Trial Outcomes & Findings for HORIZON: A Phase II Study to Evaluate the Safety and Efficacy of Two Doses of GT005 (NCT NCT04566445)

NCT ID: NCT04566445

Last Updated: 2025-07-10

Results Overview

GA area as measured by fundus autofluorescence (FAF)

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

255 participants

Primary outcome timeframe

Baseline, Weeks 12, 24, 36, 48 and 72

Results posted on

2025-07-10

Participant Flow

This was a 3-arm study conducted in 2 stages. Results are reported per the 3 treatment arms. Stage 1 and Stage 2 results were combined since the study population and study treatments were the same in both Stage 1 and Stage 2; In Stage 1, participants were enrolled with both foveal and non-foveal geographic atrophy and in Stage 2, participants were enrolled with non-foveal geographic atrophy to enrich the number of participants with non-foveal geographic atrophy.

The study design with 3 arms was the same for both Stage 1 and 2. Analysis was performed following the statistical analysis plan to combine Stage 1 and 2 results, and to report results per the 3 unique treatment arms.

Participant milestones

Participant milestones
Measure	GT005 Medium Dose [5E10 vg] GT005 Medium dose \[5E10 vg\]	GT005 High Dose [2E11 vg] GT005 High dose \[2E11 vg\]	Untreated Control Untreated control
Overall Study STARTED	87	86	82
Overall Study Stage 1 (Foveal and Non-foveal Geographic Atrophy)	64	62	61
Overall Study Stage 2 (Non-foveal Geographic Atrophy)	23	24	21
Overall Study COMPLETED	54	51	35
Overall Study NOT COMPLETED	33	35	47

Reasons for withdrawal

Reasons for withdrawal
Measure	GT005 Medium Dose [5E10 vg] GT005 Medium dose \[5E10 vg\]	GT005 High Dose [2E11 vg] GT005 High dose \[2E11 vg\]	Untreated Control Untreated control
Overall Study Death	4	1	1
Overall Study Lost to Follow-up	3	1	1
Overall Study Study terminated by sponsor	11	17	32
Overall Study Withdrawal by Subject	12	14	13
Overall Study Randomized but not treated due to AE	2	1	0
Overall Study Adverse Event	1	1	0

Baseline Characteristics

HORIZON: A Phase II Study to Evaluate the Safety and Efficacy of Two Doses of GT005

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GT005 Medium Dose [5E10 vg] n=87 Participants GT005 Medium dose \[5E10 vg\]	GT005 High Dose [2E11 vg] n=86 Participants GT005 High dose \[2E11 vg\]	Untreated Control n=82 Participants Untreated control	Total n=255 Participants Total of all reporting groups
Age, Continuous	77.6 Years STANDARD_DEVIATION 7.33 • n=5 Participants	77.6 Years STANDARD_DEVIATION 7.60 • n=7 Participants	77.8 Years STANDARD_DEVIATION 6.83 • n=5 Participants	77.7 Years STANDARD_DEVIATION 7.24 • n=4 Participants
Sex: Female, Male Female	52 Participants n=5 Participants	61 Participants n=7 Participants	53 Participants n=5 Participants	166 Participants n=4 Participants
Sex: Female, Male Male	35 Participants n=5 Participants	25 Participants n=7 Participants	29 Participants n=5 Participants	89 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	87 Participants n=5 Participants	80 Participants n=7 Participants	80 Participants n=5 Participants	247 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	5 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline, Weeks 12, 24, 36, 48 and 72

Population: Full Analysis Set - for participants with a valid measurement without a protocol deviation with impact.

