Dry Age-related Macular Degeneration
Conditions
Keywords
Geographic atrophy, Retinal disease, Eye disease, Retinal degeneration, Macular atrophy, Dry age-related macular degeneration
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, outcomes assessor-masked, multicentre, randomized study to assess 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 202 subjects were planned to be randomized to GT005 or the untreated control group. Subjects entered the study had genotyping and serum complement factor I(CFI) levels assessed. Assessments were either performed at a sponsor-approved laboratory during the EXPLORE screening period or provided through participation in a previous Gyroscope sponsored study. If subjects failed to meet the eligibility criteria for EXPLORE, they were classified as screen failures for this study and could be considered for entry into another Novartis/Gyroscope sponsored study. After providing the informed consent, subjects underwent ophthalmic and clinical assessments to determine eligibility for inclusion in the study. Upon confirmation of eligibility, subjects in part 1 were randomized to one of two groups: low dose \[2E10 vg\], or high dose \[2E11 vg\]. Within each group, subjects were allocated to GT005 or untreated control based on a 2:1 ratio. Once part 1 enrolment was completed, and the last active subject completed screening and either was screen-failed or randomized, then Part 2 could commence. In part 2, subjects were randomized to the low dose \[2E10\] group or untreated control based on a 2:1 ratio. The study eye was identified for all subjects. Subjects were stratified by GA lesion size on fundus autofluorescence (FAF) (≤10 mm2 or \>10 mm2) and presence of choroidal neovascularisation (CNV) in the fellow eye (Yes or No). 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. Once enrolment capping at 20% based on the 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. Of all subjects enrolled and randomized in the study, the presence of CNV in the fellow eye was capped at 25% per stratum. A permuted-block randomization 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, all imaging endpoint assessments and grading were performed at a Central Reading Centre (CRC), in a masked fashion. For part 1, the Sponsor, subject, investigators, and study personnel performing clinical assessments remained masked to dose received for those allocated to GT005. For part 2, the Sponsor, investigators, subjects, and study personnel performing clinical assessments were unmasked to dose received, since only the low dose was administered. Subjects randomized to GT005 underwent a single time subretinal administration of the study drug. Vitreous samples were collected during surgery. Following surgery, a prophylactic steroid regimen was prescribed. The study consisted 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 adverse events (AEs) at each visit and underwent functional visual and retinal imaging,anatomical assessments, and biological sampling as per the schedule of assessments. This study was conducted in compliance with Independent ethics committees (IECs) / Institutional review board (IRBs), informed consent regulations, the Declaration of Helsinki, International Council on Harmonisation (ICH) Good Clinical Practices (GCP) Guidelines, and the Food and Drug Administration (FDA) guidance. 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 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 / NCT05481827) study. In both Part 1 and Part 2, patients with geographic atrophy secondary to age-related macular degeneration were enrolled. In Part 1, patients with CFI rare variant genotype and low serum CFI level and in Part 2, patients were enrolled regardless of genotypes. Efficacy results were analyzed by arm and also by part. AE and disposition data were reported per arm, but the parts were combined, according to the analysis plan. Part 1 enrolled subjects with CFI rare variant; Part 2 enrolled subjects regardless of genotype. There were no subjects in the high dose arm in Part 2.
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
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 2, outcomes assessor-masked multicentre, randomised 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. 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 (except if the subject is monocular) 4. Have GA lesion(s) total size between or equal to 1.25mm2 to 17.5mm2 in the study eye 5. The GA lesion(s) 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, defined as either: 1. Non-exudative/sub-clinical fellow eye CNV identified at Screening, or 2. Known history of fellow eye CNV with either ≥2 years since diagnosis or with no active treatment required in 6 months prior to Screening 7. Have a BCVA of 24 letters (6/95 and 20/320 Snellen acuity equivalent) or better, using ETDRS charts, in the study eye 8. Part 1 Only: Subjects carrying a CFI rare variant genotype (minor allele frequency of ≤1%) previously associated with low serum CFI or subjects carrying an unreported CFI rare variant genotype that have tested to have a low serum CFI 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. A pregnancy test is not required for postmenopausal women (defined as being at least 12 consecutive months without menses) or those surgically sterilised (those having a bilateral tubal ligation/bilateral salpingectomy, bilateral tubal occlusive procedure, hysterectomy, or bilateral oophorectomy)
Exclusion criteria
1. Subjects who have a clinical diagnosis of Stargardt Disease or other retinal dystrophies, confirmed by the central reading centre 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 Screening (Visit 1). Yttrium aluminium garnet capsulotomy is permitted if performed \>10 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 in the study eye; uncontrolled IOP despite the use of two or more topical agents; a history of glaucoma-filtering or valve surgery is also excluded 8. Axial myopia of greater than -8 dioptres in the study eye 9. 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 10. Have a contraindication to specified protocol corticosteroid regimen 11. Have received any investigational and/or approved product(s) 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 in the study eye or systemically 12. Have received a gene or cell therapy at any time 13. Are unwilling to use two forms of contraception (one of which being a barrier method) for 90 days post-dosing, if relevant 14. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Change From Baseline to Week 48 in Geographic Atrophy (GA) - Part 1 | Baseline, Weeks 12, 24, 36, and 48 | The change from baseline to Week 48 in GA area as measured by fundus autofluorescence (FAF) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Change From Baseline in Geographic Atrophy (GA) at Week 72 and Week 96 - Part 1 | Baseline, Weeks 72 and 96 | The change from baseline to Week 48 in GA area as measured by fundus autofluorescence (FAF) |
| Summary of Adverse Events - Parts 1 and 2 Combined | Adverse events are reported from randomization up to end of study, for 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 Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | Adverse events are reported from randomization up to end of study, for 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 Adverse Events - Summary - Parts 1 and 2 Combined | Adverse events are reported from randomization up to end of study, for 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 Colour Fundus Photography (CFP) - Number of Participants With Increase in Fundus Autofluorescence (FAF) - Part 1 | Baseline, Weeks 5,12,24,36,48,72,96 | Change in GA morphology on multimodal imaging through Week 96. FAF images at Week 5 were introduced via a protocol amendment after most participants had already completed Week 5; therefore, only a minimal number of patients had FAF images taken at Week 5 for Part 1. |
| Change From Baseline to Week 48 in GA Morphology on Colour Fundus Photography (CFP) - Number of Participants With Increase in Fundus Autofluorescence - Part 2 | Baseline, Weeks 5,12,24,36,48 | Change in GA morphology on multimodal imaging through Week 48. For the untreated control group, there were no protocol-specified visits for Weeks 5 and 8. The untreated control participants were immediately discontinued from the study when the study was early terminated; therefore Week 36 and 48 data in part 2 were not applicable for these the untreated control group. |
| Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart - Part 1 | 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 - Part 1 | 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. |
| Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, and 48, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart - Part 2 | Baseline, Weeks 12, 24, 36, and 48 | 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. |
| Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Reading Performance, Measured as the Maximum Reading Speed (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart - Part 1 | Baseline, Weeks 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 and 48 in Reading Performance, Measured as the Maximum Reading Speed (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart - Part 2 | Baseline, Weeks 24, 36 and 48 | A higher count represents better visual functioning. The untreated control participants were immediately discontinued from the study when the study was early terminated; therefore Week 36 and 48 data in part 2 were not applicable for these the untreated control group. |
| Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index - Part 1 | 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 and 48 in Functional Reading Independence (FRI) Index - Part 2 | Baseline, Weeks 24, 36 and 48 | 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. The untreated control participants were immediately discontinued from the study when the study was early terminated; therefore Week 36 and 48 data in part 2 were not applicable for these the untreated control group. |
| Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score - Part 1 | 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. |
| Change From Baseline at Weeks 24, 36 and 48 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score - Part 2 | Baseline, Weeks 24, 36, and 48 | 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. The untreated control participants were immediately discontinued from the study when the study was early terminated; therefore Week 36 and 48 data in part 2 were not applicable for these the untreated control group. |
Countries
Australia, France, Germany, Netherlands, Poland, Spain, United Kingdom, United States
Participant flow
Recruitment details
This was a randomized, controlled study designed to evaluate the safety and efficacy of two doses of GT005 administered as a single subretinal injection in subjects with GA secondary to AMD. This was a study conducted in 3 treatment arms (GT005 low dose, GT005 high dose, and an untreated control group) and in 2 parts (Part 1 enrolled subjects with Complement factor I (CFI) rare variant; Part 2 enrolled subjects regardless of genotype (i.e., CFI-rare and CFI-non-rare variants));
Pre-assignment details
The parts were determined by genotype and not treatment. Because genotype may influence disease progression, these parts were considered in the analysis of the efficacy endpoints only, but not safety, and not demographics, as pre-specified in the SAP and protocol.
