Dry Age-related Macular Degeneration
Conditions
Keywords
Dry age-related macular degeneration, Geographic atrophy, Retinal disease, Eye disease, Retinal degeneration, Macular atrophy
Brief summary
The purpose of this clinical study was to evaluate the safety and efficacy of two doses of GT005 administered as a single subretinal injection in subjects with geographic atrophy secondary to age-related macular degeneration (AMD).
Detailed description
This was a Phase II, open-label, outcomes-assessor masked, multicenter, randomized, controlled study designed to evaluate the safety and efficacy of two doses of GT005 administered as a single-time subretinal injection in subjects with Geographic atrophy (GA) secondary to Age-related macular degeneration (AMD). Approximately 250 subjects, across Stage 1 and Stage 2, were planned to be randomized to one of two doses of GT005 or the untreated control group. Subjects entered the study had genotyping and serum Complement factor I (CFI) levels assessed either through participation in a previous Gyroscope sponsored study, or a Sponsor-approved laboratory during the HORIZON screening period. If both eyes are eligible; the eye with the worse visual acuity will be selected as the study eye. If subjects failed to meet the eligibility criteria for this study, they were classified as screen failures and could be considered for entry into another Novartis/Gyroscope sponsored study. After providing the informed consent, subjects underwent ophthalmic and clinical assessments to determined eligibility for inclusion in the study. Upon confirmation of eligibility, subjects were randomized to one of two dose groups (medium dose \[5E10 vg\] or high dose \[2E11 vg\]). Within each dose group, subjects were allocated to GT005, or untreated control based on a 2:1 ratio. The overall study population (N=approximately 250) aimed to include approximately 60% of subjects with foveal GA and 40% of subjects with non-foveal GA (extrafoveal lesions). The study eye was identified for all subjects. Enrolment for HORIZON were composed of two stages. Stage 1 enrolled subjects with foveal or non-foveal GA until 180 subjects were randomized. Stage 2 enrolled subjects with nonfoveal GA. Subjects with a CFI rare variant associated with normal or low serum CFI were also allowed to be enrolled in Stage 2, irrespective of GA foveal involvement. Subjects were stratified by GA lesion size on Fundus autofluorescence (FAF) (≤10 mm2 or \>10 mm2) and AMD genotype subgroup. Randomization of study eyes in the GA lesion size upper stratum of \>10 mm2 to 17.5 mm2 was capped at 20% of total subjects randomized in Stage 1 and Stage 2, respectively. In Stage 2, once enrolment capping at 20% based on upper GA lesion size was reached, eyes that fulfilled the cap criteria were no longer eligible, unless the subject had a CFI rare variant genotype (minor allele frequency ≤1%) previously associated with normal or low serum CFI or had an unreported CFI rare variant genotype (Group 1 and 5). A permuted-block method was used to obtain an approximately 2:1 ratio between GT005 and the untreated control groups for each dose group within each stratum. Following randomization, the Investigator was informed of the subject's allocated treatment (GT005 or the untreated control group) and the study eye selected. To minimize bias during imaging grading, all imaging endpoint assessments and grading were performed at a Central reading centre (CRC). All imaging efficacy assessments were performed in a masked fashion. The Sponsor, subjects, investigators, and study personnel performing clinical assessments remained masked to the dose received for those allocated to GT005. For each subject, the study comprised of a screening period lasting up to 8 weeks (or up to 12 weeks if agreed by the Sponsor Medical Monitor) followed by a 96-week study period. All subjects were assessed for the occurrence of AEs at each visit and underwent functional assessments, retinal imaging, and biological sampling as per the schedule of assessments. This study was conducted in compliance with Independent ethics committees (IECs) / Institutional review boards (IRBs), informed consent regulations, the Declaration of Helsinki, International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) Guidelines, and the Food and Drug Administration (FDA), 21 Code of Federal Regulations (CFR) Part 11, Electronic Records, Electronic Signatures, and FDA, Guidance for Industry: Computerised Systems Used in Clinical Trials. On 24-Aug-2023, the decision was taken to terminate the study and the GT005 program. The decision was aligned with the recommendation of an independent Data monitoring committee (DMC), which concluded that futility criteria had been met for the HORIZON study (GT005-03) and the overall benefit-risk ratio did not support continuation of the current development program as planned. All GT005- treated subjects, who were willing to be transferred into the long-term safety follow-up study were enrolled in the ORACLE (CPPY988A12203B) study.
Interventions
DRUGGT005
GT005 is a recombinant, non-replicating AAV2 expressing human complement factor I (CFI). GT005 was administered as a single time subretinal injection into the study eye of subjects allocated to one of the two GT005 doses.
Sponsors
Gyroscope Therapeutics Limited
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Quadruple (Participant, Care Provider, Investigator, Outcome Assessor). The overall objectives of the study are to evaluate the safety and efficacy (anatomical and functional visual outcomes) of two doses of GT005 in genetically defined subjects with GA due to AMD.
Intervention model description
This is a Phase II, open-label, outcomes-assessor masked, multicentre, randomised, controlled study to evaluate the safety and efficacy of two doses of GT005 administered as a single subretinal injection in subjects with GA secondary to AMD.