GA area as measured by fundus autofluorescence (FAF)

Outcome measures

Outcome measures
Measure	GT005 Medium Dose [5E10 vg] n=75 Participants GT005 Medium dose \[5E10 vg\]	GT005 High Dose [2E11 vg] n=75 Participants GT005 High dose \[2E11 vg\]	Untreated Control n=72 Participants Untreated control
The Change From Baseline to Week 72 in Geographic Atrophy (GA) Week 12 (n=75,71,72)	0.730 mm^2 Standard Error 0.0625	0.752 mm^2 Standard Error 0.0634	0.667 mm^2 Standard Error 0.0647
The Change From Baseline to Week 72 in Geographic Atrophy (GA) Week 24 (n=72,75,71)	1.151 mm^2 Standard Error 0.0833	1.260 mm^2 Standard Error 0.0831	1.054 mm^2 Standard Error 0.0860
The Change From Baseline to Week 72 in Geographic Atrophy (GA) Week 36 (n=66,66,71)	1.728 mm^2 Standard Error 0.1488	1.955 mm^2 Standard Error 0.1503	1.531 mm^2 Standard Error 0.1528
The Change From Baseline to Week 72 in Geographic Atrophy (GA) Week 48 (n=64,68,65)	2.098 mm^2 Standard Error 0.1841	2.535 mm^2 Standard Error 0.1853	2.047 mm^2 Standard Error 0.1896
The Change From Baseline to Week 72 in Geographic Atrophy (GA) Week 72 (n=56,51,54)	3.225 mm^2 Standard Error 0.2337	3.421 mm^2 Standard Error 0.2369	2.919 mm^2 Standard Error 0.2412

SECONDARY outcome

Timeframe: Baseline, Week 96

Population: Full Analysis Set - for participants with a valid measurement without a protocol deviation with impact.

GA area as measured by fundus autofluorescence (FAF)

Outcome measures

Outcome measures
Measure	GT005 Medium Dose [5E10 vg] n=44 Participants GT005 Medium dose \[5E10 vg\]	GT005 High Dose [2E11 vg] n=39 Participants GT005 High dose \[2E11 vg\]	Untreated Control n=32 Participants Untreated control
The Change From Baseline at Week 96 in Geographic Atrophy (GA)	4.414 mm2 Standard Error 0.3109	4.607 mm2 Standard Error 0.3167	3.769 mm2 Standard Error 0.3286

SECONDARY outcome

Timeframe: Adverse events are reported from randomization to the end of study, at Week 96, up to a maximum timeframe of approximately 96 weeks.

Population: Full Analysis Set - all randomized participants

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.