Participants by arm
| Arm | Count |
|---|---|
| GT005 Low Dose [2E10 vg] GT005 Low Dose \[2E10 vg\] | 52 |
| GT005 High Dose [2E11 vg] GT005 High Dose \[2E11 vg\] | 9 |
| Untreated Control Subjects allocated to the untreated control group did not receive any treatment. | 37 |
| Total | 98 |
Baseline characteristics
| Characteristic | Untreated Control | Total | GT005 Low Dose [2E10 vg] | GT005 High Dose [2E11 vg] |
|---|---|---|---|---|
| Age, Continuous | 75.2 years STANDARD_DEVIATION 7.07 | 75.8 years STANDARD_DEVIATION 7.41 | 76.8 years STANDARD_DEVIATION 7.33 | 72.7 years STANDARD_DEVIATION 8.96 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 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 | 2 Participants | 4 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 35 Participants | 93 Participants | 51 Participants | 7 Participants |
| Sex: Female, Male Female | 18 Participants | 57 Participants | 34 Participants | 5 Participants |
| Sex: Female, Male Male | 19 Participants | 41 Participants | 18 Participants | 4 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 | 3 / 52 | 0 / 9 | 2 / 37 | 5 / 98 |
| other Total, other adverse events | 19 / 52 | 9 / 9 | 16 / 37 | 44 / 98 |
| serious Total, serious adverse events | 5 / 52 | 2 / 9 | 4 / 37 | 11 / 98 |
Outcome results
Primary
The Change From Baseline to Week 48 in Geographic Atrophy (GA) - Part 1
The change from baseline to Week 48 in GA area as measured by fundus autofluorescence (FAF)
Time frame: Baseline, Weeks 12, 24, 36, and 48
Population: Full Analysis Set - for randomized participants with a valid measurement without a protocol deviation with impact.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| GT005 Low Dose [2E10 vg] | The Change From Baseline to Week 48 in Geographic Atrophy (GA) - Part 1 | Part 1 Week 36 (n=6,7,10) | 1.800 mm^2 | Standard Error 0.374 |
| GT005 Low Dose [2E10 vg] | The Change From Baseline to Week 48 in Geographic Atrophy (GA) - Part 1 | Part 1 Week 12 (n=9,8,12) | 0.773 mm^2 | Standard Error 0.2151 |
| GT005 Low Dose [2E10 vg] | The Change From Baseline to Week 48 in Geographic Atrophy (GA) - Part 1 | Part 1 Week 48 (n=5,8,10) | 2.120 mm^2 | Standard Error 0.3726 |
| GT005 Low Dose [2E10 vg] | The Change From Baseline to Week 48 in Geographic Atrophy (GA) - Part 1 | Part 1 Week 24 (n=9,7,9) | 1.338 mm^2 | Standard Error 0.2763 |
| GT005 High Dose [2E11 vg] | The Change From Baseline to Week 48 in Geographic Atrophy (GA) - Part 1 | Part 1 Week 36 (n=6,7,10) | 2.044 mm^2 | Standard Error 0.3669 |
| GT005 High Dose [2E11 vg] | The Change From Baseline to Week 48 in Geographic Atrophy (GA) - Part 1 | Part 1 Week 24 (n=9,7,9) | 1.519 mm^2 | Standard Error 0.2845 |
| GT005 High Dose [2E11 vg] | The Change From Baseline to Week 48 in Geographic Atrophy (GA) - Part 1 | Part 1 Week 48 (n=5,8,10) | 2.378 mm^2 | Standard Error 0.3414 |
| GT005 High Dose [2E11 vg] | The Change From Baseline to Week 48 in Geographic Atrophy (GA) - Part 1 | Part 1 Week 12 (n=9,8,12) | 0.764 mm^2 | Standard Error 0.2159 |
| Untreated Control | The Change From Baseline to Week 48 in Geographic Atrophy (GA) - Part 1 | Part 1 Week 48 (n=5,8,10) | 1.144 mm^2 | Standard Error 0.304 |
| Untreated Control | The Change From Baseline to Week 48 in Geographic Atrophy (GA) - Part 1 | Part 1 Week 12 (n=9,8,12) | 0.482 mm^2 | Standard Error 0.1848 |
| Untreated Control | The Change From Baseline to Week 48 in Geographic Atrophy (GA) - Part 1 | Part 1 Week 24 (n=9,7,9) | 0.680 mm^2 | Standard Error 0.25 |
| Untreated Control | The Change From Baseline to Week 48 in Geographic Atrophy (GA) - Part 1 | Part 1 Week 36 (n=6,7,10) | 1.132 mm^2 | Standard Error 0.3229 |
Comparison: Week 1290% CI: [-0.195, 0.777]mixed model repeated measures
Comparison: Week 1290% CI: [-0.206, 0.769]mixed model repeated measures
Comparison: Week 2490% CI: [0.017, 1.299]mixed model repeated measures
Comparison: Week 2490% CI: [0.189, 1.49]mixed model repeated measures
Comparison: Week 3690% CI: [-0.177, 1.512]mixed model repeated measures
Comparison: Week 3690% CI: [0.078, 1.746]mixed model repeated measures
Comparison: Week 4890% CI: [0.15, 1.803]mixed model repeated measures
Comparison: Week 4890% CI: [0.445, 2.022]mixed model repeated measures
Secondary
Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index - Part 1
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 randomized participants with a valid measurement without a protocol deviation with impact.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GT005 Low Dose [2E10 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index - Part 1 | Part 1 - Week 72 (n=5,7,10) | -3.8 Scores on a scale | Standard Deviation 4.6 |
| GT005 Low Dose [2E10 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index - Part 1 | Part 1 - Week 48 (n=6,7,10) | 0.5 Scores on a scale | Standard Deviation 2.43 |
| GT005 Low Dose [2E10 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index - Part 1 | Part 1 - Week 24 (n=9,8,10) | 0.7 Scores on a scale | Standard Deviation 3.57 |
| GT005 Low Dose [2E10 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index - Part 1 | Part 1 - Week 36 (n=8,5,10) | -1.0 Scores on a scale | Standard Deviation 4.24 |
| GT005 Low Dose [2E10 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index - Part 1 | Part 1 - Week 96 (n=6,6,7) | -2.7 Scores on a scale | Standard Deviation 5.79 |
| GT005 High Dose [2E11 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index - Part 1 | Part 1 - Week 48 (n=6,7,10) | -0.1 Scores on a scale | Standard Deviation 7.69 |
| GT005 High Dose [2E11 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index - Part 1 | Part 1 - Week 24 (n=9,8,10) | -1.3 Scores on a scale | Standard Deviation 2.55 |
| GT005 High Dose [2E11 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index - Part 1 | Part 1 - Week 36 (n=8,5,10) | 2.6 Scores on a scale | Standard Deviation 4.1 |
| GT005 High Dose [2E11 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index - Part 1 | Part 1 - Week 72 (n=5,7,10) | 0.4 Scores on a scale | Standard Deviation 3.41 |
| GT005 High Dose [2E11 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index - Part 1 | Part 1 - Week 96 (n=6,6,7) | -2.0 Scores on a scale | Standard Deviation 3.29 |
| Untreated Control | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index - Part 1 | Part 1 - Week 96 (n=6,6,7) | -0.7 Scores on a scale | Standard Deviation 5.53 |
| Untreated Control | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index - Part 1 | Part 1 - Week 72 (n=5,7,10) | -1.3 Scores on a scale | Standard Deviation 4.35 |
| Untreated Control | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index - Part 1 | Part 1 - Week 24 (n=9,8,10) | -0.3 Scores on a scale | Standard Deviation 4.06 |
| Untreated Control | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index - Part 1 | Part 1 - Week 48 (n=6,7,10) | -3.4 Scores on a scale | Standard Deviation 4.38 |
| Untreated Control | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index - Part 1 | Part 1 - Week 36 (n=8,5,10) | -0.6 Scores on a scale | Standard Deviation 4.72 |
Secondary
Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score - Part 1
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 randomized participants with a valid measurement without a protocol deviation with impact.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GT005 Low Dose [2E10 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score - Part 1 | Part 1 - Week 72 (n=5,8,10) | -8.698 Scores on a Scale | Standard Deviation 22.1289 |