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Able and willing to give written informed consent 2. Age ≥55 years 3. a. In Stage 1: Have a clinical diagnosis of GA secondary to AMD in the study eye, as determined by the Investigator, and a diagnosis of AMD in the contralateral eye; b. In Stage 2: Have a clinical diagnosis of GA secondary to AMD in the study eye, as determined by the Investigator, that is non-foveal, as determined by the central reading centre, or has a CFI rare variant genotype and meets inclusion criteria 3a, and a diagnosis of AMD in the contralateral eye (except if monocular) 4. GA lesion(s) within an acceptable size on FAF, in the study eye 5. The GA lesion in the study eye must reside completely within the FAF image 6. Up to 25% of the enrolled study population are permitted to have CNV in the fellow eye 7. Have a BCVA of ≥24 letters (6/95 or 20/320 Snellen acuity equivalent), using ETDRS charts, in the study eye 8. a. In Stage 1: Meet one of the pre-specified AMD genetic subgroup criteria; b. In Stage 2: Genotyping is not required for study eligibility 9. Able to attend all study visits and complete the study procedures 10. Women of child-bearing potential must have a negative pregnancy test within 2 weeks prior to randomisation (not required for postmenopausal women) or provide documentation of being surgically sterilised
Exclusion criteria
1. a. In Stage 1: Carriers of excluded genetic variants; b. In Stage 2: Subjects are excluded if they have a clinical diagnosis of Stargardt Disease or other retinal dystrophies 2. Have a history, or evidence, of CNV in the study eye 3. Presence of moderate/severe or worse non-proliferative, diabetic retinopathy in the study eye 4. Have history of vitrectomy, sub-macular surgery, or macular photocoagulation in the study eye 5. History of intraocular surgery in the study eye within 12 weeks prior to Visit 1 6. Have clinically significant cataract that may require surgery during the study period in the study eye 7. Presence of moderate to severe glaucomatous optic neuropathy, uncontrolled intraocular pressure (IOP), despite use of two or more topical agents; or a history of glaucoma-filtering or valve surgery 8. Axial myopia of greater than -8 diopters in the study eye 9. Have received any investigational product for the treatment of GA within the past 6 months or 5 half-lives (whichever is longer), other than nutritional supplements such as the age-related eye disease study (AREDS) formula 10. Have received a gene or cell therapy at any time. 11. Have a contraindication to the protocol specified corticosteroid regimen 12. Are unwilling to use two forms of contraception (one of which being a barrier method) for 90 days post-dosing, if relevant 13. Active malignancy within the past 12 months, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or prostate cancer with a stable prostate-specific antigen (PSA) ≥ 12 months 14. Have any other significant ocular or non-ocular medical or psychiatric condition which, in the opinion of the Investigator, may either put the subject at risk or may influence the results of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Change From Baseline to Week 72 in Geographic Atrophy (GA) | Baseline, Weeks 12, 24, 36, 48 and 72 | GA area as measured by fundus autofluorescence (FAF) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Change From Baseline at Week 96 in Geographic Atrophy (GA) | Baseline, Week 96 | GA area as measured by fundus autofluorescence (FAF) |
| Summary of Adverse Events | Adverse events are reported from randomization to the end of study, at Week 96, up to a maximum timeframe of approximately 96 weeks. | An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject. A TEAE is defined as any AE that develops after randomization or any AE already present that worsens following randomization. The primary summaries of AEs are based on TEAEs. |
| Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | Adverse events are reported from randomization to the end of study, at Week 96, up to a maximum timeframe of approximately 96 weeks. | An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject. A TEAE is defined as any AE that develops after randomization or any AE already present that worsens following randomization. The primary summaries of AEs are based on TEAEs. System organ classes are sorted alphabetically, and preferred terms are sorted by decreasing overall frequency within system organ class. |
| Non-ocular AEs Occurring in ≥2% of Subjects | Adverse events are reported from randomization to the end of study, at Week 96, up to a maximum timeframe of approximately 96 weeks. | An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject. A TEAE is defined as any AE that develops after randomization or any AE already present that worsens following randomization. The primary summaries of AEs are based on TEAEs. |
| Change in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence | Baseline, Weeks 5, 12, 24, 36, 48, 72 and 96 | Change in retinal morphology on multimodal imaging. For the untreated control group, there were no protocol-specified visits at Week 5. |
| Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Baseline, Weeks 1, 5, 8, 12, 24, 36, 48, 72 and 96 | BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning. For the untreated control group, there were no protocol-specified visits for Weeks 1, 5 and 8. |
| Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, 48, 72 and 96, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Baseline, Weeks 12, 24, 36, 48, 72 and 96 | LLD was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. The test was to be performed after BCVA testing, prior to pupil dilation, and distance refraction was to be carried out before Low Luminance Visual Acuity (LLVA) was measured. LLVA was to be measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the subject read the normally illuminated ETDRS chart. The LLD was calculated as the difference between BCVA and LLVA. Initially, letters were to be read at a distance of 4 metres from the chart. If \<20 letters were read at 4 metres, testing at 1 metre should have been performed. LLD was to be reported as number of letters read correctly by the subject. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning. |
| Reading Performance, Measured as the MRS (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart: Summary Statistics for Change From Baseline by Visit for the Study Eye | Baseline, Weeks 12, 24, 36, 48, 72 and 96 | The maximum reading speed (MRS) represents the highest reading speed an individual can achieve when print size is not a limiting factor. Essentially, it measures how quickly a person can read text when the print is large enough to be easily readable. A higher count represents better visual functioning. |
| Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index | Baseline, Weeks 24, 36, 48, 72 and 96 | The FRI index is a patient-reported outcome measure developed specifically for use in GA patients. The FRI index evaluates the level of independence subjects have in performing everyday activities that require reading, such as writing a cheque or reading a prescription. Scores derived from the index range from 1 (unable to do) to 4 (total independence). A higher score represents better visual functioning. |
| Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score | Baseline, Weeks 24, 36, 48, 72 and 96 | The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales. |
Countries
Australia, France, Germany, Poland, Spain, United Kingdom, United States
Participant flow
Recruitment details
This was a 3-arm study conducted in 2 stages. Results are reported per the 3 treatment arms. Stage 1 and Stage 2 results were combined since the study population and study treatments were the same in both Stage 1 and Stage 2; In Stage 1, participants were enrolled with both foveal and non-foveal geographic atrophy and in Stage 2, participants were enrolled with non-foveal geographic atrophy to enrich the number of participants with non-foveal geographic atrophy.
Pre-assignment details
The study design with 3 arms was the same for both Stage 1 and 2. Analysis was performed following the statistical analysis plan to combine Stage 1 and 2 results, and to report results per the 3 unique treatment arms.
