optic atrophy

Clinically Relevant Recovery (CRR) is defined as a VA improvement from off-chart (ETDRS) to 5 letters on-chart, or an on-chart improvement of 10 letters.. Inclusion Criteria: 1. age ≥ 12 years 2. the onset of symptoms is dated after 1999 and is well documented (at least month of onset of symptoms is known for each eye) 3. at least two VA assessments are available within 5 years of onset of symptoms and prior to idebenone use 4. have a genetic diagnosis for LHON for one of the following mitochondrial DNA (mtDNA) mutations: G11778A, G3460A, T14484C Exclusion Criteria: 1. any participation in an interventional clinical trial after the onset of symptoms 2. any other cause of visual impairment (e.g. --- G11778A ---

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.) during the data collection period Inclusion Criteria: 1. age ≥ 12 years 2. the onset of symptoms is dated after 1999 and is well documented (at least month of onset of symptoms is known for each eye) 3. at least two VA assessments are available within 5 years of onset of symptoms and prior to idebenone use 4. have a genetic diagnosis for LHON for one of the following mitochondrial DNA (mtDNA) mutations: G11778A, G3460A, T14484C Exclusion Criteria: 1. any participation in an interventional clinical trial after the onset of symptoms 2. any other cause of visual impairment (e.g. --- G11778A ---

Efficacy Study of Gene Therapy for The Treatment of Acute Leber's Hereditary Optic Neuropathy (LHON) onset within three months

NCT03428178

Conditions

1. Acute LHON
2. Onset Within Three Months
3. Onset Between 3 to 6 Months
4. Onset Between 6 to 12 Months
5. Onset Between 12 to 24 Months
6. Onset Between 24 to 60 Months
7. Onset Over 60 Months

Interventions

1. Drug: rAAV2-ND4

MeSH:Optic Atrophy, Hereditary, Leber

HPO:Leber optic atrophy

This is a multi - center , prospective study of 120 patients with the G11778A mutation in Mt-DNA.This clinical trial recruited 20 patients with the 11778 mutation of MT-DNA onset within three months,20 between 3 to 6 months,20 between 6 to 12 months,20 between 12 to 24 months,20 between 24 to 60 months,and 20 over 60 months.. --- G11778A ---

The goal of this clinical trial is to assess the long-term safety and efficacy of GS010, a gene therapy, and assess the quality of life in subjects with LHON due to the G11778A ND4 mitochondrial mutation and who were treated in the Rescue or Reverse studies.

NCT03406104

Conditions

1. Leber Hereditary Optic Neuropathy

Interventions

1. Genetic: GS010
2. Other: Sham

MeSH:Optic Nerve Diseases Optic Atrophy, Hereditary, Leber

HPO:Leber optic atrophy

RESCUE and REVERSE Long-term Follow-up The goal of this clinical trial is to assess the long-term safety and efficacy of GS010, a gene therapy, and assess the quality of life in subjects with LHON due to the G11778A ND4 mitochondrial mutation and who were treated in the Rescue or Reverse studies. --- G11778A ---

Expanded Access Use for a single patient of Bilateral Intravitreal Injection of GS010 in a Single Subject Affected with G11778A ND4 Leber Hereditary Optic Neuropathy

NCT03672968

Conditions

1. Leber Hereditary Optic Neuropathy (Optic, Atrophy, Hereditary, Leber)

Interventions

1. Genetic: GS010

MeSH:Optic Nerve Diseases Optic Atrophy, Hereditary, Leber Atrophy

HPO:Leber optic atrophy

EAP Single Patient: Safety of Bilateral Intravitreal Injection of GS010 in a Single Subject Affected With G11778A ND4 Leber Hereditary Optic Neuropathy. --- G11778A ---

EAP_GS010_single Patient Expanded Access Use for a single patient of Bilateral Intravitreal Injection of GS010 in a Single Subject Affected with G11778A ND4 Leber Hereditary Optic Neuropathy The EAP applies to patients not eligible to ongoing GS010 clinical trials. --- G11778A ---

Inclusion Criteria: - Presence of documented G11778A ND4 LHON-causing mutation - Signature of informed consent and assent from the parent/guardian and the patient. --- G11778A ---

- Presence of known/documented mutations, other than the G11778A ND4 LHON-causing mutation, which are known to cause pathology of the optic nerve, retina or afferent visual system. --- G11778A ---

The purpose of this study is to evaluate the safety and tolerability profile of ascending doses of GS010 in Leber Hereditary Optic Neuropathy (LHON) patients.

NCT02064569

Conditions

1. Leber Hereditary Optic Neuropathy

Interventions

1. Genetic: GS010

MeSH:Optic Nerve Diseases Optic Atrophy, Hereditary, Leber

HPO:Leber optic atrophy

Inclusion Criteria: Documented diagnosis of LHON based on a genetic test confirming the presence of the G11778A mutation in the mitochondrial ND4 Age 18 years old or older at the time of study entry (informed consent signature) Visual acuity ≤ 1/10 of the less functional eye Exclusion Criteria: Any known allergy or hypersensibility to one of the product used during the trial Contraindication to IVT surgery (anaemia Hb <8g/dl, severe cardiovascular disease, severe coagulopathy…) Disorder of the ocular humors and of the internal retina involving visual disability Glaucoma Presence of other pathology whose symptoms or associated treatments might affect the retina or the optic nerve Vascular retinal occlusion Narrow angle contra-indicating pupillary dilation Other cause of optic neuropathy (inflammatory conditions or exposure to toxins...) Patients presenting known mutation of other genes implicated in pathological retinal conditions Inclusion Criteria: Documented diagnosis of LHON based on a genetic test confirming the presence of the G11778A mutation in the mitochondrial ND4 Age 18 years old or older at the time of study entry (informed consent signature) Visual acuity ≤ 1/10 of the less functional eye Exclusion Criteria: Any known allergy or hypersensibility to one of the product used during the trial Contraindication to IVT surgery (anaemia Hb <8g/dl, severe cardiovascular disease, severe coagulopathy…) Disorder of the ocular humors and of the internal retina involving visual disability Glaucoma Presence of other pathology whose symptoms or associated treatments might affect the retina or the optic nerve Vascular retinal occlusion Narrow angle contra-indicating pupillary dilation Other cause of optic neuropathy (inflammatory conditions or exposure to toxins...) Patients presenting known mutation of other genes implicated in pathological retinal conditions Leber Hereditary Optic Neuropathy Optic Nerve Diseases Optic Atrophy, Hereditary, Leber null --- G11778A ---

Inclusion Criteria: Documented diagnosis of LHON based on a genetic test confirming the presence of the G11778A mutation in the mitochondrial ND4 Age 18 years old or older at the time of study entry (informed consent signature) Visual acuity ≤ 1/10 of the less functional eye Exclusion Criteria: Any known allergy or hypersensibility to one of the product used during the trial Contraindication to IVT surgery (anaemia Hb <8g/dl, severe cardiovascular disease, severe coagulopathy…) Disorder of the ocular humors and of the internal retina involving visual disability Glaucoma Presence of other pathology whose symptoms or associated treatments might affect the retina or the optic nerve Vascular retinal occlusion Narrow angle contra-indicating pupillary dilation Other cause of optic neuropathy (inflammatory conditions or exposure to toxins...) Patients presenting known mutation of other genes implicated in pathological retinal conditions Inclusion Criteria: Documented diagnosis of LHON based on a genetic test confirming the presence of the G11778A mutation in the mitochondrial ND4 Age 18 years old or older at the time of study entry (informed consent signature) Visual acuity ≤ 1/10 of the less functional eye Exclusion Criteria: Any known allergy or hypersensibility to one of the product used during the trial Contraindication to IVT surgery (anaemia Hb <8g/dl, severe cardiovascular disease, severe coagulopathy…) Disorder of the ocular humors and of the internal retina involving visual disability Glaucoma Presence of other pathology whose symptoms or associated treatments might affect the retina or the optic nerve Vascular retinal occlusion Narrow angle contra-indicating pupillary dilation Other cause of optic neuropathy (inflammatory conditions or exposure to toxins...) Patients presenting known mutation of other genes implicated in pathological retinal conditions Leber Hereditary Optic Neuropathy Optic Nerve Diseases Optic Atrophy, Hereditary, Leber null --- G11778A --- --- G11778A ---

Hypotheses: The primary hypothesis being tested is that there will be no toxicity resulting in loss of vision to no light perception in injected eyes.