| GT005 Low Dose [2E10 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score - Part 1 | Part 1 - Week 48 (n=6,8,10) | -6.439 Scores on a Scale | Standard Deviation 24.2128 |
| GT005 Low Dose [2E10 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score - Part 1 | Part 1 - Week 24 (n=9,9,10) | -2.312 Scores on a Scale | Standard Deviation 5.7079 |
| GT005 Low Dose [2E10 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score - Part 1 | Part 1 - Week 36 (n=8,6,10) | -4.400 Scores on a Scale | Standard Deviation 11.1307 |
| GT005 Low Dose [2E10 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score - Part 1 | Part 1 - Week 96 (n=6,7,7) | -10.352 Scores on a Scale | Standard Deviation 23.947 |
| 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 - Part 1 | Part 1 - Week 48 (n=6,8,10) | -6.810 Scores on a Scale | Standard Deviation 11.598 |
| 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 - Part 1 | Part 1 - Week 24 (n=9,9,10) | -3.755 Scores on a Scale | Standard Deviation 7.447 |
| 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 - Part 1 | Part 1 - Week 36 (n=8,6,10) | 1.960 Scores on a Scale | Standard Deviation 9.0113 |
| 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 - Part 1 | Part 1 - Week 72 (n=5,8,10) | -3.332 Scores on a Scale | Standard Deviation 8.147 |
| 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 - Part 1 | Part 1 - Week 96 (n=6,7,7) | 0.171 Scores on a Scale | Standard Deviation 11.3543 |
| Untreated Control | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score - Part 1 | Part 1 - Week 96 (n=6,7,7) | -10.700 Scores on a Scale | Standard Deviation 11.69 |
| Untreated Control | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score - Part 1 | Part 1 - Week 72 (n=5,8,10) | -3.826 Scores on a Scale | Standard Deviation 11.0029 |
| Untreated Control | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score - Part 1 | Part 1 - Week 24 (n=9,9,10) | -7.304 Scores on a Scale | Standard Deviation 12.5136 |
| Untreated Control | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score - Part 1 | Part 1 - Week 48 (n=6,8,10) | -4.091 Scores on a Scale | Standard Deviation 15.3598 |
| Untreated Control | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score - Part 1 | Part 1 - Week 36 (n=8,6,10) | -4.706 Scores on a Scale | Standard Deviation 11.8617 |
Secondary
Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Reading Performance, Measured as the Maximum Reading Speed (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart - Part 1
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 24, 36, 48, 72 and 96
Population: Full Analysis Set - for randomized participants with a valid measurement without a protocol deviation with impact.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GT005 Low Dose [2E10 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Reading Performance, Measured as the Maximum Reading Speed (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart - Part 1 | Part 1 - Week 72 (n=5,7,9) | -20.796 Words read per minute | Standard Deviation 42.2571 |
| GT005 Low Dose [2E10 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Reading Performance, Measured as the Maximum Reading Speed (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart - Part 1 | Part 1 - Week 48 (n=4,7,9) | 10.397 Words read per minute | Standard Deviation 11.8698 |
| GT005 Low Dose [2E10 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Reading Performance, Measured as the Maximum Reading Speed (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart - Part 1 | Part 1 - Week 24 (n=9,8,9) | 20.384 Words read per minute | Standard Deviation 74.7769 |
| GT005 Low Dose [2E10 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Reading Performance, Measured as the Maximum Reading Speed (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart - Part 1 | Part 1 - Week 36 (n=7,7,8) | -15.048 Words read per minute | Standard Deviation 33.0479 |
| GT005 Low Dose [2E10 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Reading Performance, Measured as the Maximum Reading Speed (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart - Part 1 | Part 1 - Week 96 (n=6,5,5) | 10.802 Words read per minute | Standard Deviation 32.1161 |
| GT005 High Dose [2E11 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Reading Performance, Measured as the Maximum Reading Speed (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart - Part 1 | Part 1 - Week 48 (n=4,7,9) | -36.285 Words read per minute | Standard Deviation 40.0938 |
| GT005 High Dose [2E11 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Reading Performance, Measured as the Maximum Reading Speed (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart - Part 1 | Part 1 - Week 24 (n=9,8,9) | -36.154 Words read per minute | Standard Deviation 40.3322 |
| GT005 High Dose [2E11 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Reading Performance, Measured as the Maximum Reading Speed (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart - Part 1 | Part 1 - Week 36 (n=7,7,8) | -34.653 Words read per minute | Standard Deviation 27.2693 |
| GT005 High Dose [2E11 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Reading Performance, Measured as the Maximum Reading Speed (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart - Part 1 | Part 1 - Week 72 (n=5,7,9) | -44.913 Words read per minute | Standard Deviation 46.7594 |
| GT005 High Dose [2E11 vg] | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Reading Performance, Measured as the Maximum Reading Speed (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart - Part 1 | Part 1 - Week 96 (n=6,5,5) | -32.266 Words read per minute | Standard Deviation 36.9172 |
| Untreated Control | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Reading Performance, Measured as the Maximum Reading Speed (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart - Part 1 | Part 1 - Week 96 (n=6,5,5) | -21.602 Words read per minute | Standard Deviation 26.0643 |
| Untreated Control | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Reading Performance, Measured as the Maximum Reading Speed (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart - Part 1 | Part 1 - Week 72 (n=5,7,9) | -15.429 Words read per minute | Standard Deviation 30.1012 |
| Untreated Control | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Reading Performance, Measured as the Maximum Reading Speed (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart - Part 1 | Part 1 - Week 24 (n=9,8,9) | -7.837 Words read per minute | Standard Deviation 21.8918 |
| Untreated Control | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Reading Performance, Measured as the Maximum Reading Speed (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart - Part 1 | Part 1 - Week 48 (n=4,7,9) | -6.837 Words read per minute | Standard Deviation 31.6162 |
| Untreated Control | Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Reading Performance, Measured as the Maximum Reading Speed (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart - Part 1 | Part 1 - Week 36 (n=7,7,8) | -15.245 Words read per minute | Standard Deviation 22.0983 |
Secondary
Change From Baseline at Weeks 24, 36 and 48 in Functional Reading Independence (FRI) Index - Part 2
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. The untreated control participants were immediately discontinued from the study when the study was early terminated; therefore Week 36 and 48 data in part 2 were not applicable for these the untreated control group.
