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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-001266-26 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GS010-treated Eyes | Experimental | Each participant will have one eye randomly selected to receive a single injection of GS010 and the other eye will receive a sham injection. GS010-treated Eyes: GS010 is a recombinant adeno-associated viral vector serotype 2 (rAAV2/2) containing the wild-type ND4 gene (rAAV2/2-ND4). Participants will receive a single dose of GS010 in one of their randomly selected eyes, via intravitreal injection containing 9E10 viral genomes in 90μL balanced salt solution (BSS) plus 0.001% Pluronic F68®. |
|
| Sham-treated Eyes | Sham Comparator | Each participant will have one eye randomly selected to receive GS010 and the other eye will receive a sham injection. Eyes receiving sham injection will undergo the same preparatory procedures as eyes receiving GS010 injection, including pupillary dilation, topical anti-infection and topical anesthetic procedures. Sham Intravitreal injection will be performed by applying pressure to the eye at the location of a typical intravitreal injection procedure using the blunt end of a syringe without a needle. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GS010 | Biological | Both eyes of each participant will receive standard antiseptic preparation, administration of topical local ocular anesthetic agents and will undergo pupillary dilation. Administration of an intra-ocular pressure lowering agent will precede treatment for every participant. GS010-treated Eyes: GS010 is a recombinant adeno-associated viral vector serotype 2 (rAAV2/2) containing the wild-type ND4 gene (rAAV2/2-ND4). Participants will receive a single dose of GS010 in one of their randomly selected eyes, via intravitreal injection containing 9E10 viral genomes in 90μL balanced salt solution (BSS) plus 0.001% Pluronic F68®. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in ETDRS Visual Acuity (Quantitative Score) at Week 48 | Visual acuity was derived from the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The visual acuity logarithm of the minimal angle of resolution (LogMAR) score was derived from the number of letters participants could read on the ETDRS chart. 1 ETDRS line = 5 letters 1 ETDRS line = 0.1 LogMAR A lower LogMAR score denotes better visual acuity and a negative change from baseline indicates an improvement in visual acuity. Change = (Week 48 score - Baseline score). | Baseline and Week 48 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in ETDRS Visual Acuity (Quantitative Score) at Week 96 | Visual acuity was derived from the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The visual acuity logarithm of the minimal angle of resolution (LogMAR) score was derived from the number of letters participants could read on the ETDRS chart. 1 ETDRS line = 5 letters 1 ETDRS line = 0.1 LogMAR A lower LogMAR score denotes better visual acuity and a negative change from baseline indicates an improvement in visual acuity. Change = (Week 96 score - Baseline score). |
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Inclusion Criteria:
Selection Criteria:
Participants must meet all the following criteria at the Screening Visit (Visit 1) in order to be included into the study.
Inclusion Criteria:
Participants included in the study must satisfy all the following criteria at the Inclusion Visit (Visit 2).
Exclusion Criteria:
Non-Selection Criteria:
Participants who meet at least one of the following criteria at the Screening Visit (Visit 1) will not be included into the study.
Exclusion Criteria:
Participants who meet at least one of the following criteria at the Inclusion Visit (Visit 2) will not be included in the study.
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| Name | Affiliation | Role |
|---|---|---|
| Patrick Yu Wai Man, MDPhDFRCOpht | Moorfields Eye Hospital NHS Foundation Trust | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Doheny Eye Center, University of California, Los Angeles | Los Angeles | California | United States | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36449262 | Derived | Carelli V, Newman NJ, Yu-Wai-Man P, Biousse V, Moster ML, Subramanian PS, Vignal-Clermont C, Wang AG, Donahue SP, Leroy BP, Sergott RC, Klopstock T, Sadun AA, Rebolleda Fernandez G, Chwalisz BK, Banik R, Girmens JF, La Morgia C, DeBusk AA, Jurkute N, Priglinger C, Karanjia R, Josse C, Salzmann J, Montestruc F, Roux M, Taiel M, Sahel JA; the LHON Study Group. Indirect Comparison of Lenadogene Nolparvovec Gene Therapy Versus Natural History in Patients with Leber Hereditary Optic Neuropathy Carrying the m.11778G>A MT-ND4 Mutation. Ophthalmol Ther. 2023 Feb;12(1):401-429. doi: 10.1007/s40123-022-00611-x. Epub 2022 Nov 30. | |
| 34108929 |
| Label | URL |
|---|---|
| National Library of Medicine's Genetics Home Reference for Leber Hereditary Optic Neuropathy | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | All Participants | All participants who were enrolled and received both study treatments, GS010 and Sham. All participants in the study received both GS010 and the sham procedure simultaneously. Participants were randomly assigned to receive GS010 in either the right or left eye. The same participants also received the sham procedure in the eye not assigned to GS010, at the same study visit. GS010: Either the right or left eye received one single dose of GS010 (9E10 vg/eye) via an intravitreal (IVT) injection. The volume of the injected formula was 90 µL. The injection was performed in the vitreous humor under local anesthesia. Sham procedure: Either the right or left eye (the eye not randomly assigned to GS010) received the sham procedure. One single sham IVT injection was performed by applying pressure to the eye at the location of a typical IVT injection procedure, using the blunt end of a syringe without a needle. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 7, 2016 | Dec 10, 2019 |
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| Sham Intravitreal Injection | Device | Both eyes of each participant will receive standard antiseptic preparation, administration of topical local ocular anesthetic agents and will undergo pupillary dilation. Administration of an intra-ocular pressure lowering agent will precede treatment for every participant. Sham-treated Eyes: One eye of each participant will undergo sham injection. Sham Intravitreal injection will be performed by applying pressure to the eye at the location of a typical intravitreal injection procedure using the blunt end of a syringe without a needle. |
|
| Baseline and Week 96 |
| Number of Eye Responders to Treatment at Week 48 and Week 96 | An eye was determined as a responder to treatment based on 2 different definitions. Definition 1: An eye responder was defined by an improvement of the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity score of at least 15 letters compared to Baseline, or a final visual acuity greater than a Snellen acuity equivalent of 20/200 (a score of at least 1 letter). Definition 2: An eye responder was defined by an improvement of the ETDRS score of at least 20 letters compared to Baseline. | Baseline; Week 48 and Week 96 |
| Number of Subject Responders to Treatment at Week 48 and Week 96 | A subject responder was defined as a participant whose Early Treatment Diabetic Retinopathy Study (ETDRS) score of the treated eye (that received GS010), was at least 15 letters better than the sham eye, or whose treated eye had a logarithm of the minimal angle of resolution (logMAR) acuity score of at least 0.3 logMAR better than the sham eye. | Week 48 and Week 96 |
| Change From Baseline in GCL Macular Volume at Week 48 and Week 96 | Ganglion cell layer (GCL) macular volume was measured as a parameter of spectral domain-optical coherence tomography (SD-OCT). SD-OCT was obtained with the Spectralis® OCT (Heidelberg Engineering). | Baseline and Week 48; Baseline and Week 96 |
| Change From Baseline in RNFL Temporal Quadrant Thickness at Week 48 and Week 96 | Retinal nerve fiber layer (RNFL) temporal quadrant thickness was measured as a parameter of spectral domain-optical coherence tomography (SD-OCT). SD-OCT was obtained with the Spectralis® OCT (Heidelberg Engineering). | Baseline and Week 48; Baseline and Week 96 |
| Change From Baseline in Papillomacular Bundle Thickness at Week 48 and Week 96 | Papillomacular bundle thickness was measured as a parameter of spectral domain-optical coherence tomography (SD-OCT). SD-OCT was obtained with the Spectralis® OCT (Heidelberg Engineering). | Baseline and Week 48; Baseline and Week 96 |
| Change From Baseline in ETDRS Total Macular Volume at Week 48 and Week 96 | Early Treatment Diabetic Retinopathy Study (ETDRS) total macular volume was measured as a parameter of spectral domain-optical coherence tomography (SD-OCT). SD-OCT was obtained with the Spectralis® OCT (Heidelberg Engineering). | Baseline and Week 48; Baseline and Week 96 |
| Change From Baseline in the Foveal Threshold Sensitivities Obtained With HVF Analyzer II at Week 48 and Week 96 | The assessment of standardized automated visual fields was measured using the Humphrey Visual Field (HVF) Analyzer II. Automated visual fields included the assessment of foveal threshold sensitivities. Foveal threshold sensitivity is measured in decibels (dB), which ranges from 0 dB to 50 dB. A sensitivity threshold of 0 dB indicates not being able to see the most intense perimetric stimulus, while higher dB indicates better/normal foveal vision. A positive change from baseline indicates an improvement of symptoms. | Baseline and Week 48; Baseline and Week 96 |
| Visual Field Mean Deviation in Decibels of Sensitivity Obtained With HVF Analyzer II at Week 48 and Week 96 | The assessment of standardized automated visual fields was measured using the Humphrey Visual Field (HVF) Analyzer II. Automated visual fields included the assessment of the mean deviation (MD) in decibels (dB) of sensitivity. | Baseline, Week 48 and Week 96 |
| Change From Baseline in Contrast Sensitivity at Week 48 and Week 96 | The assessment of contrast sensitivity was measured using the Pelli-Robson chart. The chart uses letters arranged in groups whose contrast varies from high to low. Participants read the letters, starting with the highest contrast, until they are unable to read 2 or 3 letters in a single group. Each eye is assigned a score based on the contrast of the last group in which 2 or 3 letters were correctly read, ranging from 0 to 2.2 "log of contrast sensitivity" (LogCS) units. A score of 2.0 LogCS, represents a normal sensitivity contrast, and indicates the eye was able to detect 2 of the 3 letters with a contrast of 1 percent (contrast sensitivity = 100 percent or log 2). Scores less than 2.0 signify poorer contrast sensitivity. Pelli-Robson contrast sensitivity score of less than 1.5 is consistent with visual impairment and a score of less than 1.0 represents in visual disability. A positive change from baseline indicates improvement in symptoms. | Baseline and Week 48; Baseline and Week 96 |
| Change From Baseline in Color Vision | The assessment of color vision was measured using the Farnsworth-Munsell 100-Hue Color Test. Each of the 4 trays consisted of 21 caps. Participants were asked to sort the randomly arranged caps following the hue order from the first to the last fixed caps. The total error score (TES) was derived by the frequency the caps were misplaced and the severity, or distance of the misplacement. Errors were made whenever caps were misplaced from the correct order. Error scores were calculated according to the distance between any two caps. The error score for each individual cap was the sum of the difference between the number of that cap and the numbers of the cap adjacent to it, minus 2. TES was the total sum of the error scores of the entire set of caps. The best possible score was 0 and there is no defined upper limit to the total error score range. A lower score indicates improved color discrimination ability. A negative change from baseline indicates an improvement in symptoms. | Baseline and Week 48; Baseline and Week 96 |
| Department of Ophthalmology, Emory University School of Medicine |
| Atlanta |
| Georgia |
| 30322 |
| United States |
| Neuro Ophthalmologic Associates, Wills Eye Hospital, Thomas Jefferson University | Philadelphia | Pennsylvania | 19107 | United States |
| Centre National Hospitalier d'Ophtalmologie des Quinze-Vingt | Paris | Paris | France |
| Department of Neurology, University of Munich, Friedrich-Baur-Institute | Munich | 80336 | Germany |
| IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica, Ospedale Bellaria | Bologna | Bologna | Italy |
| Moorfields Eye Hospital NHS Foundation Trust | London | EC1V 2PD | United Kingdom |
| Derived |
| Newman NJ, Yu-Wai-Man P, Carelli V, Biousse V, Moster ML, Vignal-Clermont C, Sergott RC, Klopstock T, Sadun AA, Girmens JF, La Morgia C, DeBusk AA, Jurkute N, Priglinger C, Karanjia R, Josse C, Salzmann J, Montestruc F, Roux M, Taiel M, Sahel JA. Intravitreal Gene Therapy vs. Natural History in Patients With Leber Hereditary Optic Neuropathy Carrying the m.11778G>A ND4 Mutation: Systematic Review and Indirect Comparison. Front Neurol. 2021 May 24;12:662838. doi: 10.3389/fneur.2021.662838. eCollection 2021. |