Outcome measures

Outcome measures
Measure	GT005 Medium Dose [5E10 vg] n=87 Participants GT005 Medium dose \[5E10 vg\]	GT005 High Dose [2E11 vg] n=86 Participants GT005 High dose \[2E11 vg\]	Untreated Control n=82 Participants Untreated control
Summary of Adverse Events Subjects with at least one non-ocular adverse event leading to study discontinuation	5 Participants	2 Participants	1 Participants
Summary of Adverse Events Subjects with at least one ocular adverse event of special interest for the study eye	19 Participants	31 Participants	3 Participants
Summary of Adverse Events Subjects with at least one ocular adverse event of special interest for the fellow eye	3 Participants	3 Participants	1 Participants
Summary of Adverse Events Subjects with at least one ocular serious adverse event (SAE) for the study eye	2 Participants	5 Participants	0 Participants
Summary of Adverse Events Subjects with at least one ocular serious adverse event for the fellow eye	0 Participants	0 Participants	0 Participants
Summary of Adverse Events Subjects with at least one non-ocular serious adverse event	20 Participants	22 Participants	10 Participants
Summary of Adverse Events Subjects with at least one ocular serious adverse event related to study treatment for the study eye	0 Participants	0 Participants	0 Participants
Summary of Adverse Events Subjects with at least one non-ocular serious adverse event related to study treatment	0 Participants	0 Participants	0 Participants
Summary of Adverse Events Subjects with at least one ocular SAE related to surgical procedure for the study eye	1 Participants	4 Participants	0 Participants
Summary of Adverse Events Subjects with at least one non-ocular serious adverse event related to surgical procedure	0 Participants	0 Participants	0 Participants
Summary of Adverse Events Subjects with at least one ocular serious adverse event related to study procedure for the study eye	1 Participants	1 Participants	0 Participants
Summary of Adverse Events Subjects with at least one non-ocular serious adverse event related to study procedure	0 Participants	0 Participants	0 Participants
Summary of Adverse Events Subjects with at least one ocular SAE leading to study discontinuation for the study eye	0 Participants	0 Participants	0 Participants
Summary of Adverse Events Subjects with at least one non-ocular serious adverse event leading to study discontinuation	5 Participants	2 Participants	1 Participants
Summary of Adverse Events Deaths	4 Participants	1 Participants	1 Participants
Summary of Adverse Events Subjects with at least one non-ocular adverse event related to surgical procedure	0 Participants	0 Participants	0 Participants
Summary of Adverse Events Subjects with at least one ocular adverse event for the study eye	66 Participants	65 Participants	15 Participants
Summary of Adverse Events Subjects with at least one ocular adverse event for the fellow eye	32 Participants	35 Participants	14 Participants
Summary of Adverse Events Subjects with at least one non-ocular adverse event	63 Participants	59 Participants	44 Participants
Summary of Adverse Events Subjects with at least one ocular adverse event related to study treatment for the study eye	13 Participants	21 Participants	0 Participants
Summary of Adverse Events Subjects with at least one non-ocular adverse event related to study treatment	0 Participants	0 Participants	0 Participants
Summary of Adverse Events Subjects with at least one ocular adverse event related to surgical procedure for the study eye	48 Participants	48 Participants	0 Participants
Summary of Adverse Events Subjects with at least one ocular adverse event related to study procedure for the study eye	8 Participants	9 Participants	0 Participants
Summary of Adverse Events Subjects with at least one non-ocular adverse event related to study procedure	0 Participants	2 Participants	0 Participants
Summary of Adverse Events Subjects with at least one ocular adverse event leading to study discontinuation for the study eye	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Adverse events are reported from randomization to the end of study, at Week 96, up to a maximum timeframe of approximately 96 weeks.

Population: Full Analysis Set - all randomized participants

Outcome measures

Outcome measures
Measure	GT005 Medium Dose [5E10 vg] n=87 Participants GT005 Medium dose \[5E10 vg\]	GT005 High Dose [2E11 vg] n=86 Participants GT005 High dose \[2E11 vg\]	Untreated Control n=82 Participants Untreated control
Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye -Posterior capsule opacification	3 Participants	4 Participants	2 Participants
Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye -Anterior chamber cell	4 Participants	4 Participants	0 Participants
Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye -Eye irritation	6 Participants	2 Participants	0 Participants
Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye Subjects with at least one event	66 Participants	65 Participants	15 Participants
Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye Eye disorders	65 Participants	62 Participants	14 Participants
Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye -Cataract	21 Participants	20 Participants	3 Participants
Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye -Retinal pigmentation	12 Participants	22 Participants	0 Participants
Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye -Conjunctival haemorrhage	18 Participants	12 Participants	1 Participants
Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye -Retinal haemorrhage	8 Participants	10 Participants	2 Participants
Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye -Eye pain	5 Participants	7 Participants	0 Participants
Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye -Ocular hypertension	6 Participants	6 Participants	0 Participants
Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye -Punctate keratitis	6 Participants	6 Participants	0 Participants
Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye -Retinal tear	5 Participants	6 Participants	0 Participants
Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye -Dry eye	4 Participants	4 Participants	1 Participants
Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye -Vitreous haemorrhage	2 Participants	6 Participants	0 Participants
Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye -Choroidal neovascularisation	2 Participants	3 Participants	2 Participants
Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye -Vitreous floaters	3 Participants	4 Participants	0 Participants
Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye -Cataract nuclear	3 Participants	3 Participants	0 Participants
Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye -Retinal detachment	2 Participants	4 Participants	0 Participants
Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye -Corneal oedema	1 Participants	4 Participants	0 Participants
Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye -Diplopia	4 Participants	1 Participants	0 Participants
Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye -Eye pruritus	1 Participants	4 Participants	0 Participants
Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye -Foreign body sensation in eyes	3 Participants	2 Participants	0 Participants
Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye -Iritis	4 Participants	1 Participants	0 Participants
Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye -Visual impairment	2 Participants	3 Participants	0 Participants
Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye Investigations	11 Participants	2 Participants	0 Participants
Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye -Intraocular pressure increased	1 Participants	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Adverse events are reported from randomization to the end of study, at Week 96, up to a maximum timeframe of approximately 96 weeks.