Time frame: Baseline, Weeks 24, 36 and 48
Population: Full Analysis Set - for randomized participants with a valid measurement without a protocol deviation with impact.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GT005 Low Dose [2E10 vg] | Change From Baseline at Weeks 24, 36 and 48 in Functional Reading Independence (FRI) Index - Part 2 | Part 2 - Week 24 (n=17,0,9) | -0.4 Scores on a scale | Standard Deviation 2.83 |
| GT005 Low Dose [2E10 vg] | Change From Baseline at Weeks 24, 36 and 48 in Functional Reading Independence (FRI) Index - Part 2 | Part 2 - Week 36 (n=14,0,0) | -1.7 Scores on a scale | Standard Deviation 3.83 |
| GT005 Low Dose [2E10 vg] | Change From Baseline at Weeks 24, 36 and 48 in Functional Reading Independence (FRI) Index - Part 2 | Part 2 - Week 48 (n=5,0,0) | 0.4 Scores on a scale | Standard Deviation 5.13 |
| Untreated Control | Change From Baseline at Weeks 24, 36 and 48 in Functional Reading Independence (FRI) Index - Part 2 | Part 2 - Week 24 (n=17,0,9) | 0.4 Scores on a scale | Standard Deviation 6.86 |
Secondary
Change From Baseline at Weeks 24, 36 and 48 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score - Part 2
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. The untreated control participants were immediately discontinued from the study when the study was early terminated; therefore Week 36 and 48 data in part 2 were not applicable for these the untreated control group.
Time frame: Baseline, Weeks 24, 36, and 48
Population: Full Analysis Set - for randomized participants with a valid measurement without a protocol deviation with impact.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GT005 Low Dose [2E10 vg] | Change From Baseline at Weeks 24, 36 and 48 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score - Part 2 | Part 2 - Week 24 (n=17,0,8) | -4.034 Scores on a Scale | Standard Deviation 6.8881 |
| GT005 Low Dose [2E10 vg] | Change From Baseline at Weeks 24, 36 and 48 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score - Part 2 | Part 2 - Week 36 (n=14,0,0) | -2.733 Scores on a Scale | Standard Deviation 7.9219 |
| GT005 Low Dose [2E10 vg] | Change From Baseline at Weeks 24, 36 and 48 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score - Part 2 | Part 2 - Week 48 (n=5,0,0) | -0.530 Scores on a Scale | Standard Deviation 6.9722 |
| Untreated Control | Change From Baseline at Weeks 24, 36 and 48 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score - Part 2 | Part 2 - Week 24 (n=17,0,8) | -3.070 Scores on a Scale | Standard Deviation 7.4251 |
Secondary
Change From Baseline at Weeks 24, 36 and 48 in Reading Performance, Measured as the Maximum Reading Speed (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart - Part 2
A higher count represents better visual functioning. The untreated control participants were immediately discontinued from the study when the study was early terminated; therefore Week 36 and 48 data in part 2 were not applicable for these the untreated control group.
Time frame: Baseline, Weeks 24, 36 and 48
Population: Full Analysis Set - for randomized participants with a valid measurement without a protocol deviation with impact.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GT005 Low Dose [2E10 vg] | Change From Baseline at Weeks 24, 36 and 48 in Reading Performance, Measured as the Maximum Reading Speed (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart - Part 2 | Part 2 - Week 24 (n=16,0,10) | 15.581 Words read per minute | Standard Deviation 78.2848 |
| GT005 Low Dose [2E10 vg] | Change From Baseline at Weeks 24, 36 and 48 in Reading Performance, Measured as the Maximum Reading Speed (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart - Part 2 | Part 2 - Week 36 (n=14,0,0) | 9.812 Words read per minute | Standard Deviation 94.4255 |
| GT005 Low Dose [2E10 vg] | Change From Baseline at Weeks 24, 36 and 48 in Reading Performance, Measured as the Maximum Reading Speed (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart - Part 2 | Part 2 - Week 48 (n=5,0,0) | -28.111 Words read per minute | Standard Deviation 38.6209 |
| Untreated Control | Change From Baseline at Weeks 24, 36 and 48 in Reading Performance, Measured as the Maximum Reading Speed (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart - Part 2 | Part 2 - Week 24 (n=16,0,10) | -30.707 Words read per minute | Standard Deviation 27.3225 |
Secondary
Change From Baseline to Week 48 in GA Morphology on Colour Fundus Photography (CFP) - Number of Participants With Increase in Fundus Autofluorescence - Part 2
Change in GA morphology on multimodal imaging through Week 48. For the untreated control group, there were no protocol-specified visits for Weeks 5 and 8. The untreated control participants were immediately discontinued from the study when the study was early terminated; therefore Week 36 and 48 data in part 2 were not applicable for these the untreated control group.
