There are 12 clinical trials
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.
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 ---
Description: In eyes with a VA assessment made ≤1 year after the onset of symptoms: Proportion of eyes with clinically relevant recovery of VA from Baseline or in which Baseline VA better than 1.0 logarithm of the minimal angle of resolution (logMAR) was maintained at 12 months (primary time point)
Measure: Proportion of eyes with clinically relevant recovery or clinically relevant stabilization of VA Time: 12 monthsEfficacy Study of Gene Therapy for The Treatment of Acute Leber's Hereditary Optic Neuropathy (LHON) onset within three months
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 ---
Description: The Best Corrected Visual Acuity
Measure: BCVA Time: Change from Baseline at 12 monthsDescription: Visual Field index
Measure: Computerized Visual Field Time: Change from Baseline at 12 monthsDescription: Mean Defect
Measure: Computerized Visual Field Time: Change from Baseline at 12 monthsDescription: visual evoked potential
Measure: VEP Time: Change from Baseline at 12 monthsDescription: retinal nerve fiber layer
Measure: RNFL Time: Change from Baseline at 12 monthsDescription: Before and after the treatment,Liver function in plasma will be checked.
Measure: Liver function in plasma Time: Before treatment and in the first ,third,sixth,twelfth month after the treatmentDescription: Before and after the treatment,kidney function in plasma will be checked.
Measure: kidney function in plasma Time: Before treatment and in the first ,third,sixth,twelfth month after the treatmentThe 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.
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 ---
Description: AEs or SAEs (ocular or systemic) related to IMP or administration procedure, as judged by the Investigator, reported during the long-term follow-up visits (2, 2.5, 3, 4, and 5 years) from the period of 96 weeks up to 5 years post-treatment and summarized descriptively by type, frequency (number, percentage), severity, causal relationship, and seriousness
Measure: Adverse events (AEs) or serious adverse events (SAEs) (ocular or systemic) Time: Up to 5-Year post-treatmentDescription: Change in best BCVA reported with LogMAR
Measure: Best-Corrected Visual Acuity (BCVA) reported with LogMAR Time: Up to 5-Year post-treatmentDescription: Change of parameters measured with HVF 30-2
Measure: HumphreyTM visual field (HVF) 30-2 parameters Time: Up to 5-Year post-treatmentDescription: Change of parameters measured with SD-OCT
Measure: Spectral domain optical coherence tomography (SD-OCT) parameters Time: Up to 5-Year post-treatmentDescription: Response status of eyes treated with GS010 IVT injection compared to eyes treated with sham IVT injection (An improvement of at least 15 ETDRS letters/Eyes that lose less than the 15 ETDRS letters)
Measure: Responder Analysis Time: Up to 5-Year post-treatmentDescription: Time course of the response in eyes treated with GS010 IVT injection compared to eyes treated with sham IVT injection, for the BCVA reported with LogMAR, for parameters measured with HVF 30-2 and SD-OCT
Measure: Time course of the response Time: Up to 5-Year post-treatmentDescription: Visual improvement as measured by LogMAR by analysis of covariance (ANCOVA)
Measure: Visual improvement Time: Up to 5-Year post-treatmentDescription: Change of GCL thickness/volume and topographical map and other parameters measured by SD-OCT using a mixed model of ANCOVA
Measure: Change of ganglion cell layer (GCL) thickness/volume and topographical map and other parameters measured by SD-OCT Time: Up to 5-Year post-treatmentDescription: QOL as measured with VFQ-25 subject-rated instrument
Measure: Quality of Life: Visual Functioning Questionnaire 25 (VFQ-25) Time: Up to 5-Year post-treatmentDescription: QOL as measured with SF-36v2 subject-rated instrument
Measure: Quality of Life: 36-Item Short Form Health Survey, version 2 (SF-36-v2) Time: Up to 5-Year post-treatmentExpanded Access Use for a single patient of Bilateral Intravitreal Injection of GS010 in a Single Subject Affected with G11778A ND4 Leber Hereditary Optic Neuropathy
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.