Population: Full Analysis Set - all randomized participants

Outcome measures

Outcome measures
Measure	GT005 Medium Dose [5E10 vg] n=87 Participants GT005 Medium dose \[5E10 vg\]	GT005 High Dose [2E11 vg] n=86 Participants GT005 High dose \[2E11 vg\]	Untreated Control n=82 Participants Untreated control
Non-ocular AEs Occurring in ≥2% of Subjects	63 Participants	59 Participants	44 Participants

SECONDARY outcome

Timeframe: Baseline, Weeks 5, 12, 24, 36, 48, 72 and 96

Population: Full Analysis Set - for participants with a valid measurement without a protocol deviation with impact.

Change in retinal morphology on multimodal imaging. For the untreated control group, there were no protocol-specified visits at Week 5.

Outcome measures

Outcome measures
Measure	GT005 Medium Dose [5E10 vg] n=75 Participants GT005 Medium dose \[5E10 vg\]	GT005 High Dose [2E11 vg] n=78 Participants GT005 High dose \[2E11 vg\]	Untreated Control n=74 Participants Untreated control
Change in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence Week 5 (n=23,24,0)	23 Participants	23 Participants	—
Change in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence Week 12 (n=75,73,74)	74 Participants	73 Participants	73 Participants
Change in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence Week 24 (n=75,78,72)	72 Participants	78 Participants	71 Participants
Change in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence Week 36 (n=70,70, 71)	66 Participants	69 Participants	70 Participants
Change in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence Week 48 (n=67,72,68)	67 Participants	71 Participants	68 Participants
Change in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence Week 72 (n=61, 62,59)	60 Participants	60 Participants	56 Participants
Change in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence Week 96 (n=52,49, 34)	50 Participants	48 Participants	33 Participants

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 5, 8, 12, 24, 36, 48, 72 and 96

Population: Full Analysis Set - for participants with a valid measurement without a protocol deviation with impact.

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.

Outcome measures

Outcome measures
Measure	GT005 Medium Dose [5E10 vg] n=81 Participants GT005 Medium dose \[5E10 vg\]	GT005 High Dose [2E11 vg] n=79 Participants GT005 High dose \[2E11 vg\]	Untreated Control n=73 Participants Untreated control
Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart Week 1 (n=81,78,0)	-2.0 Letters read Standard Error 1.54	-7.0 Letters read Standard Error 1.56	—
Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart Week 5 (n=81,78,0)	-0.8 Letters read Standard Error 0.88	-3.3 Letters read Standard Error 0.89	—
Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart Week 8 (n=79,77,0)	-0.1 Letters read Standard Error 0.85	-1.7 Letters read Standard Error 0.86	—
Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart Week 12 (n=79,79,73)	-1.1 Letters read Standard Error 0.91	-2.5 Letters read Standard Error 0.91	-0.7 Letters read Standard Error 0.96
Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart Week 24 (n=78,78,71)	-2.7 Letters read Standard Error 1.03	-6.3 Letters read Standard Error 1.03	-1.1 Letters read Standard Error 1.09
Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart Week 36 (75,74,72)	-2.5 Letters read Standard Error 1.24	-7.7 Letters read Standard Error 1.25	-3.0 Letters read Standard Error 1.30
Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart Week 48 (n=73,75,69)	-2.6 Letters read Standard Error 1.48	-7.3 Letters read Standard Error 1.46	-5.3 Letters read Standard Error 1.54
Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart Week 72 (n=63, 70, 58)	-4.1 Letters read Standard Error 1.54	-7.9 Letters read Standard Error 1.50	-8.8 Letters read Standard Error 1.61
Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart Week 96 (n=54,51,35)	-5.5 Letters read Standard Error 1.78	-10.0 Letters read Standard Error 1.78	-12.7 Letters read Standard Error 2.02

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24, 36, 48, 72 and 96

Population: Full Analysis Set - for participants with a valid measurement without a protocol deviation with impact.