Time frame: Baseline, Weeks 5,12,24,36,48
Population: Full Analysis Set - for randomized participants with a valid measurement without a protocol deviation with impact.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GT005 Low Dose [2E10 vg] | Change From Baseline to Week 48 in GA Morphology on Colour Fundus Photography (CFP) - Number of Participants With Increase in Fundus Autofluorescence - Part 2 | Part 2 Week 24 (n=17,0,11) | 16 Participants |
| GT005 Low Dose [2E10 vg] | Change From Baseline to Week 48 in GA Morphology on Colour Fundus Photography (CFP) - Number of Participants With Increase in Fundus Autofluorescence - Part 2 | Part 2 Week 12 (n=17,0,20) | 17 Participants |
| GT005 Low Dose [2E10 vg] | Change From Baseline to Week 48 in GA Morphology on Colour Fundus Photography (CFP) - Number of Participants With Increase in Fundus Autofluorescence - Part 2 | Part 2 Week 36 (n=14,0,0) | 13 Participants |
| GT005 Low Dose [2E10 vg] | Change From Baseline to Week 48 in GA Morphology on Colour Fundus Photography (CFP) - Number of Participants With Increase in Fundus Autofluorescence - Part 2 | Part 2 Week 48 (n=5,0,0) | 5 Participants |
| GT005 Low Dose [2E10 vg] | Change From Baseline to Week 48 in GA Morphology on Colour Fundus Photography (CFP) - Number of Participants With Increase in Fundus Autofluorescence - Part 2 | Part 2 Week 5 (n= 16,0, 0) | 16 Participants |
| Untreated Control | Change From Baseline to Week 48 in GA Morphology on Colour Fundus Photography (CFP) - Number of Participants With Increase in Fundus Autofluorescence - Part 2 | Part 2 Week 12 (n=17,0,20) | 20 Participants |
| Untreated Control | Change From Baseline to Week 48 in GA Morphology on Colour Fundus Photography (CFP) - Number of Participants With Increase in Fundus Autofluorescence - Part 2 | Part 2 Week 24 (n=17,0,11) | 11 Participants |
Secondary
Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart - Part 1
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 randomized participants with a valid measurement without a protocol deviation with impact.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| GT005 Low Dose [2E10 vg] | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart - Part 1 | Part 1 - Week 1 (n=9,9,0) | -4.7 Letters read | Standard Error 4.04 |
| GT005 Low Dose [2E10 vg] | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart - Part 1 | Part 1 - Week 5 (n=8,9,0) | -1.7 Letters read | Standard Error 4.08 |
| GT005 Low Dose [2E10 vg] | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart - Part 1 | Part 1 - Week 8 (n=9,9,0) | -1.6 Letters read | Standard Error 4.03 |
| GT005 Low Dose [2E10 vg] | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart - Part 1 | Part 1 - Week 12 (N=9,9,12) | -2.3 Letters read | Standard Error 4.03 |
| GT005 Low Dose [2E10 vg] | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart - Part 1 | Part 1 - Week 24 (n=9,9,10) | -5.6 Letters read | Standard Error 4.03 |
| GT005 Low Dose [2E10 vg] | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart - Part 1 | Part 1 - Week 36 (n=8,8,10) | -10.0 Letters read | Standard Error 4.1 |
| GT005 Low Dose [2E10 vg] | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart - Part 1 | Part 1 - Week 48 (n=5,8,10) | -8.6 Letters read | Standard Error 4.52 |
| GT005 Low Dose [2E10 vg] | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart - Part 1 | Part 1 - Week 72 (n=5,8,10) | -6.3 Letters read | Standard Error 4.56 |
| GT005 Low Dose [2E10 vg] | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart - Part 1 | Part 1 - Week 96 (n=6,8,7) | -6.5 Letters read | Standard Error 4.5 |
| 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 - Part 1 | Part 1 - Week 72 (n=5,8,10) | -9.6 Letters read | Standard Error 4.34 |
| 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 - Part 1 | Part 1 - Week 24 (n=9,9,10) | -12.0 Letters read | Standard Error 4.18 |
| 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 - Part 1 | Part 1 - Week 1 (n=9,9,0) | -5.2 Letters read | Standard Error 4.27 |
| 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 - Part 1 | Part 1 - Week 48 (n=5,8,10) | -13.3 Letters read | Standard Error 4.32 |
| 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 - Part 1 | Part 1 - Week 5 (n=8,9,0) | -7.6 Letters read | Standard Error 4.26 |
| 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 - Part 1 | Part 1 - Week 8 (n=9,9,0) | -4.5 Letters read | Standard Error 4.23 |
| 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 - Part 1 | Part 1 - Week 96 (n=6,8,7) | -11.0 Letters read | Standard Error 4.33 |
| 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 - Part 1 | Part 1 - Week 12 (N=9,9,12) | -7.5 Letters read | Standard Error 4.18 |
| 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 - Part 1 | Part 1 - Week 36 (n=8,8,10) | -12.9 Letters read | Standard Error 4.28 |
| Untreated Control | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart - Part 1 | Part 1 - Week 24 (n=9,9,10) | -0.4 Letters read | Standard Error 3.87 |
| Untreated Control | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart - Part 1 | Part 1 - Week 72 (n=5,8,10) | -8.9 Letters read | Standard Error 3.94 |
| Untreated Control | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart - Part 1 | Part 1 - Week 48 (n=5,8,10) | -5.7 Letters read | Standard Error 3.91 |
| Untreated Control | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart - Part 1 | Part 1 - Week 36 (n=8,8,10) | -1.0 Letters read | Standard Error 3.89 |
| Untreated Control | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart - Part 1 | Part 1 - Week 96 (n=6,8,7) | -7.9 Letters read | Standard Error 4.3 |
| Untreated Control | Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart - Part 1 | Part 1 - Week 12 (N=9,9,12) | -1.2 Letters read | Standard Error 3.81 |
Comparison: Week 2490% CI: [-21.7, -1.6]mixed model repeated measures
Comparison: Week 1290% CI: [-10.3, 8.1]mixed model repeated measures
Comparison: Week 1290% CI: [-16.3, 3.7]mixed model repeated measures
Comparison: Week 2490% CI: [-14.5, 4.1]mixed model repeated measures
Comparison: Week 3690% CI: [-18.4, 0.5]mixed model repeated measures
Comparison: Week 3690% CI: [-22.1, -1.7]mixed model repeated measures
Comparison: Week 4890% CI: [-12.7, 6.9]mixed model repeated measures
Comparison: Week 4890% CI: [-17.9, 2.7]mixed model repeated measures
Comparison: Week 7290% CI: [-7.4, 12.5]mixed model repeated measures
Comparison: Week 7290% CI: [-11.1, 9.6]mixed model repeated measures
Comparison: Week 9690% CI: [-8.7, 11.5]mixed model repeated measures
Comparison: Week 9690% CI: [-13.8, 7.8]mixed model repeated measures
Secondary
Change in GA Morphology From Baseline to Week 96 on Colour Fundus Photography (CFP) - Number of Participants With Increase in Fundus Autofluorescence (FAF) - Part 1
Change in GA morphology on multimodal imaging through Week 96. FAF images at Week 5 were introduced via a protocol amendment after most participants had already completed Week 5; therefore, only a minimal number of patients had FAF images taken at Week 5 for Part 1.
Time frame: Baseline, Weeks 5,12,24,36,48,72,96
Population: Full Analysis Set - for randomized participants with a valid measurement without a protocol deviation with impact.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GT005 Low Dose [2E10 vg] | Change in GA Morphology From Baseline to Week 96 on Colour Fundus Photography (CFP) - Number of Participants With Increase in Fundus Autofluorescence (FAF) - Part 1 | Part 1 Week 72 (n=5,8,9) | 5 Participants |
| GT005 Low Dose [2E10 vg] | Change in GA Morphology From Baseline to Week 96 on Colour Fundus Photography (CFP) - Number of Participants With Increase in Fundus Autofluorescence (FAF) - Part 1 | Part 1 Week 96 (n=6,8,7) | 6 Participants |
| GT005 Low Dose [2E10 vg] | Change in GA Morphology From Baseline to Week 96 on Colour Fundus Photography (CFP) - Number of Participants With Increase in Fundus Autofluorescence (FAF) - Part 1 | Part 1 Week 36 (n=6,7,10) | 5 Participants |
| GT005 Low Dose [2E10 vg] | Change in GA Morphology From Baseline to Week 96 on Colour Fundus Photography (CFP) - Number of Participants With Increase in Fundus Autofluorescence (FAF) - Part 1 | Part 1 Week 12 (n=9,8,12) | 8 Participants |
| GT005 Low Dose [2E10 vg] | Change in GA Morphology From Baseline to Week 96 on Colour Fundus Photography (CFP) - Number of Participants With Increase in Fundus Autofluorescence (FAF) - Part 1 | Part 1 Week 48 (n=5,8,10) | 5 Participants |
| GT005 Low Dose [2E10 vg] | Change in GA Morphology From Baseline to Week 96 on Colour Fundus Photography (CFP) - Number of Participants With Increase in Fundus Autofluorescence (FAF) - Part 1 | Part 1 Week 24 (n=9,7,10) | 8 Participants |
| GT005 High Dose [2E11 vg] | Change in GA Morphology From Baseline to Week 96 on Colour Fundus Photography (CFP) - Number of Participants With Increase in Fundus Autofluorescence (FAF) - Part 1 | Part 1 Week 12 (n=9,8,12) | 8 Participants |
| GT005 High Dose [2E11 vg] | Change in GA Morphology From Baseline to Week 96 on Colour Fundus Photography (CFP) - Number of Participants With Increase in Fundus Autofluorescence (FAF) - Part 1 | Part 1 Week 48 (n=5,8,10) | 8 Participants |
| GT005 High Dose [2E11 vg] | Change in GA Morphology From Baseline to Week 96 on Colour Fundus Photography (CFP) - Number of Participants With Increase in Fundus Autofluorescence (FAF) - Part 1 | Part 1 Week 72 (n=5,8,9) | 8 Participants |
| GT005 High Dose [2E11 vg] | Change in GA Morphology From Baseline to Week 96 on Colour Fundus Photography (CFP) - Number of Participants With Increase in Fundus Autofluorescence (FAF) - Part 1 | Part 1 Week 24 (n=9,7,10) | 7 Participants |
| GT005 High Dose [2E11 vg] | Change in GA Morphology From Baseline to Week 96 on Colour Fundus Photography (CFP) - Number of Participants With Increase in Fundus Autofluorescence (FAF) - Part 1 | Part 1 Week 36 (n=6,7,10) | 7 Participants |
| GT005 High Dose [2E11 vg] | Change in GA Morphology From Baseline to Week 96 on Colour Fundus Photography (CFP) - Number of Participants With Increase in Fundus Autofluorescence (FAF) - Part 1 | Part 1 Week 96 (n=6,8,7) | 8 Participants |
| GT005 High Dose [2E11 vg] | Change in GA Morphology From Baseline to Week 96 on Colour Fundus Photography (CFP) - Number of Participants With Increase in Fundus Autofluorescence (FAF) - Part 1 | Part 1 Week 5 (n= 0,2,0) | 2 Participants |
| Untreated Control | Change in GA Morphology From Baseline to Week 96 on Colour Fundus Photography (CFP) - Number of Participants With Increase in Fundus Autofluorescence (FAF) - Part 1 | Part 1 Week 96 (n=6,8,7) | 7 Participants |
| Untreated Control | Change in GA Morphology From Baseline to Week 96 on Colour Fundus Photography (CFP) - Number of Participants With Increase in Fundus Autofluorescence (FAF) - Part 1 | Part 1 Week 12 (n=9,8,12) | 11 Participants |
| Untreated Control | Change in GA Morphology From Baseline to Week 96 on Colour Fundus Photography (CFP) - Number of Participants With Increase in Fundus Autofluorescence (FAF) - Part 1 | Part 1 Week 24 (n=9,7,10) | 10 Participants |
| Untreated Control | Change in GA Morphology From Baseline to Week 96 on Colour Fundus Photography (CFP) - Number of Participants With Increase in Fundus Autofluorescence (FAF) - Part 1 | Part 1 Week 36 (n=6,7,10) | 10 Participants |
| Untreated Control | Change in GA Morphology From Baseline to Week 96 on Colour Fundus Photography (CFP) - Number of Participants With Increase in Fundus Autofluorescence (FAF) - Part 1 | Part 1 Week 48 (n=5,8,10) | 10 Participants |
| Untreated Control | Change in GA Morphology From Baseline to Week 96 on Colour Fundus Photography (CFP) - Number of Participants With Increase in Fundus Autofluorescence (FAF) - Part 1 | Part 1 Week 72 (n=5,8,9) | 9 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 - Part 1
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 randomized participants with a valid measurement without a protocol deviation with impact.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GT005 Low Dose [2E10 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 - Part 1 | Part 1 - Week 12 (N=9,9,12) | 2.0 Letters read | Standard Deviation 9.06 |
| GT005 Low Dose [2E10 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 - Part 1 | Part 1 - Week 24 (n=9,9,10) | 2.1 Letters read | Standard Deviation 8.4 |
| GT005 Low Dose [2E10 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 - Part 1 | Part 1 - Week 36 (n=8,8,10) | 2.3 Letters read | Standard Deviation 15.65 |
| GT005 Low Dose [2E10 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 - Part 1 | Part 1 - Week 48 (n=5,8,10) | 3.0 Letters read | Standard Deviation 6.96 |
| GT005 Low Dose [2E10 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 - Part 1 | Part 1 - Week 72 (n=5,8,10) | 4.4 Letters read | Standard Deviation 7.57 |
| GT005 Low Dose [2E10 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 - Part 1 | Part 1 - Week 96 (n=6,8,6) | 5.2 Letters read | Standard Deviation 8.47 |
| 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 - Part 1 | Part 1 - Week 96 (n=6,8,6) | 1.5 Letters read | Standard Deviation 29.17 |
| 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 - Part 1 | Part 1 - Week 12 (N=9,9,12) | 2.4 Letters read | Standard Deviation 22.49 |
| 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 - Part 1 | Part 1 - Week 48 (n=5,8,10) | 1.8 Letters read | Standard Deviation 26.25 |
| 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 - Part 1 | Part 1 - Week 72 (n=5,8,10) | 3.1 Letters read | Standard Deviation 32.24 |
| 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 - Part 1 | Part 1 - Week 24 (n=9,9,10) | 2.9 Letters read | Standard Deviation 24.81 |
| 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 - Part 1 | Part 1 - Week 36 (n=8,8,10) | -7.5 Letters read | Standard Deviation 19.41 |
| 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 - Part 1 | Part 1 - Week 24 (n=9,9,10) | -2.9 Letters read | Standard Deviation 7.68 |
| 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 - Part 1 | Part 1 - Week 36 (n=8,8,10) | -4.0 Letters read | Standard Deviation 12.51 |
| 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 - Part 1 | Part 1 - Week 96 (n=6,8,6) | -10.5 Letters read | Standard Deviation 27.41 |
| 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 - Part 1 | Part 1 - Week 48 (n=5,8,10) | -6.2 Letters read | Standard Deviation 19.99 |
| 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 - Part 1 | Part 1 - Week 12 (N=9,9,12) | -2.0 Letters read | Standard Deviation 7.21 |
| 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 - Part 1 | Part 1 - Week 72 (n=5,8,10) | -6.6 Letters read | Standard Deviation 21.15 |
Secondary
Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, and 48, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart - Part 2
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, and 48
Population: Full Analysis Set - for randomized participants with a valid measurement without a protocol deviation with impact. The untreated control participants were immediately discontinued from the study when the study was early terminated; therefore Week 36 and 48 data in part 2 were not applicable for these the untreated control group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GT005 Low Dose [2E10 vg] | Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, and 48, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart - Part 2 | Part 2 - Week 12 (N=18,0,20) | 0.7 Letters read | Standard Deviation 10.83 |
| GT005 Low Dose [2E10 vg] | Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, and 48, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart - Part 2 | Part 2 - Week 24 (n=17,0,10) | 2.6 Letters read | Standard Deviation 9.98 |
| GT005 Low Dose [2E10 vg] | Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, and 48, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart - Part 2 | Part 2 - Week 36 (n=14,0,0) | 4.6 Letters read | Standard Deviation 11.77 |
| GT005 Low Dose [2E10 vg] | Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, and 48, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart - Part 2 | Part 2 - Week 48 (n=5,0,0) | -2.8 Letters read | Standard Deviation 4.32 |
| Untreated Control | Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, and 48, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart - Part 2 | Part 2 - Week 12 (N=18,0,20) | -1.4 Letters read | Standard Deviation 11.76 |
| Untreated Control | Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, and 48, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart - Part 2 | Part 2 - Week 24 (n=17,0,10) | -1.6 Letters read | Standard Deviation 20.13 |
Secondary
Non-ocular Adverse Events - Summary - Parts 1 and 2 Combined
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 up to end of study, for a maximum timeframe of approximately 96 weeks.
Population: Full Analysis Set - all randomized participants. Part 1 enrolled subjects with Complement factor I (CFI) rare variant; Part 2 enrolled subjects regardless of genotype (i.e., CFI-rare and CFI-non-rare variants) . Part 1 and Part 2 are not defined in the protocol as distinct arms. Since there were no safety concerns, it was determined that there was no scientific value in reporting safety results by part / genotype, but by treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GT005 Low Dose [2E10 vg] | Non-ocular Adverse Events - Summary - Parts 1 and 2 Combined | 13 Participants |
| GT005 High Dose [2E11 vg] | Non-ocular Adverse Events - Summary - Parts 1 and 2 Combined | 8 Participants |
| Untreated Control | Non-ocular Adverse Events - Summary - Parts 1 and 2 Combined | 14 Participants |
Secondary
Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined
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 up to end of study, for a maximum timeframe of approximately 96 weeks.
Population: Full Analysis Set - all randomized participants. Part 1 enrolled subjects with Complement factor I (CFI) rare variant; Part 2 enrolled subjects regardless of genotype (i.e., CFI-rare and CFI-non-rare variants) . Part 1 and Part 2 are not defined in the protocol as distinct arms. Since there were no safety concerns, it was determined that there was no scientific value in reporting safety results by part / genotype, but by treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Retinal depigmentation | 1 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Eye pruritus | 0 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Retinal pigmentation | 3 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Punctate keratitis | 1 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Hypotony maculopathy | 0 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | Subjects with at least one event | 18 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Posterior capsule opacification | 0 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Iridocyclitis | 0 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Eye pain | 1 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Photopsia | 1 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Iritis | 1 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | Eye disorders | 15 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Photophobia | 0 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Keratitis | 1 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Procedural pain | 1 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Open angle glaucoma | 0 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Lacrimation increased | 0 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Retinal haemorrhage | 2 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Ocular hypertension | 1 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Macular hole | 1 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Intraocular pressure increased | 4 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Metamorphopsia | 1 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Meibomian gland dysfunction | 1 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Post procedural discomfort | 2 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Anterior chamber cell | 1 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Conjunctival haemorrhage | 6 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | Injury, poisoning and procedural complications | 4 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Blepharitis | 2 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Telangiectasia | 1 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Vitreous haemorrhage | 1 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Conjunctivitis allergic | 1 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | Investigations | 4 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Vitreous floaters | 1 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Anterior chamber flare | 0 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Cataract | 3 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Visual snow syndrome | 1 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Choroidal detachment | 0 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | Skin and subcutaneous tissue disorders | 1 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Visual impairment | 1 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Conjunctival hyperaemia | 1 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Suture related complication | 1 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Visual acuity reduced | 1 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Dry eye | 1 Participants |
| GT005 Low Dose [2E10 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Cataract nuclear | 2 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Procedural pain | 1 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | Subjects with at least one event | 9 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | Eye disorders | 9 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Retinal pigmentation | 6 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Conjunctival haemorrhage | 1 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Cataract | 2 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Cataract nuclear | 1 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Eye pain | 2 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Retinal haemorrhage | 1 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Anterior chamber cell | 1 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Blepharitis | 0 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Conjunctivitis allergic | 1 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Anterior chamber flare | 1 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Choroidal detachment | 1 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Conjunctival hyperaemia | 0 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Dry eye | 0 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Eye pruritus | 0 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Hypotony maculopathy | 1 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Iridocyclitis | 1 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Iritis | 0 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Keratitis | 0 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Lacrimation increased | 1 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Macular hole | 0 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Meibomian gland dysfunction | 0 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Metamorphopsia | 0 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Ocular hypertension | 0 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Open angle glaucoma | 1 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Photophobia | 1 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Photopsia | 0 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Posterior capsule opacification | 0 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Punctate keratitis | 0 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Retinal depigmentation | 0 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Visual acuity reduced | 0 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Visual impairment | 0 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Visual snow syndrome | 0 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Vitreous floaters | 0 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Vitreous haemorrhage | 0 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | Injury, poisoning and procedural complications | 1 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Post procedural discomfort | 0 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Suture related complication | 1 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | Investigations | 3 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Intraocular pressure increased | 3 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | Skin and subcutaneous tissue disorders | 0 Participants |
| GT005 High Dose [2E11 vg] | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Telangiectasia | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Telangiectasia | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Punctate keratitis | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Dry eye | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Suture related complication | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Retinal depigmentation | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Conjunctival hyperaemia | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Conjunctival haemorrhage | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Visual acuity reduced | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Choroidal detachment | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | Skin and subcutaneous tissue disorders | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Visual impairment | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Anterior chamber flare | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | Investigations | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Visual snow syndrome | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Conjunctivitis allergic | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Retinal pigmentation | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Vitreous floaters | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Blepharitis | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | Subjects with at least one event | 2 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Vitreous haemorrhage | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Anterior chamber cell | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Intraocular pressure increased | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | Injury, poisoning and procedural complications | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Retinal haemorrhage | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Meibomian gland dysfunction | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Macular hole | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | Eye disorders | 2 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Metamorphopsia | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Lacrimation increased | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Post procedural discomfort | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Ocular hypertension | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Keratitis | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Eye pain | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Open angle glaucoma | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Iritis | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Cataract nuclear | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Photophobia | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Iridocyclitis | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Procedural pain | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Photopsia | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Hypotony maculopathy | 0 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Cataract | 1 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Posterior capsule opacification | 1 Participants |
| Untreated Control | Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined | -Eye pruritus | 1 Participants |
Secondary
Summary of Adverse Events - Parts 1 and 2 Combined
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 up to end of study, for a maximum timeframe of approximately 96 weeks.