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 Neuritis 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 Neuritis 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.
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 ---
Description: Incidence of local and general adverse events and Serious Adverse Events
Measure: Assessment of Primary Endpoint - Toxicity Time: 1 yearThe goal of this clinical trial is to assess the effectiveness of GS010, a gene therapy, in improving the visual outcome in patients with LHON due to the G11778A ND4 mitochondrial mutation when vision loss is present for more than six months and up to one year.
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 The goal of this clinical trial is to assess the effectiveness of GS010, a gene therapy, in improving the visual outcome in patients with 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: Subjects 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 subject's mitochondrial DNA. 2. Review of all selection criteria to ensure continued compliance. --- G11778A ---
Description: The primary endpoint will be the ETDRS visual acuity (quantitative score) at Week 48 after intravitreal injection. The subjects' LogMAR scores, which are derived from the number of letters they read on the ETDRS chart, will be used for statistical analysis purposes. The change from baseline in each eye will be the primary response of interest.
Measure: ETDRS visual acuity, utilizing derived LogMAR acuity Time: 48 weeks after GS010/sham injectionDescription: ETDRS visual acuity (quantitative score) over the follow-up period and at Week 96 after intravitreal injection. Change from baseline of the LogMAR scores will be used for statistical analysis purposes.
Measure: ETDRS visual acuity, utilizing derived LogMAR acuity Time: 96 weeks after GS010/sham injectionDescription: Response status to treatment at Week 48 and 96 after intravitreal injection will be determined. Responder will be defined by an improvement of at least 15 letters in the visual acuity score obtained with ETDRS or being greater than a Snellen acuity equivalent of 20/200. The number of GS010-treated eyes that qualify as responders will be compared to the number of sham-treated eyes that qualify as responders.
Measure: Responder Analysis: Improvement from Baseline by 15 ETDRS letters or having Visual Acuity >20/200 at 48 and 96 weeks Time: 48 and 96 weeks after GS010/sham injectionDescription: Measure of parameters of high resolution SD-OCT of the posterior pole and optic nerve at Week 48 and Week 96.Total average and quadrant thickness of the RNFL will be evaluated. The various layers of the retina, including the retinal ganglion cell layer and inner plexiform layer, will be analyzed and the thickness/volume will be evaluated.
Measure: High Resolution Spectral Domain Optical Coherence Tomography to measure the optic nerve retinal nerve fiber layer (RNFL) thickness and the thickness/volume of the retinal layers of the macula Time: 48 and 96 weeks after GS010/sham injectionDescription: Measure of the standardized automated visual fields obtained with HVF Analyzer II. Mean Deviation (MD) in decibels of sensitivity will be used at Week 48 and Week 96.
Measure: Humphrey Visual Field 30-2 Time: 48 and 96 weeks after GS010/sham injectionDescription: Measure of contrast sensitivity with the Pelli-Robson chart at Week 48 and Week 96.
Measure: Pelli-Robson Contrast Sensitivity Time: 48 and 96 weeks after GS010/sham injectionDescription: Measure of color vision with the Farnsworth-Munsell 100 Hue color vision test at Week 48 and Week 96.
Measure: Farnsworth-Munsell Color 100 Hue Vision Test Time: 48 and 96 weeks after GS010/sham injectionDescription: Adverse events (AEs) and serious adverse events (SAEs), including those that are treatment-emergent and non-treatment-emergent, throughout the study period and at each study visit. Incidence and severity of systemic and local (ocular) AEs and SAEs will be determined at each clinical site and for the entire study cohort.
Measure: Adverse Events and Serious Adverse Events Time: Continuous over 96 week study periodDescription: Results of immune response evaluations: Time course of neutralizing antibodies against AAV2 vector and cellular immune response against AAV2 vector and ND4 protein.
Measure: Immune Responses Time: 96 week study periodDescription: Blood bio-dissemination two weeks after injection of GS010. The presence of AAV2 vector DNA in the blood of subjects will be tested for and quantified utilizing quantitative PCR.
Measure: Blood Bio-dissemination of AAV2 Vector DNA Time: Two weeks post GS010 administrationDescription: The better seeing-eye of each patient will be determined at visit 1, prior to randomization. A pre-determined algorithm of criteria in a hierarchy will be used to determine the better seeing-eye based on vision testing results (e.g. visual acuity, SD-OCT, contrast sensitivity). A minimization method will be employed in the randomization process to ensure, as best as possible, an even distribution of better seeing-eyes to receipt of GS010 and sham. Better-seeing eyes that received GS010 will be compared to better-seeing eyes that received sham. A similar analysis will be done for worse-seeing eyes.
Measure: Better-Seeing Eye Comparison Time: 48 and 96 weeks after GS010/sham injectionDescription: Visual Functioning Questionnaire-25.
Measure: Quality of Life: Visual Functioning Questionnaire-25 Time: 48 and 96 weeks after GS010/sham injectionDescription: 36-Item Short Form Health Survey, version 2 Questionnaire.
Measure: Quality of Life: 36-Item Short Form Health Survey, version 2 Questionnaire Time: 48 and 96 weeks after GS010/sham injectionThe goal of this clinical trial is to assess the effectiveness of GS010, a gene therapy, in improving the visual outcome in patients with LHON due to the G11778A ND4 mitochondrial mutation when vision loss is present for six months or less.
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 patients with LHON due to the G11778A ND4 mitochondrial mutation when vision loss is present for six months or less. --- G11778A ---
Inclusion Criteria: Subjects 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 subject's mitochondrial DNA. 2. Review of all selection criteria to ensure continued compliance. --- G11778A ---
Description: The primary endpoint will be the ETDRS visual acuity (quantitative score) at Week 48 after intravitreal injection. The subjects' LogMAR scores, which are derived from the number of letters they read on the ETDRS chart, will be used for statistical analysis purposes. The change from baseline in each eye will be the primary response of interest.
Measure: ETDRS visual acuity, utilizing derived LogMAR acuity Time: 48 weeks after GS010/sham injectionDescription: ETDRS visual acuity (quantitative score) over the follow-up period and at Week 96 after intravitreal injection. Change from baseline of the LogMAR scores will be used for statistical analysis purposes.
Measure: ETDRS visual acuity, utilizing derived LogMAR acuity Time: 96 weeks after GS010/sham injectionDescription: Response status to treatment at Week 48 and 96 after intravitreal injection will be determined. Responder will be defined by an improvement of at least 15 letters in the visual acuity score obtained with ETDRS or being greater than a Snellen acuity equivalent of 20/200. The number of GS010-treated eyes that qualify as responders will be compared to the number of sham-treated eyes that qualify as responders.
Measure: Responder Analysis: Improvement from Baseline by 15 ETDRS letters or having Visual Acuity >20/200 at 48 and 96 weeks Time: 48 and 96 weeks after GS010/sham injectionDescription: Measure of parameters of high resolution SD-OCT of the posterior pole and optic nerve at Week 48 and Week 96.Total average and quadrant thickness of the RNFL will be evaluated. The various layers of the retina, including the retinal ganglion cell layer and inner plexiform layer, will be analyzed and the thickness/volume will be evaluated.
Measure: High Resolution Spectral Domain Optical Coherence Tomography to measure the optic nerve retinal nerve fiber layer (RNFL) thickness and the thickness/volume of the retinal layers of the macula Time: 48 and 96 weeks after GS010/sham injectionDescription: Measure of the standardized automated visual fields obtained with HVF Analyzer II. Mean Deviation (MD) in decibels of sensitivity will be used at Week 48 and Week 96.
Measure: Humphrey Visual Field 30-2 Time: 48 and 96 weeks after GS010/sham injectionDescription: Measure of contrast sensitivity with the Pelli-Robson chart at Week 48 and Week 96.
Measure: Pelli-Robson Contrast Sensitivity Time: 48 and 96 weeks after GS010/sham injectionDescription: Measure of color vision with the Farnsworth-Munsell 100 Hue color vision test at Week 48 and Week 96.
Measure: Farnsworth-Munsell Color 100 Hue Vision Test Time: 48 and 96 weeks after GS010/sham injectionDescription: Adverse events (AEs) and serious adverse events (SAEs), including those that are treatment-emergent and non-treatment-emergent, throughout the study period and at each study visit. Incidence and severity of systemic and local (ocular) AEs and SAEs will be determined at each clinical site and for the entire study cohort.
Measure: Adverse Events and Serious Adverse Events Time: Continuous over 96 week study periodDescription: Results of immune response evaluations: Time course of neutralizing antibodies against AAV2 vector and cellular immune response against AAV2 vector and ND4 protein
Measure: Immune Responses Time: 96 week study periodDescription: Blood bio-dissemination two weeks after injection of GS010. The presence of AAV2 vector DNA in the blood of subjects will be tested for and quantified utilizing quantitative PCR.
Measure: Blood Bio-dissemination of AAV2 Vector DNA Time: Two weeks post GS010 administrationDescription: The better seeing-eye of each patient will be determined at visit 1, prior to randomization. A pre-determined algorithm of criteria in a hierarchy will be used to determine the better seeing-eye based on vision testing results (e.g. visual acuity, SD-OCT, contrast sensitivity). A minimization method will be employed in the randomization process to ensure, as best as possible, an even distribution of better seeing-eyes to receipt of GS010 and sham. Better-seeing eyes that received GS010 will be compared to better-seeing eyes that received sham. A similar analysis will be done for worse-seeing eyes.
Measure: Better-Seeing Eye Comparison Time: 48 and 96 weeks after GS010/sham injectionDescription: Visual Functioning Questionnaire-25 quality of life scale.
Measure: Quality of Life: Visual Functioning Questionnaire-25 Time: 48 and 96 weeks after GS010/sham injectionDescription: 36-Item Short Form Health Survey, version 2 Questionnaire quality of life scale.
Measure: Quality of Life:36-Item Short Form Health Survey, version 2 Questionnaire Time: 48 and 96 weeks after GS010/sham injectionThis 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.
Safety and Efficacy Study of Gene Therapy 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 a multi - center , prospective study of 142 patients with the G11778A mutation in Mt-DNA . --- G11778A ---
Description: The Best Corrected Visual Acuity
Measure: BCVA Time: Change from Baseline at 12 months .Description: visual evoked potential
Measure: VEP Time: Change from Baseline at 12 months .Description: retinal nerve fiber layer
Measure: RNFL Time: Change from Baseline at 12 months .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.
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 ---
Description: The primary endpoint will be the BCVA reported with LogMAR at 1-Year post-treatment in second affected/not yet affected eyes. The change from baseline in second affected/not yet affected eyes receiving GS010 and placebo will be the primary response of interest. LogMAR BCVA will be used for statistical purposes.
Measure: Best-Corrected Visual Acuity (BCVA) reported using Log of the Minimal Angle of Resolution (LogMAR) - 1 year Time: at 1-Year post baseline treatmentDescription: LogMAR BCVA at each timepoint of the follow-up period and at 2-years post-treatment, for second affected/not yet affected eyes receiving GS010 versus placebo and also for first affected eyes receiving GS010. The change from baseline of the LogMAR BCVA will be used for statistical analyses.