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.

Outcome measures

Outcome measures
Measure	GT005 Medium Dose [5E10 vg] n=79 Participants GT005 Medium dose \[5E10 vg\]	GT005 High Dose [2E11 vg] n=76 Participants GT005 High dose \[2E11 vg\]	Untreated Control n=74 Participants Untreated control
Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, 48, 72 and 96, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart Week 12	-0.6 Letters read Standard Deviation 7.59	-1.1 Letters read Standard Deviation 9.63	1.2 Letters read Standard Deviation 9.51
Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, 48, 72 and 96, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart Week 24 (n=78,75,71)	-0.6 Letters read Standard Deviation 10.10	-2.5 Letters read Standard Deviation 12.73	0.5 Letters read Standard Deviation 12.01
Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, 48, 72 and 96, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart Week 36 (n=75,72,71)	0.0 Letters read Standard Deviation 9.90	-2.6 Letters read Standard Deviation 13.40	-0.1 Letters read Standard Deviation 11.12
Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, 48, 72 and 96, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart Week 48 (n=73,73,69)	-0.5 Letters read Standard Deviation 10.31	-1.5 Letters read Standard Deviation 15.18	-0.4 Letters read Standard Deviation 12.93
Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, 48, 72 and 96, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart Week 72 (n=63,67,58)	-0.5 Letters read Standard Deviation 13.15	-5.2 Letters read Standard Deviation 17.24	-2.5 Letters read Standard Deviation 14.93
Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, 48, 72 and 96, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart Week 96 (n=54,49,35)	-3.1 Letters read Standard Deviation 16.11	-2.2 Letters read Standard Deviation 13.48	-5.9 Letters read Standard Deviation 16.82

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24, 36, 48, 72 and 96

Population: Full Analysis Set - for participants with a valid measurement without a protocol deviation with impact.

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.

Outcome measures

Outcome measures
Measure	GT005 Medium Dose [5E10 vg] n=73 Participants GT005 Medium dose \[5E10 vg\]	GT005 High Dose [2E11 vg] n=72 Participants GT005 High dose \[2E11 vg\]	Untreated Control n=65 Participants Untreated control
Reading Performance, Measured as the MRS (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart: Summary Statistics for Change From Baseline by Visit for the Study Eye Week 24 (n=73,72,65)	-15.756 Words read per minute Standard Deviation 32.7268	-12.368 Words read per minute Standard Deviation 43.2054	-15.769 Words read per minute Standard Deviation 40.5051
Reading Performance, Measured as the MRS (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart: Summary Statistics for Change From Baseline by Visit for the Study Eye Week 36 (n=71,70,65)	-18.488 Words read per minute Standard Deviation 54.7913	-15.673 Words read per minute Standard Deviation 31.7802	-3.689 Words read per minute Standard Deviation 94.1057
Reading Performance, Measured as the MRS (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart: Summary Statistics for Change From Baseline by Visit for the Study Eye Week 48 (n=69,67,62)	-20.734 Words read per minute Standard Deviation 36.4110	-6.678 Words read per minute Standard Deviation 49.0844	-17.297 Words read per minute Standard Deviation 56.8547
Reading Performance, Measured as the MRS (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart: Summary Statistics for Change From Baseline by Visit for the Study Eye Week 72 (n=57,64,53)	-24.485 Words read per minute Standard Deviation 45.8525	-20.798 Words read per minute Standard Deviation 39.6796	-26.121 Words read per minute Standard Deviation 40.8016
Reading Performance, Measured as the MRS (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart: Summary Statistics for Change From Baseline by Visit for the Study Eye Week 96 (n=48,47,29)	-24.678 Words read per minute Standard Deviation 44.7777	-25.178 Words read per minute Standard Deviation 39.7216	-19.242 Words read per minute Standard Deviation 45.0703

SECONDARY outcome

Timeframe: Baseline, Weeks 24, 36, 48, 72 and 96

Population: Full Analysis Set - for participants with a valid measurement without a protocol deviation with impact.