Participants by arm
| Arm | Count |
|---|---|
| GT005 Medium Dose [5E10 vg] GT005 Medium dose \[5E10 vg\] | 87 |
| GT005 High Dose [2E11 vg] GT005 High dose \[2E11 vg\] | 86 |
| Untreated Control Untreated control | 82 |
| Total | 255 |
Baseline characteristics
| Characteristic | GT005 Medium Dose [5E10 vg] | GT005 High Dose [2E11 vg] | Untreated Control | Total |
|---|---|---|---|---|
| Age, Continuous | 77.6 Years STANDARD_DEVIATION 7.33 | 77.6 Years STANDARD_DEVIATION 7.6 | 77.8 Years STANDARD_DEVIATION 6.83 | 77.7 Years STANDARD_DEVIATION 7.24 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 5 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) White | 87 Participants | 80 Participants | 80 Participants | 247 Participants |
| Sex: Female, Male Female | 52 Participants | 61 Participants | 53 Participants | 166 Participants |
| Sex: Female, Male Male | 35 Participants | 25 Participants | 29 Participants | 89 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 87 | 1 / 86 | 1 / 82 | 6 / 255 |
| other Total, other adverse events | 76 / 87 | 75 / 86 | 50 / 82 | 201 / 255 |
| serious Total, serious adverse events | 22 / 87 | 25 / 86 | 10 / 82 | 57 / 255 |
Outcome results
Primary
The Change From Baseline to Week 72 in Geographic Atrophy (GA)
GA area as measured by fundus autofluorescence (FAF)
Time frame: Baseline, Weeks 12, 24, 36, 48 and 72
Population: Full Analysis Set - for participants with a valid measurement without a protocol deviation with impact.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| GT005 Medium Dose [5E10 vg] | The Change From Baseline to Week 72 in Geographic Atrophy (GA) | Week 24 (n=72,75,71) | 1.151 mm^2 | Standard Error 0.0833 |
| GT005 Medium Dose [5E10 vg] | The Change From Baseline to Week 72 in Geographic Atrophy (GA) | Week 12 (n=75,71,72) | 0.730 mm^2 | Standard Error 0.0625 |
| GT005 Medium Dose [5E10 vg] | The Change From Baseline to Week 72 in Geographic Atrophy (GA) | Week 36 (n=66,66,71) | 1.728 mm^2 | Standard Error 0.1488 |
| GT005 Medium Dose [5E10 vg] | The Change From Baseline to Week 72 in Geographic Atrophy (GA) | Week 72 (n=56,51,54) | 3.225 mm^2 | Standard Error 0.2337 |
| GT005 Medium Dose [5E10 vg] | The Change From Baseline to Week 72 in Geographic Atrophy (GA) | Week 48 (n=64,68,65) | 2.098 mm^2 | Standard Error 0.1841 |
| GT005 High Dose [2E11 vg] | The Change From Baseline to Week 72 in Geographic Atrophy (GA) | Week 72 (n=56,51,54) | 3.421 mm^2 | Standard Error 0.2369 |
| GT005 High Dose [2E11 vg] | The Change From Baseline to Week 72 in Geographic Atrophy (GA) | Week 12 (n=75,71,72) | 0.752 mm^2 | Standard Error 0.0634 |
| GT005 High Dose [2E11 vg] | The Change From Baseline to Week 72 in Geographic Atrophy (GA) | Week 24 (n=72,75,71) | 1.260 mm^2 | Standard Error 0.0831 |
| GT005 High Dose [2E11 vg] | The Change From Baseline to Week 72 in Geographic Atrophy (GA) | Week 36 (n=66,66,71) | 1.955 mm^2 | Standard Error 0.1503 |
| GT005 High Dose [2E11 vg] | The Change From Baseline to Week 72 in Geographic Atrophy (GA) | Week 48 (n=64,68,65) | 2.535 mm^2 | Standard Error 0.1853 |
| Untreated Control | The Change From Baseline to Week 72 in Geographic Atrophy (GA) | Week 36 (n=66,66,71) | 1.531 mm^2 | Standard Error 0.1528 |
| Untreated Control | The Change From Baseline to Week 72 in Geographic Atrophy (GA) | Week 12 (n=75,71,72) | 0.667 mm^2 | Standard Error 0.0647 |
| Untreated Control | The Change From Baseline to Week 72 in Geographic Atrophy (GA) | Week 72 (n=56,51,54) | 2.919 mm^2 | Standard Error 0.2412 |
| Untreated Control | The Change From Baseline to Week 72 in Geographic Atrophy (GA) | Week 24 (n=72,75,71) | 1.054 mm^2 | Standard Error 0.086 |
| Untreated Control | The Change From Baseline to Week 72 in Geographic Atrophy (GA) | Week 48 (n=64,68,65) | 2.047 mm^2 | Standard Error 0.1896 |
Comparison: Week 1290% CI: [-0.087, 0.211]mixed model repeated measures
Comparison: Week 1290% CI: [-0.066, 0.234]mixed model repeated measures
Comparison: Week 2490% CI: [-0.102, 0.294]mixed model repeated measures
Comparison: Week 2490% CI: [0.007, 0.404]mixed model repeated measures
Comparison: Week 3690% CI: [-0.155, 0.55]mixed model repeated measures
Comparison: Week 3690% CI: [0.068, 0.779]mixed model repeated measures
Comparison: Week 4890% CI: [-0.385, 0.489]mixed model repeated measures
Comparison: Week 4890% CI: [0.049, 0.928]mixed model repeated measures
Comparison: Week 7290% CI: [-0.248, 0.862]mixed model repeated measures
Comparison: Week 7290% CI: [-0.058, 1.063]mixed model repeated measures
Secondary
Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index
The FRI index is a patient-reported outcome measure developed specifically for use in GA patients. The FRI index evaluates the level of independence subjects have in performing everyday activities that require reading, such as writing a cheque or reading a prescription. Scores derived from the index range from 1 (unable to do) to 4 (total independence). A higher score represents better visual functioning.
Time frame: Baseline, Weeks 24, 36, 48, 72 and 96
Population: Full Analysis Set - for participants with a valid measurement without a protocol deviation with impact.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GT005 Medium Dose [5E10 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index | Week 72 (n=63,69,58) | -0.8 Scores on a scale | Standard Deviation 4.93 |
| GT005 Medium Dose [5E10 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index | Week 24 (n=77,75,67) | -0.4 Scores on a scale | Standard Deviation 5.2 |
| GT005 Medium Dose [5E10 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index | Week 36 (n=74,72,66) | -0.8 Scores on a scale | Standard Deviation 4.64 |
| GT005 Medium Dose [5E10 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index | Week 48 (n=70,73,65) | -0.3 Scores on a scale | Standard Deviation 4.76 |
| GT005 Medium Dose [5E10 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index | Week 96 (n=54,51,32) | -1.4 Scores on a scale | Standard Deviation 5.57 |
| GT005 High Dose [2E11 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index | Week 36 (n=74,72,66) | -1.1 Scores on a scale | Standard Deviation 4.31 |
| GT005 High Dose [2E11 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index | Week 96 (n=54,51,32) | -1.4 Scores on a scale | Standard Deviation 4.41 |
| GT005 High Dose [2E11 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index | Week 48 (n=70,73,65) | -1.4 Scores on a scale | Standard Deviation 4.87 |
| GT005 High Dose [2E11 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index | Week 72 (n=63,69,58) | -1.3 Scores on a scale | Standard Deviation 5.19 |
| GT005 High Dose [2E11 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index | Week 24 (n=77,75,67) | -1.4 Scores on a scale | Standard Deviation 4.74 |
| Untreated Control | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index | Week 24 (n=77,75,67) | -0.1 Scores on a scale | Standard Deviation 3.98 |
| Untreated Control | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index | Week 36 (n=74,72,66) | -0.1 Scores on a scale | Standard Deviation 4.67 |
| Untreated Control | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index | Week 72 (n=63,69,58) | -1.5 Scores on a scale | Standard Deviation 5.37 |
| Untreated Control | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index | Week 96 (n=54,51,32) | -1.1 Scores on a scale | Standard Deviation 5.11 |
| Untreated Control | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index | Week 48 (n=70,73,65) | -0.2 Scores on a scale | Standard Deviation 4.5 |
Secondary
Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
Time frame: Baseline, Weeks 24, 36, 48, 72 and 96
Population: Full Analysis Set - for participants with a valid measurement without a protocol deviation with impact.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GT005 Medium Dose [5E10 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score | Week 72 (n=63,69,54) | -4.232 Scores on a scale | Standard Deviation 14.6259 |
| GT005 Medium Dose [5E10 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score | Week 48 (n=70,74,65) | -2.501 Scores on a scale | Standard Deviation 12.9563 |
| GT005 Medium Dose [5E10 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score | Week 24 (n=77,78,67) | -1.466 Scores on a scale | Standard Deviation 12.8742 |
| GT005 Medium Dose [5E10 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score | Week 36 (n=74,73,66) | -1.955 Scores on a scale | Standard Deviation 11.506 |
| GT005 Medium Dose [5E10 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score | Week 96 (n=54,51,33) | -6.341 Scores on a scale | Standard Deviation 14.4187 |
| GT005 High Dose [2E11 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score | Week 48 (n=70,74,65) | -3.113 Scores on a scale | Standard Deviation 11.9974 |
| GT005 High Dose [2E11 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score | Week 24 (n=77,78,67) | -2.289 Scores on a scale | Standard Deviation 12.3295 |
| GT005 High Dose [2E11 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score | Week 36 (n=74,73,66) | -3.479 Scores on a scale | Standard Deviation 12.0848 |
| GT005 High Dose [2E11 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score | Week 72 (n=63,69,54) | -3.432 Scores on a scale | Standard Deviation 11.384 |
| GT005 High Dose [2E11 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score | Week 96 (n=54,51,33) | -7.718 Scores on a scale | Standard Deviation 10.9016 |
| Untreated Control | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score | Week 96 (n=54,51,33) | -6.804 Scores on a scale | Standard Deviation 15.4812 |
| Untreated Control | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score | Week 72 (n=63,69,54) | -6.583 Scores on a scale | Standard Deviation 15.5133 |
| Untreated Control | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score | Week 24 (n=77,78,67) | -1.270 Scores on a scale | Standard Deviation 11.2063 |
| Untreated Control | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score | Week 48 (n=70,74,65) | -4.403 Scores on a scale | Standard Deviation 14.2465 |
| Untreated Control | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score | Week 36 (n=74,73,66) | -2.273 Scores on a scale | Standard Deviation 12.2395 |
Secondary
Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart
BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning. For the untreated control group, there were no protocol-specified visits for Weeks 1, 5 and 8.
Time frame: Baseline, Weeks 1, 5, 8, 12, 24, 36, 48, 72 and 96
Population: Full Analysis Set - for participants with a valid measurement without a protocol deviation with impact.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| GT005 Medium Dose [5E10 vg] | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 1 (n=81,78,0) | -2.0 Letters read | Standard Error 1.54 |
| GT005 Medium Dose [5E10 vg] | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 5 (n=81,78,0) | -0.8 Letters read | Standard Error 0.88 |
| GT005 Medium Dose [5E10 vg] | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 8 (n=79,77,0) | -0.1 Letters read | Standard Error 0.85 |
| GT005 Medium Dose [5E10 vg] | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 12 (n=79,79,73) | -1.1 Letters read | Standard Error 0.91 |
| GT005 Medium Dose [5E10 vg] | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 24 (n=78,78,71) | -2.7 Letters read | Standard Error 1.03 |
| GT005 Medium Dose [5E10 vg] | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 36 (75,74,72) | -2.5 Letters read | Standard Error 1.24 |
| GT005 Medium Dose [5E10 vg] | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 48 (n=73,75,69) | -2.6 Letters read | Standard Error 1.48 |
| GT005 Medium Dose [5E10 vg] | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 72 (n=63, 70, 58) | -4.1 Letters read | Standard Error 1.54 |
| GT005 Medium Dose [5E10 vg] | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 96 (n=54,51,35) | -5.5 Letters read | Standard Error 1.78 |
| GT005 High Dose [2E11 vg] | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 72 (n=63, 70, 58) | -7.9 Letters read | Standard Error 1.5 |
| GT005 High Dose [2E11 vg] | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 24 (n=78,78,71) | -6.3 Letters read | Standard Error 1.03 |
| GT005 High Dose [2E11 vg] | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 1 (n=81,78,0) | -7.0 Letters read | Standard Error 1.56 |
| GT005 High Dose [2E11 vg] | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 48 (n=73,75,69) | -7.3 Letters read | Standard Error 1.46 |
| GT005 High Dose [2E11 vg] | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 5 (n=81,78,0) | -3.3 Letters read | Standard Error 0.89 |
| GT005 High Dose [2E11 vg] | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 8 (n=79,77,0) | -1.7 Letters read | Standard Error 0.86 |
| GT005 High Dose [2E11 vg] | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 96 (n=54,51,35) | -10.0 Letters read | Standard Error 1.78 |
| GT005 High Dose [2E11 vg] | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 12 (n=79,79,73) | -2.5 Letters read | Standard Error 0.91 |
| GT005 High Dose [2E11 vg] | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 36 (75,74,72) | -7.7 Letters read | Standard Error 1.25 |
| Untreated Control | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 24 (n=78,78,71) | -1.1 Letters read | Standard Error 1.09 |
| Untreated Control | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 72 (n=63, 70, 58) | -8.8 Letters read | Standard Error 1.61 |
| Untreated Control | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 48 (n=73,75,69) | -5.3 Letters read | Standard Error 1.54 |
| Untreated Control | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 36 (75,74,72) | -3.0 Letters read | Standard Error 1.3 |
| Untreated Control | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 96 (n=54,51,35) | -12.7 Letters read | Standard Error 2.02 |
| Untreated Control | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 12 (n=79,79,73) | -0.7 Letters read | Standard Error 0.96 |
Comparison: Week 1290% CI: [-2.6, 1.7]mixed model repeated measures
Comparison: Week 1290% CI: [-4, 0.4]mixed model repeated measures
Comparison: Week 2490% CI: [-4.1, 0.8]mixed model repeated measures
Comparison: Week 2490% CI: [-7.7, -2.8]mixed model repeated measures
Comparison: Week 3690% CI: [-2.5, 3.5]mixed model repeated measures
Comparison: Week 3690% CI: [-7.7, -1.7]mixed model repeated measures
Comparison: Week 4890% CI: [-0.9, 6.1]mixed model repeated measures
Comparison: Week 4890% CI: [-5.6, 1.4]mixed model repeated measures
Comparison: Week 7290% CI: [1, 8.4]mixed model repeated measures
Comparison: Week 7290% CI: [-2.8, 4.5]mixed model repeated measures
Comparison: Week 9690% CI: [2.7, 11.6]mixed model repeated measures
Comparison: Week 9690% CI: [-1.8, 7.1]mixed model repeated measures
Secondary
Change in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence
Change in retinal morphology on multimodal imaging. For the untreated control group, there were no protocol-specified visits at Week 5.
Time frame: Baseline, Weeks 5, 12, 24, 36, 48, 72 and 96
Population: Full Analysis Set - for participants with a valid measurement without a protocol deviation with impact.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GT005 Medium Dose [5E10 vg] | Change in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence | Week 72 (n=61, 62,59) | 60 Participants |
| GT005 Medium Dose [5E10 vg] | Change in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence | Week 24 (n=75,78,72) | 72 Participants |
| GT005 Medium Dose [5E10 vg] | Change in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence | Week 96 (n=52,49, 34) | 50 Participants |
| GT005 Medium Dose [5E10 vg] | Change in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence | Week 5 (n=23,24,0) | 23 Participants |
| GT005 Medium Dose [5E10 vg] | Change in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence | Week 12 (n=75,73,74) | 74 Participants |
| GT005 Medium Dose [5E10 vg] | Change in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence | Week 36 (n=70,70, 71) | 66 Participants |
| GT005 Medium Dose [5E10 vg] | Change in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence | Week 48 (n=67,72,68) | 67 Participants |
| GT005 High Dose [2E11 vg] | Change in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence | Week 5 (n=23,24,0) | 23 Participants |
| GT005 High Dose [2E11 vg] | Change in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence | Week 72 (n=61, 62,59) | 60 Participants |
| GT005 High Dose [2E11 vg] | Change in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence | Week 48 (n=67,72,68) | 71 Participants |
| GT005 High Dose [2E11 vg] | Change in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence | Week 36 (n=70,70, 71) | 69 Participants |
| GT005 High Dose [2E11 vg] | Change in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence | Week 96 (n=52,49, 34) | 48 Participants |
| GT005 High Dose [2E11 vg] | Change in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence | Week 12 (n=75,73,74) | 73 Participants |
| GT005 High Dose [2E11 vg] | Change in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence | Week 24 (n=75,78,72) | 78 Participants |
| Untreated Control | Change in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence | Week 96 (n=52,49, 34) | 33 Participants |
| Untreated Control | Change in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence | Week 12 (n=75,73,74) | 73 Participants |
| Untreated Control | Change in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence | Week 24 (n=75,78,72) | 71 Participants |
| Untreated Control | Change in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence | Week 36 (n=70,70, 71) | 70 Participants |
| Untreated Control | Change in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence | Week 48 (n=67,72,68) | 68 Participants |
| Untreated Control | Change in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence | Week 72 (n=61, 62,59) | 56 Participants |
Secondary
Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, 48, 72 and 96, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart
LLD was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. The test was to be performed after BCVA testing, prior to pupil dilation, and distance refraction was to be carried out before Low Luminance Visual Acuity (LLVA) was measured. LLVA was to be measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the subject read the normally illuminated ETDRS chart. The LLD was calculated as the difference between BCVA and LLVA. Initially, letters were to be read at a distance of 4 metres from the chart. If \<20 letters were read at 4 metres, testing at 1 metre should have been performed. LLD was to be reported as number of letters read correctly by the subject. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
Time frame: Baseline, Weeks 12, 24, 36, 48, 72 and 96
Population: Full Analysis Set - for participants with a valid measurement without a protocol deviation with impact.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GT005 Medium Dose [5E10 vg] | Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, 48, 72 and 96, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 12 | -0.6 Letters read | Standard Deviation 7.59 |
| GT005 Medium Dose [5E10 vg] | Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, 48, 72 and 96, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 24 (n=78,75,71) | -0.6 Letters read | Standard Deviation 10.1 |
| GT005 Medium Dose [5E10 vg] | Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, 48, 72 and 96, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 36 (n=75,72,71) | 0.0 Letters read | Standard Deviation 9.9 |
| GT005 Medium Dose [5E10 vg] | Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, 48, 72 and 96, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 48 (n=73,73,69) | -0.5 Letters read | Standard Deviation 10.31 |
| GT005 Medium Dose [5E10 vg] | Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, 48, 72 and 96, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 72 (n=63,67,58) | -0.5 Letters read | Standard Deviation 13.15 |
| GT005 Medium Dose [5E10 vg] | Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, 48, 72 and 96, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 96 (n=54,49,35) | -3.1 Letters read | Standard Deviation 16.11 |
| GT005 High Dose [2E11 vg] | Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, 48, 72 and 96, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 96 (n=54,49,35) | -2.2 Letters read | Standard Deviation 13.48 |
| GT005 High Dose [2E11 vg] | Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, 48, 72 and 96, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 12 | -1.1 Letters read | Standard Deviation 9.63 |
| GT005 High Dose [2E11 vg] | Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, 48, 72 and 96, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 48 (n=73,73,69) | -1.5 Letters read | Standard Deviation 15.18 |
| GT005 High Dose [2E11 vg] | Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, 48, 72 and 96, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 72 (n=63,67,58) | -5.2 Letters read | Standard Deviation 17.24 |
| GT005 High Dose [2E11 vg] | Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, 48, 72 and 96, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 24 (n=78,75,71) | -2.5 Letters read | Standard Deviation 12.73 |
| GT005 High Dose [2E11 vg] | Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, 48, 72 and 96, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 36 (n=75,72,71) | -2.6 Letters read | Standard Deviation 13.4 |
| Untreated Control | Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, 48, 72 and 96, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 24 (n=78,75,71) | 0.5 Letters read | Standard Deviation 12.01 |
| Untreated Control | Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, 48, 72 and 96, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 36 (n=75,72,71) | -0.1 Letters read | Standard Deviation 11.12 |
| Untreated Control | Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, 48, 72 and 96, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 96 (n=54,49,35) | -5.9 Letters read | Standard Deviation 16.82 |
| Untreated Control | Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, 48, 72 and 96, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 48 (n=73,73,69) | -0.4 Letters read | Standard Deviation 12.93 |
| Untreated Control | Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, 48, 72 and 96, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 12 | 1.2 Letters read | Standard Deviation 9.51 |
| Untreated Control | Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, 48, 72 and 96, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart | Week 72 (n=63,67,58) | -2.5 Letters read | Standard Deviation 14.93 |
Secondary
Non-ocular AEs Occurring in ≥2% of Subjects
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject. A TEAE is defined as any AE that develops after randomization or any AE already present that worsens following randomization. The primary summaries of AEs are based on TEAEs.
Time frame: Adverse events are reported from randomization to the end of study, at Week 96, up to a maximum timeframe of approximately 96 weeks.
Population: Full Analysis Set - all randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GT005 Medium Dose [5E10 vg] | Non-ocular AEs Occurring in ≥2% of Subjects | 63 Participants |
| GT005 High Dose [2E11 vg] | Non-ocular AEs Occurring in ≥2% of Subjects | 59 Participants |
| Untreated Control | Non-ocular AEs Occurring in ≥2% of Subjects | 44 Participants |
Secondary
Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject. A TEAE is defined as any AE that develops after randomization or any AE already present that worsens following randomization. The primary summaries of AEs are based on TEAEs. System organ classes are sorted alphabetically, and preferred terms are sorted by decreasing overall frequency within system organ class.
Time frame: Adverse events are reported from randomization to the end of study, at Week 96, up to a maximum timeframe of approximately 96 weeks.