NCT02161380

Conditions

1. Leber's Hereditary Optic Neuropathy

Interventions

1. Drug: injection of scAAV2-P1ND4v2 1.18x10e9 vg (Low),
2. Drug: injection of scAAV2-P1ND4v2 5.81 X10e9 vg (Med)
3. Drug: injection of scAAV2-P1ND4v2 2.4 X10e10vg (High)
4. Drug: injection of scAAV2-P1ND4v2 1.0 X10e11vg (Higher)

MeSH:Optic Nerve Diseases Optic Atrophy, Hereditary, Leber

HPO:Leber optic atrophy

An Open-label Dose Escalation Study of an Adeno-associated Virus Vector (scAAV2-P1ND4v2) for Gene Therapy of Leber's Hereditary Optic Neuropathy (LHON) Caused by the G11778A Mutation in Mitochondrial DNA. --- G11778A ---

Inclusion Criteria: 1. Age 15 or older; 2. Patients with LHON and the G11778A mitochondrial DNA mutation. --- G11778A ---

A previous CLIA certified genetic lab result showing the LHON G11778A mutation will be accepted for inclusion; 3. Ability to perform tests of visual and retinal function; 4. Ability to comply with research procedures; 5. Able and willing to provide informed consent before undergoing any study related procedures. --- G11778A ---

The goal of this clinical trial is to assess the effectiveness of GS010, a gene therapy, in improving the visual outcome in participants with Leber Hereditary Optic Neuropathy (LHON) due to the G11778A ND4 mitochondrial mutation when vision loss is present for more than six months and up to one year.

NCT02652780

Conditions

1. Optic, Atrophy, Hereditary, Leber

Interventions

1. Biological: GS010
2. Device: Sham Intravitreal Injection

MeSH:Atrophy

Randomized, Double-Masked, Sham-Controlled Clinical Trial to Evaluate the Efficacy of a Single Intravitreal Injection of GS010 in Subjects Affected for More Than 6 Months and To 12 Months by LHON Due to the G11778A Mutation in the ND4 Gene. --- G11778A ---

Efficacy Study of GS010 for Treatment of Vision Loss From 7 Months to 1 Year From Onset in LHON Due to the ND4 Mutation (REVERSE) The goal of this clinical trial is to assess the effectiveness of GS010, a gene therapy, in improving the visual outcome in participants with Leber Hereditary Optic Neuropathy (LHON) due to the G11778A ND4 mitochondrial mutation when vision loss is present for more than six months and up to one year. --- G11778A ---

Inclusion Criteria: Participants included in the study must satisfy all the following criteria at the Inclusion Visit (Visit 2). 1. Documented results of genotyping showing the presence of the G11778A mutation in the ND4 gene and the absence of the other primary LHON-associated mutations (ND1 or ND6) in the participant's mitochondrial DNA. 2. Review of all selection criteria to ensure continued compliance. --- G11778A ---

The goal of this clinical trial is to assess the effectiveness of GS010, a gene therapy, in improving the visual outcome in participants with Leber Hereditary Optic Neuropathy (LHON) due to the G11778A ND4 mitochondrial mutation when vision loss is present for six months or less.

NCT02652767

Conditions

1. Optic, Atrophy, Hereditary, Leber

Interventions

1. Biological: GS010
2. Device: Sham Intravitreal Injection

MeSH:Atrophy

A Randomized, Double-Masked, Sham-Controlled Clinical Trial to Evaluate the Efficacy of a Single Intravitreal Injection of GS010 in Subjects Affected for 6 Months or Less by LHON Due to the G11778A Mutation in the Mitochondrial ND4 Gene. --- G11778A ---

Efficacy Study of GS010 for the Treatment of Vision Loss up to 6 Months From Onset in LHON Due to the ND4 Mutation The goal of this clinical trial is to assess the effectiveness of GS010, a gene therapy, in improving the visual outcome in participants with Leber Hereditary Optic Neuropathy (LHON) due to the G11778A ND4 mitochondrial mutation when vision loss is present for six months or less. --- G11778A ---

Inclusion Criteria: Participants included in the study must satisfy all the following criteria at the Inclusion Visit (Visit 2). 1. Documented results of genotyping showing the presence of the G11778A mutation in the ND4 gene and the absence of the other primary Leber Hereditary Optical Neuropathy (LHON)-associated mutations (ND1 or ND6) in the participant's mitochondrial DNA. 2. Review of all selection criteria to ensure continued compliance. --- G11778A ---

This study is meant to evaluate the safety and efficacy of rAAV2-ND4 treatment for Leber hereditary optic neuropathy with the G11778A mutation in mitochondrial DNA.

NCT03153293

Conditions

1. Leber Hereditary Optic Neuropathy

Interventions

1. Drug: rAAV2-ND4

MeSH:Optic Nerve Diseases Optic Atrophy, Hereditary, Leber

HPO:Leber optic atrophy

A Single Intravitreal Injection of rAAV2-ND4 for the Treatment of Leber's Hereditary Optic Neuropathy This study is meant to evaluate the safety and efficacy of rAAV2-ND4 treatment for Leber hereditary optic neuropathy with the G11778A mutation in mitochondrial DNA. --- G11778A ---

This is an open-label, single-arm, multi-center study to further evaluate the safety and efficacy of rAAV-ND4 in the treatment of LHON patients with G11778A mutation. --- G11778A ---

The goal of this clinical trial is to assess the safety and efficacy of GS010, a gene therapy, in improving the retina functional & structural outcomes in subjects with LHON due to the G11778A ND4 mitochondrial mutation when vision loss duration is present up to one year.

NCT03293524

Conditions

1. Leber Hereditary Optic Neuropathy

Interventions

1. Genetic: GS010
2. Drug: Placebo

MeSH:Optic Nerve Diseases Optic Atrophy, Hereditary, Leber

HPO:Leber optic atrophy

Efficacy and Safety of Bilateral Intravitreal Injection of GS010: A Randomized, Double-Masked, Placebo-Controlled Trial in Subjects Affected With G11778A ND4 Leber Hereditary Optic Neuropathy for Up to One Year. --- G11778A ---

Efficacy & Safety Study of Bilateral IVT Injection of GS010 in LHON Subjects Due to the ND4 Mutation for up to 1 Year The goal of this clinical trial is to assess the safety and efficacy of GS010, a gene therapy, in improving the retina functional & structural outcomes in subjects with LHON due to the G11778A ND4 mitochondrial mutation when vision loss duration is present up to one year. --- G11778A ---

- Presence of known/documented mutations, other than the G11778A ND4 LHON-causing mutation, which are known to cause pathology of the optic nerve, retina or afferent visual system. --- G11778A ---

- Documented results of genotyping showing the presence of the G11778A mutation in the ND4 gene and the absence of the other primary LHON-associated mutations (ND1 or ND6) in the subject's mitochondrial DNA. --- G11778A ---

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.

NCT00747487

Conditions

1. Leber's Hereditary Optic Neuropathy

Interventions

1. Drug: Idebenone
2. Drug: Placebo

MeSH:Peripheral Nervous System Diseases Optic Nerve Diseases Optic Atrophy, Hereditary, Leber

HPO:Abnormal peripheral nervous system morphology Leber optic atrophy Peripheral neuropathy Polyneuropathy

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). --- G11778A ---

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 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). --- G11778A ---

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.

NCT02774005

Conditions

1. Leber's Hereditary Optic Neuropathy (LHON)

Interventions

1. Drug: Idebenone

MeSH:Optic Nerve Diseases Optic Atrophy, Hereditary, Leber

HPO:Leber optic atrophy

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 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. --- G11778A ---

8. Women who are pregnant or have a positive pregnancy test at Baseline visit 9. Women who are breastfeeding 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 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. --- G11778A ---