| National Library of Medicine's Genes and Gene Therapy | View source |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Participants | All participants who were enrolled and received both study treatments, GS010 and Sham. All participants in the study received both GS010 and the sham procedure simultaneously. Participants were randomly assigned to receive GS010 in either the right or left eye. The same participants also received the sham procedure in the eye not assigned to GS010, at the same study visit. GS010: Either the right or left eye received one single dose of GS010 (9E10 vg/eye) via an intravitreal (IVT) injection. The volume of the injected formula was 90 µL. The injection was performed in the vitreous humor under local anesthesia. Sham procedure: Either the right or left eye (the eye not randomly assigned to GS010) received the sham procedure. One single sham IVT injection was performed by applying pressure to the eye at the location of a typical IVT injection procedure, using the blunt end of a syringe without a needle. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
| ||||||||||||||||||
| Weight | Mean | Standard Deviation | kilograms |
| |||||||||||||||||
| Height | Mean | Standard Deviation | centimetres |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in ETDRS Visual Acuity (Quantitative Score) at Week 48 | Visual acuity was derived from the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The visual acuity logarithm of the minimal angle of resolution (LogMAR) score was derived from the number of letters participants could read on the ETDRS chart. 1 ETDRS line = 5 letters 1 ETDRS line = 0.1 LogMAR A lower LogMAR score denotes better visual acuity and a negative change from baseline indicates an improvement in visual acuity. Change = (Week 48 score - Baseline score). | All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit (Week 48). All participants received both GS010 and Sham simultaneously. | Posted | Least Squares Mean | Standard Error | LogMAR | Baseline and Week 48 | Eyes | Eyes |
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| Secondary | Change From Baseline in ETDRS Visual Acuity (Quantitative Score) at Week 96 | Visual acuity was derived from the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The visual acuity logarithm of the minimal angle of resolution (LogMAR) score was derived from the number of letters participants could read on the ETDRS chart. 1 ETDRS line = 5 letters 1 ETDRS line = 0.1 LogMAR A lower LogMAR score denotes better visual acuity and a negative change from baseline indicates an improvement in visual acuity. Change = (Week 96 score - Baseline score). | All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit (Week 96). All participants received both GS010 and Sham simultaneously. | Posted | Least Squares Mean | Standard Error | LogMAR | Baseline and Week 96 |
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| Secondary | Number of Eye Responders to Treatment at Week 48 and Week 96 | An eye was determined as a responder to treatment based on 2 different definitions. Definition 1: An eye responder was defined by an improvement of the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity score of at least 15 letters compared to Baseline, or a final visual acuity greater than a Snellen acuity equivalent of 20/200 (a score of at least 1 letter). Definition 2: An eye responder was defined by an improvement of the ETDRS score of at least 20 letters compared to Baseline. | All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit (Week 48 or Week 96). All participants received both GS010 and Sham simultaneously. | Posted | Count of Units | Eyes | Baseline; Week 48 and Week 96 | Eyes | Eyes |
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| Secondary | Number of Subject Responders to Treatment at Week 48 and Week 96 | A subject responder was defined as a participant whose Early Treatment Diabetic Retinopathy Study (ETDRS) score of the treated eye (that received GS010), was at least 15 letters better than the sham eye, or whose treated eye had a logarithm of the minimal angle of resolution (logMAR) acuity score of at least 0.3 logMAR better than the sham eye. | All participants that received study treatments, with data at the applicable post dose visit (Week 48 or Week 96). All participants received both GS010 and Sham simultaneously. | Posted | Count of Participants | Participants | Week 48 and Week 96 |
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| Secondary | Change From Baseline in GCL Macular Volume at Week 48 and Week 96 | Ganglion cell layer (GCL) macular volume was measured as a parameter of spectral domain-optical coherence tomography (SD-OCT). SD-OCT was obtained with the Spectralis® OCT (Heidelberg Engineering). | All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit (Week 48 or Week 96). All participants received both GS010 and Sham simultaneously. | Posted | Least Squares Mean | Standard Error | mm^3 | Baseline and Week 48; Baseline and Week 96 | Eyes | Eyes |
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| Secondary | Change From Baseline in RNFL Temporal Quadrant Thickness at Week 48 and Week 96 | Retinal nerve fiber layer (RNFL) temporal quadrant thickness was measured as a parameter of spectral domain-optical coherence tomography (SD-OCT). SD-OCT was obtained with the Spectralis® OCT (Heidelberg Engineering). | All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit (Week 48 or Week 96). All participants received both GS010 and Sham simultaneously. | Posted | Least Squares Mean | Standard Error | µm | Baseline and Week 48; Baseline and Week 96 | Eyes | Eyes |
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| Secondary | Change From Baseline in Papillomacular Bundle Thickness at Week 48 and Week 96 | Papillomacular bundle thickness was measured as a parameter of spectral domain-optical coherence tomography (SD-OCT). SD-OCT was obtained with the Spectralis® OCT (Heidelberg Engineering). | All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit (Week 48 or Week 96). All participants received both GS010 and Sham simultaneously. | Posted | Least Squares Mean | Standard Error | µm | Baseline and Week 48; Baseline and Week 96 | Eyes | Eyes |
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| Secondary | Change From Baseline in ETDRS Total Macular Volume at Week 48 and Week 96 | Early Treatment Diabetic Retinopathy Study (ETDRS) total macular volume was measured as a parameter of spectral domain-optical coherence tomography (SD-OCT). SD-OCT was obtained with the Spectralis® OCT (Heidelberg Engineering). | All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit (Week 48 or Week 96). All participants received both GS010 and Sham simultaneously. | Posted | Least Squares Mean | Standard Error | mm^3 | Baseline and Week 48; Baseline and Week 96 | Eyes | Eyes |
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| Secondary | Change From Baseline in the Foveal Threshold Sensitivities Obtained With HVF Analyzer II at Week 48 and Week 96 | The assessment of standardized automated visual fields was measured using the Humphrey Visual Field (HVF) Analyzer II. Automated visual fields included the assessment of foveal threshold sensitivities. Foveal threshold sensitivity is measured in decibels (dB), which ranges from 0 dB to 50 dB. A sensitivity threshold of 0 dB indicates not being able to see the most intense perimetric stimulus, while higher dB indicates better/normal foveal vision. A positive change from baseline indicates an improvement of symptoms. | All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit (Week 48 or Week 96). All participants received both GS010 and Sham simultaneously. | Posted | Mean | Standard Deviation | decibels (dB) | Baseline and Week 48; Baseline and Week 96 | Eyes | Eyes |
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| Secondary | Visual Field Mean Deviation in Decibels of Sensitivity Obtained With HVF Analyzer II at Week 48 and Week 96 | The assessment of standardized automated visual fields was measured using the Humphrey Visual Field (HVF) Analyzer II. Automated visual fields included the assessment of the mean deviation (MD) in decibels (dB) of sensitivity. | All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit (Week 48 or Week 96). All participants received both GS010 and Sham simultaneously. | Posted | Mean | Standard Deviation | decibels (dB) | Baseline, Week 48 and Week 96 | Eyes | Eyes |
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| Secondary | Change From Baseline in Contrast Sensitivity at Week 48 and Week 96 | The assessment of contrast sensitivity was measured using the Pelli-Robson chart. The chart uses letters arranged in groups whose contrast varies from high to low. Participants read the letters, starting with the highest contrast, until they are unable to read 2 or 3 letters in a single group. Each eye is assigned a score based on the contrast of the last group in which 2 or 3 letters were correctly read, ranging from 0 to 2.2 "log of contrast sensitivity" (LogCS) units. A score of 2.0 LogCS, represents a normal sensitivity contrast, and indicates the eye was able to detect 2 of the 3 letters with a contrast of 1 percent (contrast sensitivity = 100 percent or log 2). Scores less than 2.0 signify poorer contrast sensitivity. Pelli-Robson contrast sensitivity score of less than 1.5 is consistent with visual impairment and a score of less than 1.0 represents in visual disability. A positive change from baseline indicates improvement in symptoms. | All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit (Week 48 or Week 96). All participants received both GS010 and Sham simultaneously. | Posted | Least Squares Mean | Standard Error | LogCS | Baseline and Week 48; Baseline and Week 96 | Eyes | Eyes |
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| Secondary | Change From Baseline in Color Vision | The assessment of color vision was measured using the Farnsworth-Munsell 100-Hue Color Test. Each of the 4 trays consisted of 21 caps. Participants were asked to sort the randomly arranged caps following the hue order from the first to the last fixed caps. The total error score (TES) was derived by the frequency the caps were misplaced and the severity, or distance of the misplacement. Errors were made whenever caps were misplaced from the correct order. Error scores were calculated according to the distance between any two caps. The error score for each individual cap was the sum of the difference between the number of that cap and the numbers of the cap adjacent to it, minus 2. TES was the total sum of the error scores of the entire set of caps. The best possible score was 0 and there is no defined upper limit to the total error score range. A lower score indicates improved color discrimination ability. A negative change from baseline indicates an improvement in symptoms. | All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit (Week 48 or Week 96). All participants received both GS010 and Sham simultaneously. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Week 48; Baseline and Week 96 | Eyes | Eyes |
|
From first dose to end of study (a maximum of 96 weeks)
Because participants received both treatment and sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular AEs. Reported events include AEs associated with sham procedure.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | All Participants | All participants who were enrolled and received both study treatments, GS010 and Sham. Participants were randomly assigned to receive GS010 in either the right or left eye. The same participants also received the sham comparator in the eye not assigned to GS010 at the same visit. GS010: Either the right or left eye received one single dose of GS010 (9E10 vg/eye) via an intravitreal (IVT) injection. The volume of the injected formula was 90 µL. The injection was performed in the vitreous humor under local anesthesia. Sham procedure: Either the right or left eye (the eye not randomly assigned to GS010) received the sham procedure. One single sham IVT injection was performed by applying pressure to the eye at the location of a typical IVT injection procedure, using the blunt end of a syringe without a needle. | 0 | 37 | 3 | 37 | 37 | 37 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute myocardial infarction | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Retinal tear | Eye disorders | MedDRA 20.1 | Systematic Assessment | This event occurred only in an eye receiving the sham procedure. |
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| Intestinal perforation | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Diverticulitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypertension | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
| |
| Gamma-glutamyl transferase increased | Investigations | MedDRA 20.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 20.1 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 20.1 | Systematic Assessment |
| |
| Drug hypersensitivity | Immune system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Alcohol use | Social circumstances | MedDRA 20.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Anterior chamber cell | Eye disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Autoimmune uveitis | Eye disorders | MedDRA 20.1 | Systematic Assessment | The verbatim AE term is "intermediate uveitis". 1/14 affected participants experienced this event only in sham-treated eyes. |
|
| Cataract | Eye disorders | MedDRA 20.1 | Systematic Assessment | 1/4 affected participants experienced this event only in sham-treated eyes |
|
| Conjunctival haemorrhage | Eye disorders | MedDRA 20.1 | Systematic Assessment | 3/6 affected participants experienced this event only in sham-treated eyes. |
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| Conjunctival hyperaemia | Eye disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA 20.1 | Systematic Assessment | 1/2 affected participants experienced this event only in sham-treated eyes. |