Population: Full Analysis Set - all randomized participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GT005 Medium Dose [5E10 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Retinal tear | 5 Participants |
| GT005 Medium Dose [5E10 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Intraocular pressure increased | 1 Participants |
| GT005 Medium Dose [5E10 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Retinal detachment | 2 Participants |
| GT005 Medium Dose [5E10 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Dry eye | 4 Participants |
| GT005 Medium Dose [5E10 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | Subjects with at least one event | 66 Participants |
| GT005 Medium Dose [5E10 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Cataract nuclear | 3 Participants |
| GT005 Medium Dose [5E10 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Posterior capsule opacification | 3 Participants |
| GT005 Medium Dose [5E10 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Conjunctival haemorrhage | 18 Participants |
| GT005 Medium Dose [5E10 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Vitreous floaters | 3 Participants |
| GT005 Medium Dose [5E10 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Anterior chamber cell | 4 Participants |
| GT005 Medium Dose [5E10 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | Investigations | 11 Participants |
| GT005 Medium Dose [5E10 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Choroidal neovascularisation | 2 Participants |
| GT005 Medium Dose [5E10 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Eye irritation | 6 Participants |
| GT005 Medium Dose [5E10 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Iritis | 4 Participants |
| GT005 Medium Dose [5E10 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Vitreous haemorrhage | 2 Participants |
| GT005 Medium Dose [5E10 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Retinal haemorrhage | 8 Participants |
| GT005 Medium Dose [5E10 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Cataract | 21 Participants |
| GT005 Medium Dose [5E10 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Foreign body sensation in eyes | 3 Participants |
| GT005 Medium Dose [5E10 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Eye pain | 5 Participants |
| GT005 Medium Dose [5E10 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | Eye disorders | 65 Participants |
| GT005 Medium Dose [5E10 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Eye pruritus | 1 Participants |
| GT005 Medium Dose [5E10 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Ocular hypertension | 6 Participants |
| GT005 Medium Dose [5E10 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Visual impairment | 2 Participants |
| GT005 Medium Dose [5E10 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Diplopia | 4 Participants |
| GT005 Medium Dose [5E10 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Punctate keratitis | 6 Participants |
| GT005 Medium Dose [5E10 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Retinal pigmentation | 12 Participants |
| GT005 Medium Dose [5E10 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Corneal oedema | 1 Participants |
| GT005 High Dose [2E11 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Iritis | 1 Participants |
| GT005 High Dose [2E11 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | Subjects with at least one event | 65 Participants |
| GT005 High Dose [2E11 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | Eye disorders | 62 Participants |
| GT005 High Dose [2E11 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Cataract | 20 Participants |
| GT005 High Dose [2E11 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Retinal pigmentation | 22 Participants |
| GT005 High Dose [2E11 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Conjunctival haemorrhage | 12 Participants |
| GT005 High Dose [2E11 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Retinal haemorrhage | 10 Participants |
| GT005 High Dose [2E11 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Eye pain | 7 Participants |
| GT005 High Dose [2E11 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Ocular hypertension | 6 Participants |
| GT005 High Dose [2E11 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Punctate keratitis | 6 Participants |
| GT005 High Dose [2E11 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Retinal tear | 6 Participants |
| GT005 High Dose [2E11 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Dry eye | 4 Participants |
| GT005 High Dose [2E11 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Posterior capsule opacification | 4 Participants |
| GT005 High Dose [2E11 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Anterior chamber cell | 4 Participants |
| GT005 High Dose [2E11 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Eye irritation | 2 Participants |
| GT005 High Dose [2E11 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Vitreous haemorrhage | 6 Participants |
| GT005 High Dose [2E11 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Choroidal neovascularisation | 3 Participants |
| GT005 High Dose [2E11 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Vitreous floaters | 4 Participants |
| GT005 High Dose [2E11 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Cataract nuclear | 3 Participants |
| GT005 High Dose [2E11 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Retinal detachment | 4 Participants |
| GT005 High Dose [2E11 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Corneal oedema | 4 Participants |
| GT005 High Dose [2E11 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Diplopia | 1 Participants |
| GT005 High Dose [2E11 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Eye pruritus | 4 Participants |
| GT005 High Dose [2E11 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Foreign body sensation in eyes | 2 Participants |
| GT005 High Dose [2E11 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Visual impairment | 3 Participants |
| GT005 High Dose [2E11 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | Investigations | 2 Participants |
| GT005 High Dose [2E11 vg] | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Intraocular pressure increased | 2 Participants |
| Untreated Control | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Retinal tear | 0 Participants |
| Untreated Control | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | Subjects with at least one event | 15 Participants |
| Untreated Control | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Retinal detachment | 0 Participants |
| Untreated Control | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Punctate keratitis | 0 Participants |
| Untreated Control | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Visual impairment | 0 Participants |
| Untreated Control | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Corneal oedema | 0 Participants |
| Untreated Control | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Ocular hypertension | 0 Participants |
| Untreated Control | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | Eye disorders | 14 Participants |
| Untreated Control | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Diplopia | 0 Participants |
| Untreated Control | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Eye pain | 0 Participants |
| Untreated Control | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Intraocular pressure increased | 0 Participants |
| Untreated Control | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Eye pruritus | 0 Participants |
| Untreated Control | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Retinal haemorrhage | 2 Participants |
| Untreated Control | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | Investigations | 0 Participants |
| Untreated Control | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Foreign body sensation in eyes | 0 Participants |
| Untreated Control | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Eye irritation | 0 Participants |
| Untreated Control | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Conjunctival haemorrhage | 1 Participants |
| Untreated Control | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Vitreous haemorrhage | 0 Participants |
| Untreated Control | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Anterior chamber cell | 0 Participants |
| Untreated Control | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Retinal pigmentation | 0 Participants |
| Untreated Control | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Choroidal neovascularisation | 2 Participants |
| Untreated Control | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Posterior capsule opacification | 2 Participants |
| Untreated Control | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Iritis | 0 Participants |
| Untreated Control | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Vitreous floaters | 0 Participants |
| Untreated Control | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Dry eye | 1 Participants |
| Untreated Control | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Cataract | 3 Participants |
| Untreated Control | Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye | -Cataract nuclear | 0 Participants |
Secondary
Reading Performance, Measured as the MRS (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart: Summary Statistics for Change From Baseline by Visit for the Study Eye
The maximum reading speed (MRS) represents the highest reading speed an individual can achieve when print size is not a limiting factor. Essentially, it measures how quickly a person can read text when the print is large enough to be easily readable. A higher count represents better visual functioning.
Time frame: Baseline, Weeks 12, 24, 36, 48, 72 and 96
Population: Full Analysis Set - for participants with a valid measurement without a protocol deviation with impact.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GT005 Medium Dose [5E10 vg] | Reading Performance, Measured as the MRS (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart: Summary Statistics for Change From Baseline by Visit for the Study Eye | Week 72 (n=57,64,53) | -24.485 Words read per minute | Standard Deviation 45.8525 |
| GT005 Medium Dose [5E10 vg] | Reading Performance, Measured as the MRS (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart: Summary Statistics for Change From Baseline by Visit for the Study Eye | Week 48 (n=69,67,62) | -20.734 Words read per minute | Standard Deviation 36.411 |
| GT005 Medium Dose [5E10 vg] | Reading Performance, Measured as the MRS (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart: Summary Statistics for Change From Baseline by Visit for the Study Eye | Week 24 (n=73,72,65) | -15.756 Words read per minute | Standard Deviation 32.7268 |
| GT005 Medium Dose [5E10 vg] | Reading Performance, Measured as the MRS (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart: Summary Statistics for Change From Baseline by Visit for the Study Eye | Week 36 (n=71,70,65) | -18.488 Words read per minute | Standard Deviation 54.7913 |
| GT005 Medium Dose [5E10 vg] | Reading Performance, Measured as the MRS (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart: Summary Statistics for Change From Baseline by Visit for the Study Eye | Week 96 (n=48,47,29) | -24.678 Words read per minute | Standard Deviation 44.7777 |
| GT005 High Dose [2E11 vg] | Reading Performance, Measured as the MRS (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart: Summary Statistics for Change From Baseline by Visit for the Study Eye | Week 48 (n=69,67,62) | -6.678 Words read per minute | Standard Deviation 49.0844 |
| GT005 High Dose [2E11 vg] | Reading Performance, Measured as the MRS (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart: Summary Statistics for Change From Baseline by Visit for the Study Eye | Week 24 (n=73,72,65) | -12.368 Words read per minute | Standard Deviation 43.2054 |
| GT005 High Dose [2E11 vg] | Reading Performance, Measured as the MRS (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart: Summary Statistics for Change From Baseline by Visit for the Study Eye | Week 36 (n=71,70,65) | -15.673 Words read per minute | Standard Deviation 31.7802 |
| GT005 High Dose [2E11 vg] | Reading Performance, Measured as the MRS (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart: Summary Statistics for Change From Baseline by Visit for the Study Eye | Week 72 (n=57,64,53) | -20.798 Words read per minute | Standard Deviation 39.6796 |
| GT005 High Dose [2E11 vg] | Reading Performance, Measured as the MRS (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart: Summary Statistics for Change From Baseline by Visit for the Study Eye | Week 96 (n=48,47,29) | -25.178 Words read per minute | Standard Deviation 39.7216 |
| Untreated Control | Reading Performance, Measured as the MRS (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart: Summary Statistics for Change From Baseline by Visit for the Study Eye | Week 96 (n=48,47,29) | -19.242 Words read per minute | Standard Deviation 45.0703 |
| Untreated Control | Reading Performance, Measured as the MRS (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart: Summary Statistics for Change From Baseline by Visit for the Study Eye | Week 72 (n=57,64,53) | -26.121 Words read per minute | Standard Deviation 40.8016 |
| Untreated Control | Reading Performance, Measured as the MRS (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart: Summary Statistics for Change From Baseline by Visit for the Study Eye | Week 24 (n=73,72,65) | -15.769 Words read per minute | Standard Deviation 40.5051 |
| Untreated Control | Reading Performance, Measured as the MRS (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart: Summary Statistics for Change From Baseline by Visit for the Study Eye | Week 48 (n=69,67,62) | -17.297 Words read per minute | Standard Deviation 56.8547 |
| Untreated Control | Reading Performance, Measured as the MRS (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart: Summary Statistics for Change From Baseline by Visit for the Study Eye | Week 36 (n=71,70,65) | -3.689 Words read per minute | Standard Deviation 94.1057 |
Secondary
Summary of Adverse Events
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject. A TEAE is defined as any AE that develops after randomization or any AE already present that worsens following randomization. The primary summaries of AEs are based on TEAEs.
Time frame: Adverse events are reported from randomization to the end of study, at Week 96, up to a maximum timeframe of approximately 96 weeks.
Population: Full Analysis Set - all randomized participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GT005 Medium Dose [5E10 vg] | Summary of Adverse Events | Subjects with at least one ocular adverse event for the study eye | 66 Participants |
| GT005 Medium Dose [5E10 vg] | Summary of Adverse Events | Deaths | 4 Participants |
| GT005 Medium Dose [5E10 vg] | Summary of Adverse Events | Subjects with at least one non-ocular adverse event related to study procedure | 0 Participants |
| GT005 Medium Dose [5E10 vg] | Summary of Adverse Events | Subjects with at least one ocular adverse event for the fellow eye | 32 Participants |
| GT005 Medium Dose [5E10 vg] | Summary of Adverse Events | Subjects with at least one ocular serious adverse event for the fellow eye | 0 Participants |
| GT005 Medium Dose [5E10 vg] | Summary of Adverse Events | Subjects with at least one ocular adverse event related to study procedure for the study eye | 8 Participants |
| GT005 Medium Dose [5E10 vg] | Summary of Adverse Events | Subjects with at least one non-ocular adverse event | 63 Participants |
| GT005 Medium Dose [5E10 vg] | Summary of Adverse Events | Subjects with at least one ocular serious adverse event related to study procedure for the study eye | 1 Participants |
| GT005 Medium Dose [5E10 vg] | Summary of Adverse Events | Subjects with at least one non-ocular adverse event related to surgical procedure | 0 Participants |
| GT005 Medium Dose [5E10 vg] | Summary of Adverse Events | Subjects with at least one ocular adverse event related to study treatment for the study eye | 13 Participants |
| GT005 Medium Dose [5E10 vg] | Summary of Adverse Events | Subjects with at least one ocular serious adverse event related to study treatment for the study eye | 0 Participants |
| GT005 Medium Dose [5E10 vg] | Summary of Adverse Events | Subjects with at least one ocular adverse event related to surgical procedure for the study eye | 48 Participants |
| GT005 Medium Dose [5E10 vg] | Summary of Adverse Events | Subjects with at least one non-ocular adverse event related to study treatment | 0 Participants |
| GT005 Medium Dose [5E10 vg] | Summary of Adverse Events | Subjects with at least one ocular serious adverse event (SAE) for the study eye | 2 Participants |
| GT005 Medium Dose [5E10 vg] | Summary of Adverse Events | Subjects with at least one non-ocular serious adverse event related to study procedure | 0 Participants |
| GT005 Medium Dose [5E10 vg] | Summary of Adverse Events | Subjects with at least one ocular SAE related to surgical procedure for the study eye | 1 Participants |
| GT005 Medium Dose [5E10 vg] | Summary of Adverse Events | Subjects with at least one ocular adverse event of special interest for the fellow eye | 3 Participants |
| GT005 Medium Dose [5E10 vg] | Summary of Adverse Events | Subjects with at least one ocular SAE leading to study discontinuation for the study eye | 0 Participants |
| GT005 Medium Dose [5E10 vg] | Summary of Adverse Events | Subjects with at least one non-ocular serious adverse event related to study treatment | 0 Participants |
| GT005 Medium Dose [5E10 vg] | Summary of Adverse Events | Subjects with at least one ocular adverse event of special interest for the study eye | 19 Participants |
| GT005 Medium Dose [5E10 vg] | Summary of Adverse Events | Subjects with at least one non-ocular serious adverse event leading to study discontinuation | 5 Participants |
| GT005 Medium Dose [5E10 vg] | Summary of Adverse Events | Subjects with at least one non-ocular serious adverse event | 20 Participants |
| GT005 Medium Dose [5E10 vg] | Summary of Adverse Events | Subjects with at least one non-ocular adverse event leading to study discontinuation | 5 Participants |
| GT005 Medium Dose [5E10 vg] | Summary of Adverse Events | Subjects with at least one non-ocular serious adverse event related to surgical procedure | 0 Participants |
| GT005 Medium Dose [5E10 vg] | Summary of Adverse Events | Subjects with at least one ocular adverse event leading to study discontinuation for the study eye | 0 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events | Subjects with at least one ocular serious adverse event related to study treatment for the study eye | 0 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events | Subjects with at least one non-ocular serious adverse event related to study treatment | 0 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events | Subjects with at least one ocular SAE related to surgical procedure for the study eye | 4 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events | Subjects with at least one non-ocular serious adverse event related to surgical procedure | 0 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events | Subjects with at least one ocular serious adverse event related to study procedure for the study eye | 1 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events | Subjects with at least one non-ocular serious adverse event related to study procedure | 0 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events | Subjects with at least one ocular SAE leading to study discontinuation for the study eye | 0 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events | Subjects with at least one non-ocular serious adverse event leading to study discontinuation | 2 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events | Deaths | 1 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events | Subjects with at least one ocular adverse event for the study eye | 65 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events | Subjects with at least one ocular adverse event for the fellow eye | 35 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events | Subjects with at least one non-ocular adverse event | 59 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events | Subjects with at least one ocular adverse event related to study treatment for the study eye | 21 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events | Subjects with at least one non-ocular adverse event related to study treatment | 0 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events | Subjects with at least one ocular adverse event related to surgical procedure for the study eye | 48 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events | Subjects with at least one non-ocular adverse event related to surgical procedure | 0 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events | Subjects with at least one ocular adverse event related to study procedure for the study eye | 9 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events | Subjects with at least one non-ocular adverse event related to study procedure | 2 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events | Subjects with at least one ocular adverse event leading to study discontinuation for the study eye | 0 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events | Subjects with at least one non-ocular adverse event leading to study discontinuation | 2 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events | Subjects with at least one ocular adverse event of special interest for the study eye | 31 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events | Subjects with at least one ocular adverse event of special interest for the fellow eye | 3 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events | Subjects with at least one ocular serious adverse event (SAE) for the study eye | 5 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events | Subjects with at least one ocular serious adverse event for the fellow eye | 0 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events | Subjects with at least one non-ocular serious adverse event | 22 Participants |
| Untreated Control | Summary of Adverse Events | Subjects with at least one non-ocular serious adverse event related to surgical procedure | 0 Participants |
| Untreated Control | Summary of Adverse Events | Subjects with at least one non-ocular adverse event related to study procedure | 0 Participants |
| Untreated Control | Summary of Adverse Events | Deaths | 1 Participants |
| Untreated Control | Summary of Adverse Events | Subjects with at least one non-ocular serious adverse event related to study treatment | 0 Participants |
| Untreated Control | Summary of Adverse Events | Subjects with at least one ocular adverse event leading to study discontinuation for the study eye | 0 Participants |
| Untreated Control | Summary of Adverse Events | Subjects with at least one non-ocular serious adverse event leading to study discontinuation | 1 Participants |
| Untreated Control | Summary of Adverse Events | Subjects with at least one ocular serious adverse event for the fellow eye | 0 Participants |
| Untreated Control | Summary of Adverse Events | Subjects with at least one non-ocular adverse event leading to study discontinuation | 1 Participants |
| Untreated Control | Summary of Adverse Events | Subjects with at least one ocular SAE leading to study discontinuation for the study eye | 0 Participants |
| Untreated Control | Summary of Adverse Events | Subjects with at least one ocular SAE related to surgical procedure for the study eye | 0 Participants |
| Untreated Control | Summary of Adverse Events | Subjects with at least one ocular adverse event of special interest for the study eye | 3 Participants |
| Untreated Control | Summary of Adverse Events | Subjects with at least one non-ocular serious adverse event related to study procedure | 0 Participants |
| Untreated Control | Summary of Adverse Events | Subjects with at least one ocular serious adverse event related to study treatment for the study eye | 0 Participants |
| Untreated Control | Summary of Adverse Events | Subjects with at least one ocular adverse event of special interest for the fellow eye | 1 Participants |
| Untreated Control | Summary of Adverse Events | Subjects with at least one non-ocular adverse event related to study treatment | 0 Participants |
| Untreated Control | Summary of Adverse Events | Subjects with at least one ocular adverse event related to study treatment for the study eye | 0 Participants |
| Untreated Control | Summary of Adverse Events | Subjects with at least one ocular serious adverse event related to study procedure for the study eye | 0 Participants |
| Untreated Control | Summary of Adverse Events | Subjects with at least one ocular adverse event related to surgical procedure for the study eye | 0 Participants |
| Untreated Control | Summary of Adverse Events | Subjects with at least one non-ocular adverse event | 44 Participants |
| Untreated Control | Summary of Adverse Events | Subjects with at least one non-ocular serious adverse event | 10 Participants |
| Untreated Control | Summary of Adverse Events | Subjects with at least one non-ocular adverse event related to surgical procedure | 0 Participants |
| Untreated Control | Summary of Adverse Events | Subjects with at least one ocular adverse event for the fellow eye | 14 Participants |
| Untreated Control | Summary of Adverse Events | Subjects with at least one ocular serious adverse event (SAE) for the study eye | 0 Participants |
| Untreated Control | Summary of Adverse Events | Subjects with at least one ocular adverse event related to study procedure for the study eye | 0 Participants |
| Untreated Control | Summary of Adverse Events | Subjects with at least one ocular adverse event for the study eye | 15 Participants |
Secondary
The Change From Baseline at Week 96 in Geographic Atrophy (GA)
GA area as measured by fundus autofluorescence (FAF)
Time frame: Baseline, Week 96
Population: Full Analysis Set - for participants with a valid measurement without a protocol deviation with impact.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| GT005 Medium Dose [5E10 vg] | The Change From Baseline at Week 96 in Geographic Atrophy (GA) | 4.414 mm2 | Standard Error 0.3109 |
| GT005 High Dose [2E11 vg] | The Change From Baseline at Week 96 in Geographic Atrophy (GA) | 4.607 mm2 | Standard Error 0.3167 |
| Untreated Control | The Change From Baseline at Week 96 in Geographic Atrophy (GA) | 3.769 mm2 | Standard Error 0.3286 |
Comparison: Week 9690% CI: [-0.103, 1.393]mixed model repeated measures
Comparison: Week 9690% CI: [0.081, 1.594]mixed model repeated measures