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.

Outcome measures

Outcome measures
Measure	GT005 Medium Dose [5E10 vg] n=77 Participants GT005 Medium dose \[5E10 vg\]	GT005 High Dose [2E11 vg] n=75 Participants GT005 High dose \[2E11 vg\]	Untreated Control n=67 Participants Untreated control
Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index Week 24 (n=77,75,67)	-0.4 Scores on a scale Standard Deviation 5.20	-1.4 Scores on a scale Standard Deviation 4.74	-0.1 Scores on a scale Standard Deviation 3.98
Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index Week 36 (n=74,72,66)	-0.8 Scores on a scale Standard Deviation 4.64	-1.1 Scores on a scale Standard Deviation 4.31	-0.1 Scores on a scale Standard Deviation 4.67
Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index Week 48 (n=70,73,65)	-0.3 Scores on a scale Standard Deviation 4.76	-1.4 Scores on a scale Standard Deviation 4.87	-0.2 Scores on a scale Standard Deviation 4.50
Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index Week 72 (n=63,69,58)	-0.8 Scores on a scale Standard Deviation 4.93	-1.3 Scores on a scale Standard Deviation 5.19	-1.5 Scores on a scale Standard Deviation 5.37
Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index Week 96 (n=54,51,32)	-1.4 Scores on a scale Standard Deviation 5.57	-1.4 Scores on a scale Standard Deviation 4.41	-1.1 Scores on a scale Standard Deviation 5.11

SECONDARY outcome

Timeframe: Baseline, Weeks 24, 36, 48, 72 and 96

Population: Full Analysis Set - for participants with a valid measurement without a protocol deviation with impact.

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.

Outcome measures

Outcome measures
Measure	GT005 Medium Dose [5E10 vg] n=77 Participants GT005 Medium dose \[5E10 vg\]	GT005 High Dose [2E11 vg] n=78 Participants GT005 High dose \[2E11 vg\]	Untreated Control n=67 Participants Untreated control
Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score Week 24 (n=77,78,67)	-1.466 Scores on a scale Standard Deviation 12.8742	-2.289 Scores on a scale Standard Deviation 12.3295	-1.270 Scores on a scale Standard Deviation 11.2063
Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score Week 36 (n=74,73,66)	-1.955 Scores on a scale Standard Deviation 11.5060	-3.479 Scores on a scale Standard Deviation 12.0848	-2.273 Scores on a scale Standard Deviation 12.2395
Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score Week 48 (n=70,74,65)	-2.501 Scores on a scale Standard Deviation 12.9563	-3.113 Scores on a scale Standard Deviation 11.9974	-4.403 Scores on a scale Standard Deviation 14.2465
Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score Week 72 (n=63,69,54)	-4.232 Scores on a scale Standard Deviation 14.6259	-3.432 Scores on a scale Standard Deviation 11.3840	-6.583 Scores on a scale Standard Deviation 15.5133
Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score Week 96 (n=54,51,33)	-6.341 Scores on a scale Standard Deviation 14.4187	-7.718 Scores on a scale Standard Deviation 10.9016	-6.804 Scores on a scale Standard Deviation 15.4812

Adverse Events

GT005@Medium Dose@[5E10 vg]

Serious events: 22 serious events

Other events: 76 other events

Deaths: 4 deaths

GT005@High Dose@[2E11 vg]

Serious events: 25 serious events

Other events: 75 other events

Deaths: 1 deaths

Untreated Control

Serious events: 10 serious events

Other events: 50 other events

Deaths: 1 deaths

Overall

Serious events: 57 serious events

Other events: 201 other events

Deaths: 6 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: + 1 862 778 8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER