Optic, Atrophy, Hereditary, Leber
Conditions
Keywords
Leber Hereditary Optic Neuropathy, Leber Hereditary Optic Atrophy, Heredity Optic Atrophy, Eye Diseases, Hereditary Eye Diseases, Inborn Genetic Disease, Genetic Therapy, Intravitreal Injections, Mitochondrial Disease, AAV2 Vectors, Nervous System Diseases, Neurodegenerative Disease, Heredodegenerative Disorders of the Nervous System
Brief summary
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.
Interventions
BIOLOGICALGS010
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®.
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.
Sponsors
GenSight Biologics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
No
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. 1. Age 15 years or older. 2. Onset of vision loss based on medically documented history or participant testimony, in at least one eye for ≤180 days in duration and if both eyes are affected the duration of vision loss in both eyes must be ≤180 days in duration. 3. Each eye of the participant maintaining visual ability to allow at least for counting of the examiner's fingers at any distance. 4. Female participants (if of childbearing potential) must agree to use effective methods of birth control up to 6 months after intravitreal (IVT) injection and male participants must agree to use condoms for up to 6 months after IVT injection. 5. Ability to obtain adequate pupillary dilation to permit thorough ocular examination and testing. 6. Signed written informed consent. 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. 3. Have a negative test for infection with human immunodeficiency virus. 4. Have a negative pregnancy test for women of childbearing potential (a woman who is 2 years post-menopausal or surgically sterile is not considered to be of childbearing potential).
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. 1. Any known allergy or hypersensitivity to GS010 or its constituents. 2. Contraindication to IVT injection. 3. IVT drug delivery to either eye within 30 days prior to the Screening Visit (Visit 1). 4. Previous vitrectomy in either eye. 5. Narrow angle in either eye contra-indicating pupillary dilation. 6. Presence of disorders of the ocular media, such as the cornea and lens, which may interfere with visual acuity and other ocular assessments during the study period. 7. Vision disorders, other than LHON, involving visual disability or with the potential to cause further vision loss during the trial period. 8. Causes of optic neuropathy other than LHON and glaucoma. 9. Participants with known mutations of other genes involved in pathological retinal or optic nerve conditions. 10. Presence of ocular or systemic disease, other than LHON, whose pathology or associated treatments might affect the retina or the optic nerve. 11. History of amblyopia associated with a Snellen visual acuity equivalent of worse than 20/80 (equivalent to 6/24 at 6 meters, decimal acuity 0.25, LogMAR +0.6) in the affected eye. 12. Presence of ocular conditions, which in the opinion of the Investigator will prevent good quality SD-OCT imaging from being obtained. 13. Presence, in either eye, of uncontrolled glaucoma, defined as an intra-ocular pressure (IOP) greater than 25 mmHg, despite maximal medical therapy with IOP-lowering agents. 14. Active ocular inflammation or history of idiopathic or autoimmune-associated uveitis. 15. Participants participating in another clinical trial and receiving an investigational medicinal product within 90 days prior to the Screening Visit (Visit 1). 16. Previous treatment with an ocular gene therapy product. 17. Participants who have undergone ocular surgery of clinical relevance (per Investigator opinion) within 90 days preceding the Screening Visit (Visit 1). 18. Female participants who are or who intend to breast feed during the trial period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in ETDRS Visual Acuity (Quantitative Score) at Week 48 | Baseline and Week 48 | Visual acuity was derived from the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Visual acuity is measured in "logarithm of the minimal angle of resolution" (LogMAR), which 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. A positive change from baseline indicates a worsening in symptoms. Change = (Week 48 score - Baseline score). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in ETDRS Visual Acuity (Quantitative Score) | Baseline; Week 72 and Week 96 | Visual acuity was derived from the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Visual acuity is measured in "logarithm of the minimal angle of resolution" (LogMAR), which 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. A positive change from baseline indicates a worsening in symptoms. Change = (Week 72 score - Baseline score) or (Week 96 score - Baseline score). Missing data was imputed by the linear interpolation method. |
| Number of Eye Responders to Treatment | Baseline; Week 48; Week 72 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. |
| Number of Subject Responders to Treatment | Week 48; Week 72 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. For the Week 96 analysis, if no score was available for Week 96, the score from the previous visit was used. |
| Change From Baseline in GCL Macular Volume | Baseline; Week 48; Week 72 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). |
| Change From Baseline in RNFL Temporal Quadrant Thickness | Baseline; Week 48; Week 72 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). |
| Change From Baseline in RNFL Papillomacular Bundle Thickness | Baseline; Week 48; Week 72 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). |
| Change From Baseline in ETDRS Total Macular Volume | Baseline; Week 48; Week 72 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). |
| Change From Baseline in the Foveal Threshold Sensitivities Obtained With HVF Analyzer II | Baseline; Week 48; Week 72 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. |
| Visual Field Mean Deviation in Decibels of Sensitivity Obtained With HVF Analyzer II | Baseline; Week 48; Week 72 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. |
| Change From Baseline in Contrast Sensitivity | Baseline; Week 48; Week 72 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 negative change from baseline indicates worsening in symptoms. |
| Change From Baseline in Color Vision | Baseline; Week 48 and Week 96 | 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 positive change from baseline indicates a worsening in symptoms. |
Countries
France, Germany, Italy, United Kingdom, United States
Contacts
PRINCIPAL_INVESTIGATORNancy J. Newman, MD
Department of Ophthalmology, Emory University School of Medicine
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 receive 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: 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. | 39 |
| Total | 39 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 36.3 years STANDARD_DEVIATION 15.5 |
| Height | 174.5 centimeters STANDARD_DEVIATION 7.7 |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 32 Participants |
| Weight | 73.9 kilograms STANDARD_DEVIATION 17.8 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 39 |
| other Total, other adverse events | 38 / 39 |
| serious Total, serious adverse events | 3 / 39 |
Outcome results
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. Visual acuity is measured in logarithm of the minimal angle of resolution (LogMAR), which 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. A positive change from baseline indicates a worsening in symptoms. Change = (Week 48 score - Baseline score).
Time frame: Baseline and Week 48
Population: Intent-to-treat (ITT) population: All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit. 1 participant was excluded from the ITT population due to receiving a smaller volume of study treatment than specified in the protocol. Participants received GS010 and Sham simultaneously.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| GS010-treated Eyes | Change From Baseline in ETDRS Visual Acuity (Quantitative Score) at Week 48 | 0.380 LogMAR | Standard Error 0.129 |
| Sham-treated Eyes | Change From Baseline in ETDRS Visual Acuity (Quantitative Score) at Week 48 | 0.392 LogMAR | Standard Error 0.129 |
Comparison: A mixed model of analysis of covariance (ANCOVA) was used with change from baseline at Week 48 as the response, and participants, eyes of the participant as random factor, treatment and baseline LogMAR value as covariates in the model. P-value is used to assess the significance of the difference between All-GS010 and All-Sham with respect to change of LogMAR from baseline.p-value: 0.88995% CI: [-0.182, 0.158]ANCOVA
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 positive change from baseline indicates a worsening in symptoms.
Time frame: Baseline; Week 48 and Week 96
Population: Intent-to-treat (ITT) population: All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit. 1 participant was excluded from the ITT population due to receiving a smaller volume of study treatment than specified in the protocol. Participants received GS010 and Sham simultaneously.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GS010-treated Eyes | Change From Baseline in Color Vision | Week 48 | 133.1 score on a scale | Standard Deviation 290.7 |
| GS010-treated Eyes | Change From Baseline in Color Vision | Week 96 | 97.7 score on a scale | Standard Deviation 342.2 |
| Sham-treated Eyes | Change From Baseline in Color Vision | Week 48 | 235.6 score on a scale | Standard Deviation 392.3 |
| Sham-treated Eyes | Change From Baseline in Color Vision | Week 96 | 213.5 score on a scale | Standard Deviation 393.1 |
Secondary
Change From Baseline in Contrast Sensitivity
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 negative change from baseline indicates worsening in symptoms.
Time frame: Baseline; Week 48; Week 72 and Week 96
Population: Intent-to-treat (ITT) population: All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit. 1 participant was excluded from the ITT population due to receiving a smaller volume of study treatment than specified in the protocol. Participants received GS010 and Sham simultaneously.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| GS010-treated Eyes | Change From Baseline in Contrast Sensitivity | Week 48 | -0.35 LogCS | Standard Error 0.07 |
| GS010-treated Eyes | Change From Baseline in Contrast Sensitivity | Week 72 | -0.25 LogCS | Standard Error 0.07 |
| GS010-treated Eyes | Change From Baseline in Contrast Sensitivity | Week 96 | -0.27 LogCS | Standard Error 0.07 |
| Sham-treated Eyes | Change From Baseline in Contrast Sensitivity | Week 48 | -0.33 LogCS | Standard Error 0.07 |
| Sham-treated Eyes | Change From Baseline in Contrast Sensitivity | Week 72 | -0.28 LogCS | Standard Error 0.07 |
| Sham-treated Eyes | Change From Baseline in Contrast Sensitivity | Week 96 | -0.25 LogCS | Standard Error 0.07 |
Secondary
Change From Baseline in ETDRS Total Macular Volume
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).
Time frame: Baseline; Week 48; Week 72 and Week 96
Population: Intent-to-treat (ITT) population: All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit. 1 participant was excluded from the ITT population due to receiving a smaller volume of study treatment than specified in the protocol. Participants received GS010 and Sham simultaneously.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| GS010-treated Eyes | Change From Baseline in ETDRS Total Macular Volume | Week 48 | -0.578 mm^3 | Standard Error 0.041 |
| GS010-treated Eyes | Change From Baseline in ETDRS Total Macular Volume | Week 72 | -0.686 mm^3 | Standard Error 0.048 |
| GS010-treated Eyes | Change From Baseline in ETDRS Total Macular Volume | Week 96 | -0.720 mm^3 | Standard Error 0.05 |
| Sham-treated Eyes | Change From Baseline in ETDRS Total Macular Volume | Week 48 | -0.708 mm^3 | Standard Error 0.04 |
| Sham-treated Eyes | Change From Baseline in ETDRS Total Macular Volume | Week 72 | -0.782 mm^3 | Standard Error 0.048 |
| Sham-treated Eyes | Change From Baseline in ETDRS Total Macular Volume | Week 96 | -0.800 mm^3 | Standard Error 0.05 |
Secondary
Change From Baseline in ETDRS Visual Acuity (Quantitative Score)
Visual acuity was derived from the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Visual acuity is measured in logarithm of the minimal angle of resolution (LogMAR), which 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. A positive change from baseline indicates a worsening in symptoms. Change = (Week 72 score - Baseline score) or (Week 96 score - Baseline score). Missing data was imputed by the linear interpolation method.
Time frame: Baseline; Week 72 and Week 96
Population: Intent-to-treat (ITT) population: All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit. 1 participant was excluded from the ITT population due to receiving a smaller volume of study treatment than specified in the protocol. Participants received GS010 and Sham simultaneously.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| GS010-treated Eyes | Change From Baseline in ETDRS Visual Acuity (Quantitative Score) | Week 72 | 0.192 LogMAR | Standard Error 0.104 |
| GS010-treated Eyes | Change From Baseline in ETDRS Visual Acuity (Quantitative Score) | Week 96 | 0.178 LogMAR | Standard Error 0.12 |
| Sham-treated Eyes | Change From Baseline in ETDRS Visual Acuity (Quantitative Score) | Week 72 | 0.216 LogMAR | Standard Error 0.104 |
| Sham-treated Eyes | Change From Baseline in ETDRS Visual Acuity (Quantitative Score) | Week 96 | 0.207 LogMAR | Standard Error 0.12 |
Secondary
Change From Baseline in GCL Macular Volume
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).
Time frame: Baseline; Week 48; Week 72 and Week 96
Population: Intent -to-treat (ITT) population: All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit. 1 participant was excluded from the ITT population due to receiving a smaller volume of study treatment than specified in the protocol. Participants received GS010 and Sham simultaneously.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| GS010-treated Eyes | Change From Baseline in GCL Macular Volume | Week 48 | -0.184 mm^3 | Standard Error 0.014 |
| GS010-treated Eyes | Change From Baseline in GCL Macular Volume | Week 72 | -0.204 mm^3 | Standard Error 0.015 |
| GS010-treated Eyes | Change From Baseline in GCL Macular Volume | Week 96 | -0.208 mm^3 | Standard Error 0.015 |
| Sham-treated Eyes | Change From Baseline in GCL Macular Volume | Week 48 | -0.207 mm^3 | Standard Error 0.014 |
| Sham-treated Eyes | Change From Baseline in GCL Macular Volume | Week 72 | -0.226 mm^3 | Standard Error 0.015 |
| Sham-treated Eyes | Change From Baseline in GCL Macular Volume | Week 96 | -0.221 mm^3 | Standard Error 0.015 |
Secondary
Change From Baseline in RNFL Papillomacular Bundle Thickness
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).
Time frame: Baseline; Week 48; Week 72 and Week 96
Population: Intent-to-treat (ITT) population: All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit. 1 participant was excluded from the ITT population due to receiving a smaller volume of study treatment than specified in the protocol. Participants received GS010 and Sham simultaneously.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| GS010-treated Eyes | Change From Baseline in RNFL Papillomacular Bundle Thickness | Week 48 | -10.4 µm | Standard Error 1 |
| GS010-treated Eyes | Change From Baseline in RNFL Papillomacular Bundle Thickness | Week 72 | -12.8 µm | Standard Error 1 |
| GS010-treated Eyes | Change From Baseline in RNFL Papillomacular Bundle Thickness | Week 96 | -11.2 µm | Standard Error 1 |
| Sham-treated Eyes | Change From Baseline in RNFL Papillomacular Bundle Thickness | Week 48 | -12.4 µm | Standard Error 1 |
| Sham-treated Eyes | Change From Baseline in RNFL Papillomacular Bundle Thickness | Week 72 | -13.1 µm | Standard Error 1 |
| Sham-treated Eyes | Change From Baseline in RNFL Papillomacular Bundle Thickness | Week 96 | -13.3 µm | Standard Error 1 |
Secondary
Change From Baseline in RNFL Temporal Quadrant Thickness
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).
Time frame: Baseline; Week 48; Week 72 and Week 96
Population: Intent-to-treat (ITT) population: All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit. 1 participant was excluded from the ITT population due to receiving a smaller volume of study treatment than specified in the protocol. Participants received GS010 and Sham simultaneously.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| GS010-treated Eyes | Change From Baseline in RNFL Temporal Quadrant Thickness | Week 48 | -22.8 µm | Standard Error 1 |
| GS010-treated Eyes | Change From Baseline in RNFL Temporal Quadrant Thickness | Week 72 | -25.5 µm | Standard Error 0.9 |
| GS010-treated Eyes | Change From Baseline in RNFL Temporal Quadrant Thickness | Week 96 | -24.2 µm | Standard Error 0.8 |
| Sham-treated Eyes | Change From Baseline in RNFL Temporal Quadrant Thickness | Week 48 | -24.7 µm | Standard Error 1 |
| Sham-treated Eyes | Change From Baseline in RNFL Temporal Quadrant Thickness | Week 72 | -26.0 µm | Standard Error 0.9 |
| Sham-treated Eyes | Change From Baseline in RNFL Temporal Quadrant Thickness | Week 96 | -26.1 µm | Standard Error 0.8 |
Secondary
Change From Baseline in the Foveal Threshold Sensitivities Obtained With HVF Analyzer II
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.
Time frame: Baseline; Week 48; Week 72 and Week 96
Population: Intent-to-treat (ITT) population: All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit. 1 participant was excluded from the ITT population due to receiving a smaller volume of study treatment than specified in the protocol. Participants received GS010 and Sham simultaneously.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GS010-treated Eyes | Change From Baseline in the Foveal Threshold Sensitivities Obtained With HVF Analyzer II | Week 48 | 3.5 decibels (dB) | Standard Deviation 12.3 |
| GS010-treated Eyes | Change From Baseline in the Foveal Threshold Sensitivities Obtained With HVF Analyzer II | Week 72 | 6.3 decibels (dB) | Standard Deviation 7.8 |
| GS010-treated Eyes | Change From Baseline in the Foveal Threshold Sensitivities Obtained With HVF Analyzer II | Week 96 | 3.3 decibels (dB) | Standard Deviation 12.7 |
| Sham-treated Eyes | Change From Baseline in the Foveal Threshold Sensitivities Obtained With HVF Analyzer II | Week 48 | -7.4 decibels (dB) | Standard Deviation 12.8 |
| Sham-treated Eyes | Change From Baseline in the Foveal Threshold Sensitivities Obtained With HVF Analyzer II | Week 72 | -5.1 decibels (dB) | Standard Deviation 11.9 |
| Sham-treated Eyes | Change From Baseline in the Foveal Threshold Sensitivities Obtained With HVF Analyzer II | Week 96 | 1.4 decibels (dB) | Standard Deviation 19.5 |
Secondary
Number of Eye Responders to Treatment
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.
Time frame: Baseline; Week 48; Week 72 and Week 96
Population: Intent-to-treat (ITT) population: All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit. 1 participant was excluded from the ITT population due to receiving a smaller volume of study treatment than specified in the protocol. Participants received GS010 and Sham simultaneously.
| Arm | Measure | Group | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| GS010-treated Eyes | Number of Eye Responders to Treatment | Week 48 Definition 1 | 4 Eyes |
| GS010-treated Eyes | Number of Eye Responders to Treatment | Week 48 Definition 2 | 9 Eyes |
| GS010-treated Eyes | Number of Eye Responders to Treatment | Week 72 Definition 1 | 6 Eyes |
| GS010-treated Eyes | Number of Eye Responders to Treatment | Week 72 Definition 2 | 11 Eyes |
| GS010-treated Eyes | Number of Eye Responders to Treatment | Week 96 Definition 1 | 7 Eyes |
| GS010-treated Eyes | Number of Eye Responders to Treatment | Week 96 Definition 2 | 13 Eyes |
| Sham-treated Eyes | Number of Eye Responders to Treatment | Week 96 Definition 1 | 5 Eyes |
| Sham-treated Eyes | Number of Eye Responders to Treatment | Week 48 Definition 1 | 3 Eyes |
| Sham-treated Eyes | Number of Eye Responders to Treatment | Week 72 Definition 2 | 9 Eyes |
| Sham-treated Eyes | Number of Eye Responders to Treatment | Week 48 Definition 2 | 10 Eyes |
| Sham-treated Eyes | Number of Eye Responders to Treatment | Week 96 Definition 2 | 11 Eyes |
| Sham-treated Eyes | Number of Eye Responders to Treatment | Week 72 Definition 1 | 5 Eyes |
Secondary
Number of Subject Responders to Treatment
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. For the Week 96 analysis, if no score was available for Week 96, the score from the previous visit was used.
Time frame: Week 48; Week 72 and Week 96
Population: Intent-to-treat (ITT) population: All participants that received study treatments, with data at the applicable post-dose visit. 1 participant was excluded from the ITT population due to receiving a smaller volume of study treatment than specified in the protocol. Participants received GS010 and Sham simultaneously.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GS010-treated Eyes | Number of Subject Responders to Treatment | Week 48 | 4 Participants |
| GS010-treated Eyes | Number of Subject Responders to Treatment | Week 72 | 2 Participants |
| GS010-treated Eyes | Number of Subject Responders to Treatment | Week 96 | 5 Participants |
Secondary
Visual Field Mean Deviation in Decibels of Sensitivity Obtained With HVF Analyzer II
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.
Time frame: Baseline; Week 48; Week 72 and Week 96
Population: Intent-to-treat (ITT) population: All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit. 1 participant was excluded from the ITT population due to receiving a smaller volume of study treatment than specified in the protocol. Participants received GS010 and Sham simultaneously.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GS010-treated Eyes | Visual Field Mean Deviation in Decibels of Sensitivity Obtained With HVF Analyzer II | Week 48 MD | -24.26 decibels (dB) | Standard Deviation 9.37 |
| GS010-treated Eyes | Visual Field Mean Deviation in Decibels of Sensitivity Obtained With HVF Analyzer II | Week 96 MD | -23.31 decibels (dB) | Standard Deviation 9.41 |
| GS010-treated Eyes | Visual Field Mean Deviation in Decibels of Sensitivity Obtained With HVF Analyzer II | Week 72 MD | -23.33 decibels (dB) | Standard Deviation 9.41 |
| GS010-treated Eyes | Visual Field Mean Deviation in Decibels of Sensitivity Obtained With HVF Analyzer II | Baseline MD | -16.26 decibels (dB) | Standard Deviation 10.59 |
| Sham-treated Eyes | Visual Field Mean Deviation in Decibels of Sensitivity Obtained With HVF Analyzer II | Week 72 MD | -22.94 decibels (dB) | Standard Deviation 10.11 |
| Sham-treated Eyes | Visual Field Mean Deviation in Decibels of Sensitivity Obtained With HVF Analyzer II | Week 48 MD | -23.76 decibels (dB) | Standard Deviation 10.4 |
| Sham-treated Eyes | Visual Field Mean Deviation in Decibels of Sensitivity Obtained With HVF Analyzer II | Baseline MD | -16.73 decibels (dB) | Standard Deviation 11.48 |
| Sham-treated Eyes | Visual Field Mean Deviation in Decibels of Sensitivity Obtained With HVF Analyzer II | Week 96 MD | -22.70 decibels (dB) | Standard Deviation 9.88 |