Population: Full Analysis Set - all randomized participants. Part 1 enrolled subjects with Complement factor I (CFI) rare variant; Part 2 enrolled subjects regardless of genotype (i.e., CFI-rare and CFI-non-rare variants) . Part 1 and Part 2 are not defined in the protocol as distinct arms. Since there were no safety concerns, it was determined that there was no scientific value in reporting safety results by part / genotype, but by treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GT005 Low Dose [2E10 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one ocular adverse event related to study treatment for the study eye | 3 Participants |
| GT005 Low Dose [2E10 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one ocular serious adverse event related to study treatment for the study eye | 0 Participants |
| GT005 Low Dose [2E10 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one ocular adverse event leading to study discontinuation for the study eye | 0 Participants |
| GT005 Low Dose [2E10 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Deaths | 3 Participants |
| GT005 Low Dose [2E10 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one ocular adverse event for the study eye | 18 Participants |
| GT005 Low Dose [2E10 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one non-ocular adverse event leading to study discontinuation | 3 Participants |
| GT005 Low Dose [2E10 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one non-ocular serious adverse event related to study procedure | 0 Participants |
| GT005 Low Dose [2E10 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one non-ocular serious adverse event | 5 Participants |
| GT005 Low Dose [2E10 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one ocular adverse event of special interest for the study eye | 4 Participants |
| GT005 Low Dose [2E10 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one non-ocular adverse event related to study treatment | 0 Participants |
| GT005 Low Dose [2E10 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one ocular serious adverse event for the fellow eye | 0 Participants |
| GT005 Low Dose [2E10 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one ocular adverse event of special interest for the fellow eye | 0 Participants |
| GT005 Low Dose [2E10 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one non-ocular serious adverse event leading to study discontinuation | 3 Participants |
| GT005 Low Dose [2E10 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one ocular serious adverse event (SAE) for the study eye | 1 Participants |
| GT005 Low Dose [2E10 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one ocular serious adverse event related to study procedure for the study eye | 0 Participants |
| GT005 Low Dose [2E10 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one ocular adverse event related to surgical procedure for the study eye | 12 Participants |
| GT005 Low Dose [2E10 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one non-ocular adverse event | 13 Participants |
| GT005 Low Dose [2E10 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one non-ocular serious adverse event related to surgical procedure | 0 Participants |
| GT005 Low Dose [2E10 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one non-ocular adverse event related to surgical procedure | 0 Participants |
| GT005 Low Dose [2E10 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one ocular adverse event for the fellow eye | 6 Participants |
| GT005 Low Dose [2E10 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least 1 ocular SAE related to surgical procedure - study eye | 0 Participants |
| GT005 Low Dose [2E10 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one ocular adverse event related to study procedure for the study eye | 1 Participants |
| GT005 Low Dose [2E10 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least 1 ocular SAE event leading to study discontinuation- study eye | 0 Participants |
| GT005 Low Dose [2E10 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one non-ocular serious adverse event related to study treatment | 0 Participants |
| GT005 Low Dose [2E10 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one non-ocular adverse event related to study procedure | 1 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one non-ocular serious adverse event | 2 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one ocular adverse event for the study eye | 9 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one ocular adverse event for the fellow eye | 3 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one non-ocular adverse event | 8 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one ocular adverse event related to study treatment for the study eye | 4 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one non-ocular adverse event related to study treatment | 0 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one ocular adverse event related to surgical procedure for the study eye | 7 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one non-ocular adverse event related to surgical procedure | 0 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one ocular adverse event related to study procedure for the study eye | 1 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one non-ocular adverse event related to study procedure | 0 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | 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 - Parts 1 and 2 Combined | Subjects with at least one non-ocular adverse event leading to study discontinuation | 0 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one ocular adverse event of special interest for the study eye | 7 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one ocular adverse event of special interest for the fellow eye | 0 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one ocular serious adverse event (SAE) for the study eye | 0 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one ocular serious adverse event for the fellow eye | 0 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | 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 - Parts 1 and 2 Combined | 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 - Parts 1 and 2 Combined | Subjects with at least 1 ocular SAE related to surgical procedure - study eye | 0 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | 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 - Parts 1 and 2 Combined | Subjects with at least one ocular serious adverse event related to study procedure for the study eye | 0 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | 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 - Parts 1 and 2 Combined | Subjects with at least 1 ocular SAE event leading to study discontinuation- study eye | 0 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one non-ocular serious adverse event leading to study discontinuation | 0 Participants |
| GT005 High Dose [2E11 vg] | Summary of Adverse Events - Parts 1 and 2 Combined | Deaths | 0 Participants |
| Untreated Control | Summary of Adverse Events - Parts 1 and 2 Combined | 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 - Parts 1 and 2 Combined | Subjects with at least one ocular adverse event related to study procedure for the study eye | 0 Participants |
| Untreated Control | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one ocular adverse event for the study eye | 2 Participants |
| Untreated Control | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one non-ocular serious adverse event related to study treatment | 0 Participants |
| Untreated Control | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one non-ocular adverse event related to surgical procedure | 0 Participants |
| Untreated Control | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least 1 ocular SAE event leading to study discontinuation- study eye | 0 Participants |
| Untreated Control | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least 1 ocular SAE related to surgical procedure - study eye | 0 Participants |
| Untreated Control | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one ocular adverse event related to surgical procedure for the study eye | 0 Participants |
| Untreated Control | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one ocular adverse event for the fellow eye | 5 Participants |
| Untreated Control | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one non-ocular serious adverse event related to surgical procedure | 0 Participants |
| Untreated Control | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one non-ocular adverse event related to study treatment | 0 Participants |
| Untreated Control | Summary of Adverse Events - Parts 1 and 2 Combined | Deaths | 2 Participants |
| Untreated Control | Summary of Adverse Events - Parts 1 and 2 Combined | 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 - Parts 1 and 2 Combined | Subjects with at least one ocular adverse event related to study treatment for the study eye | 0 Participants |
| Untreated Control | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one ocular adverse event of special interest for the fellow eye | 1 Participants |
| Untreated Control | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one non-ocular serious adverse event leading to study discontinuation | 2 Participants |
| Untreated Control | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one ocular serious adverse event (SAE) for the study eye | 0 Participants |
| Untreated Control | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one ocular adverse event of special interest for the study eye | 0 Participants |
| Untreated Control | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one non-ocular serious adverse event related to study procedure | 0 Participants |
| Untreated Control | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one ocular serious adverse event for the fellow eye | 0 Participants |
| Untreated Control | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one non-ocular adverse event leading to study discontinuation | 2 Participants |
| Untreated Control | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one ocular adverse event leading to study discontinuation for the study eye | 0 Participants |
| Untreated Control | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one non-ocular serious adverse event | 4 Participants |
| Untreated Control | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one non-ocular adverse event related to study procedure | 0 Participants |
| Untreated Control | Summary of Adverse Events - Parts 1 and 2 Combined | Subjects with at least one non-ocular adverse event | 14 Participants |
Secondary
The Change From Baseline in Geographic Atrophy (GA) at Week 72 and Week 96 - Part 1
The change from baseline to Week 48 in GA area as measured by fundus autofluorescence (FAF)
Time frame: Baseline, Weeks 72 and 96
Population: Full Analysis Set - for randomized participants with a valid measurement without a protocol deviation with impact.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| GT005 Low Dose [2E10 vg] | The Change From Baseline in Geographic Atrophy (GA) at Week 72 and Week 96 - Part 1 | Part 1 Week 72 (n=5,7,9) | 3.643 mm2 | Standard Error 0.9725 |
| GT005 Low Dose [2E10 vg] | The Change From Baseline in Geographic Atrophy (GA) at Week 72 and Week 96 - Part 1 | Part 1 Week 96 (n=6,8,7) | 4.837 mm2 | Standard Error 1.0712 |
| GT005 High Dose [2E11 vg] | The Change From Baseline in Geographic Atrophy (GA) at Week 72 and Week 96 - Part 1 | Part 1 Week 72 (n=5,7,9) | 3.149 mm2 | Standard Error 0.915 |
| GT005 High Dose [2E11 vg] | The Change From Baseline in Geographic Atrophy (GA) at Week 72 and Week 96 - Part 1 | Part 1 Week 96 (n=6,8,7) | 4.074 mm2 | Standard Error 1.0305 |
| Untreated Control | The Change From Baseline in Geographic Atrophy (GA) at Week 72 and Week 96 - Part 1 | Part 1 Week 72 (n=5,7,9) | 1.875 mm2 | Standard Error 0.8273 |
| Untreated Control | The Change From Baseline in Geographic Atrophy (GA) at Week 72 and Week 96 - Part 1 | Part 1 Week 96 (n=6,8,7) | 2.796 mm2 | Standard Error 0.924 |
Comparison: Week 7290% CI: [-0.441, 3.979]mixed model repeated measures
Comparison: Week 7290% CI: [-0.863, 3.412]mixed model repeated measures
Comparison: Week 9690% CI: [-0.386, 4.468]mixed model repeated measures
Comparison: Week 9690% CI: [-1.099, 3.655]mixed model repeated measures