|
| Iridocyclitis | Eye disorders | MedDRA 20.1 | Systematic Assessment | 1/15 affected participants experienced this event only in sham-treated eyes. |
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| Iritis | Eye disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Keratic precipitates | Eye disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Eye pain | Eye disorders | MedDRA 20.1 | Systematic Assessment | 1/3 affected participants experienced this event only in sham-treated eyes. |
|
| Intraocular pressure increased | Eye disorders | MedDRA 20.1 | Systematic Assessment | 1/11 affected participants experienced this event only in sham-treated eyes. |
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| Vitritis | Eye disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Vitreous floaters | Eye disorders | MedDRA 20.1 | Systematic Assessment |
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| Vitreous detachment | Eye disorders | MedDRA 20.1 | Systematic Assessment |
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| Vitreal cells | Eye disorders | MedDRA 20.1 | Systematic Assessment | 1/7 affected participants experienced this event only in sham-treated eyes. |
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| Visual impairment | Eye disorders | MedDRA 20.1 | Systematic Assessment |
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| Punctate keratitis | Eye disorders | MedDRA 20.1 | Systematic Assessment | 4/15 affected participants experienced this event only in sham-treated eyes. |
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| Depression | Psychiatric disorders | MedDRA 20.1 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Regulatory Affairs | GenSight Biologics | 176217220 | 0033 | ipengue@gensight-biologics.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 12, 2018 | Dec 10, 2019 | SAP_001.pdf |
| ID | Term |
|---|---|
| D029242 | Optic Atrophy, Hereditary, Leber |
| D005128 | Eye Diseases |
| D015785 | Eye Diseases, Hereditary |
| D030342 | Genetic Diseases, Inborn |
| D028361 | Mitochondrial Diseases |
| D009422 | Nervous System Diseases |
| D019636 | Neurodegenerative Diseases |
| ID | Term |
|---|---|
| D015418 | Optic Atrophies, Hereditary |
| D009896 | Optic Atrophy |
| D009901 | Optic Nerve Diseases |
| D003389 | Cranial Nerve Diseases |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
| >=65 years |
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| France |
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| Germany |
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| Italy |
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| Units | Counts |
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| Participants |
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All eyes that received the Sham. Each participant was randomly assigned GS010 in either the right or left eye, the eye not assigned GS010 received the sham procedure. The eye assigned to the Sham received one single sham intravitreal (IVT) injection, which was performed by applying pressure to the eye at the location of a typical IVT injection procedure, using the blunt end of a syringe without a needle. The same participants also received GS010 in the right or left eye, which did not receive the sham procedure, at the same study visit. |
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| OG001 | Sham-treated Eyes | All eyes that received the Sham. Each participant was randomly assigned GS010 in either the right or left eye, the eye not assigned GS010 received the sham procedure. The eye assigned to the Sham received one single sham intravitreal (IVT) injection, which was performed by applying pressure to the eye at the location of a typical IVT injection procedure, using the blunt end of a syringe without a needle. The same participants also received GS010 in the right or left eye, which did not receive the sham procedure, at the same study visit. |
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| OG001 | Sham-treated Eyes | All eyes that received the Sham. Each participant was randomly assigned GS010 in either the right or left eye, the eye not assigned GS010 received the sham procedure. The eye assigned to the Sham received one single sham intravitreal (IVT) injection, which was performed by applying pressure to the eye at the location of a typical IVT injection procedure, using the blunt end of a syringe without a needle. The same participants also received GS010 in the right or left eye, which did not receive the sham procedure, at the same study visit. |
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