Measure: Best-Corrected Visual Acuity (BCVA) reported with LogMAR - 2 years Time: at 2-Years post baseline treatmentDescription: Response status over time and at 1 and 2-years post baseline treatment. Response status will be assessed for second affected/not yet affected eyes receiving GS010 versus placebo and also for first affected eyes receiving GS010. Definitions of responder eyes include: Eyes whose LogMAR BCVA improves (i.e. decreases) by ≥ 0.3 LogMAR (equivalent to a gain of ≥ 15 ETDRS letters) compared to baseline. Eyes whose LogMAR BCVA does not increase (i.e. worsen) by ≥ 0.3 LogMAR (equivalent to eye that lose ≤ 15 ETDRS letters) compared to baseline. Eyes whose LogMAR visual acuity is < 1.0 (i.e. better than LogMAR 1.0, equivalent to better than Snellen acuity of 20/200).
Measure: Responder Analysis Time: at 1-Year and 2-Years post baseline treatmentDescription: Parameters measured with SD-OCT over time and at 1 and 2-years post baseline treatment. The change from baseline will be the response. Analysis will be performed mainly for second affected/not yet affected eyes treated with GS010 versus placebo and also for first affected eyes receiving GS010 as well
Measure: Spectral-Domain - Optical Coherence Tomography (SD-OCT) parameter Time: at 1-Year and 2-Years post baseline treatmentDescription: Parameters measured with HVF 30-2 over time and at 1 and 2-years post baseline treatment. The change from baseline will be the response. Analysis will be performed mainly for second affected/not yet affected eyes treated with GS010 versus placebo and also for first affected eyes receiving GS010 as well
Measure: Humphrey Visual Field (HVF) parameter Time: at 1-Year and 2-Years post baseline treatmentDescription: Parameters measured with Pelli Robson Low Vision Contrast Sensitivity over time and at 1 and 2-years post baseline treatment. The change from baseline will be the response. Analysis will be performed mainly for second affected/not yet affected eyes treated with GS010 versus placebo and also for first affected eyes receiving GS010 as well
Measure: Pelli Robson Low Vision Contrast Sensitivity parameter Time: at 1-Year and 2-Years post baseline treatmentDescription: Visual Functioning Questionnaire-25 at 1 and 2-years post-treatment
Measure: Quality of Life: Visual Functioning Questionnaire-25 Time: at 1-Year and 2-Years post baseline treatmentDescription: 36-Item Short Form Health Survey, version 2 Questionnaire at 1 and 2-years post-treatment.
Measure: Quality of Life: 36-Item Short Form Health Survey, version 2 Questionnaire Time: at 1-Year and 2-Years post baseline treatmentDescription: Adverse events (AEs) and serious adverse events (SAEs), including those that are treatment-emergent and non-treatment-emergent, throughout the study period and at each study visit. Incidence and severity of systemic and local (ocular) AEs and SAEs will be determined at each clinical site and for the entire study cohort.
Measure: Adverse events (AEs) and serious adverse events (SAEs) Time: up to 2-Years post baseline treatmentDescription: Results of physical examinations
Measure: Physical examinations Time: At 2-Years post baseline treatmentDescription: Results of Electrocardiograms (ECGs)
Measure: Electrocardiograms Time: At 2-Years post baseline treatmentDescription: Results of laboratory tests from blood collection
Measure: Laboratory results Time: At 2-Years post baseline treatmentDescription: Results of immune response evaluations Time course of the humoral immune response measured with Neutralizing Antibodies (Nab) against Adeno-associated virus vector 2 (AAV2) Time course of the cellular immune response against AAV2
Measure: Immune response evaluations Time: Up to 2-Years post baseline treatmentDescription: Results of bio-dissemination testing up to 4-weeks post-treatment
Measure: Blood Bio-dissemination of AAV2 Vector DNA Time: up to 4 weeks post-treatmentThis 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.
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.
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 ---
Description: Proportion 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
Measure: Proportion of eyes with clinically relevant recovery of visual acuity from Baseline Time: 12 months