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

Study Overview
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Brief Summary
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The purpose of this clinical study is 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
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This is a Phase 2, open-label, outcomes-assessor masked, multicentre, randomised, controlled study to evaluate the safety and efficacy of two doses of GT005 administered as a single subretinal injection in subjects with GA secondary to AMD. The trial includes a screening period of up to 8 weeks and a 96-week study period. Subjects will be randomised to one of two groups; GT005 or the untreated control group. This study is terminating early due to the interim analysis demonstrating lack of treatment efficacy. No additional subjects will be randomized or dosed. The trial is not ending early because of medical problems or concerns.

Official Title
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HORIZON: A Phase II, Open-label, Outcomes-assessor Masked, Multicentre, Randomised, Controlled Study to Evaluate the Safety and Efficacy of Two Doses of GT005 Administered as a Single Subretinal Injection in Subjects With Geographic Atrophy Secondary to Dry Age-related Macular Degeneration

Conditions
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Dry Age-related Macular Degeneration

Intervention / Treatment
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* Drug: GT005: Medium Dose
* Drug: GT005: High Dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able and willing to give written informed consent Age ≥55 years a. In Stage 1: Have a clinical diagnosis of GA secondary to AMD in the study eye, as determined by the Investigator, and a diagnosis of AMD in the contralateral eye; b. In Stage 2: Have a clinical diagnosis of GA secondary to AMD in the study eye, as determined by the Investigator, that is non-foveal, as determined by the central reading centre, or has a CFI rare variant genotype and meets inclusion criteria 3a, and a diagnosis of AMD in the contralateral eye (except if monocular) GA lesion(s) within an acceptable size on FAF, in the study eye The GA lesion in the study eye must reside completely within the FAF image Up to 25% of the enrolled study population are permitted to have CNV in the fellow eye Have a BCVA of ≥24 letters (6/95 or 20/320 Snellen acuity equivalent), using ETDRS charts, in the study eye a. In Stage 1: Meet one of the pre-specified AMD genetic subgroup criteria; b. In Stage 2: Genotyping is not required for study eligibility Able to attend all study visits and complete the study procedures Women of child-bearing potential must have a negative pregnancy test within 2 weeks prior to randomisation (not required for postmenopausal women) or provide documentation of being surgically sterilised Exclusion Criteria: a. In Stage 1: Carriers of excluded genetic variants; b. In Stage 2: Subjects are excluded if they have a clinical diagnosis of Stargardt Disease or other retinal dystrophies Have a history, or evidence, of CNV in the study eye Presence of moderate/severe or worse non-proliferative, diabetic retinopathy in the study eye Have history of vitrectomy, sub-macular surgery, or macular photocoagulation in the study eye History of intraocular surgery in the study eye within 12 weeks prior to Visit 1 Have clinically significant cataract that may require surgery during the study period in the study eye Presence of moderate to severe glaucomatous optic neuropathy, uncontrolled intraocular pressure (IOP), despite use of two or more topical agents; or a history of glaucoma-filtering or valve surgery Axial myopia of greater than -8 diopters in the study eye Have received any investigational product for the treatment of GA within the past 6 months or 5 half-lives (whichever is longer), other than nutritional supplements such as the age-related eye disease study (AREDS) formula Have received a gene or cell therapy at any time. Have a contraindication to the protocol specified corticosteroid regimen Are unwilling to use two forms of contraception (one of which being a barrier method) for 90 days post-dosing, if relevant 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 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

Ages Eligible for Study
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Minimum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a Phase II, open-label, outcomes-assessor masked, multicentre, randomised, controlled study to evaluate the safety and efficacy of two doses of GT005 administered as a single subretinal injection in subjects with GA secondary to AMD.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GT005 Medium Dose<br>Approximately 83 subjects are planned, with subjects randomised to GT005 Medium Dose. | Drug: GT005: Medium Dose<br>* The study will test two doses of GT005: Medium Dose and High Dose.<br>|
| Experimental: GT005 High Dose<br>Approximately 83 subjects are planned, with subjects randomised to GT005 High Dose. | Drug: GT005: High Dose<br>* The study will test two doses of GT005: Medium Dose and High Dose.<br>|
| No Intervention: Untreated control<br>Approximately 83 subjects are planned, with subjects randomised to untreated control. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression of geographic atrophy | The change from baseline to Week 72 in GA area as measured by fundus autofluorescence (FAF) | 72 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression of geographic atrophy | The change from baseline through Week 96 in GA area as measured by fundus autofluorescence (FAF) | 96 weeks | 
| Evaluation of the safety and tolerability of GT005 | Frequency of treatment emergent adverse events (AEs) | 96 weeks | 
| Evaluation of the effect of GT005 on retinal anatomical measures | Change in retinal morphology on multimodal imaging | 96 weeks | 
| Evaluation of the effect of GT005 on functional measures | Change in best corrected visual acuity (BCVA) Score via the early treatment for diabetic retinopathy (ETDRS) chart | 96 weeks | 
| Evaluation of the effect of GT005 on functional measures | Change in low luminance difference (LLD) via the ETDRS chart | 96 weeks | 
| Evaluation of the effect of GT005 on visual function | Change in reading performance as assessed by Minnesota low-vision reading test (MNRead) chart | 96 weeks | 
| Evaluation of the effect of GT005 on visual function | Change in functional reading independence (FRI) index | 96 weeks | 
| Evaluation of the effect of GT005 on patient-reported outcomes | Change in quality of life measured on the Visual Function Questionnaire-25 (VFQ-25) | 96 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dry age-related macular degeneration, Geographic atrophy, Retinal disease, Eye disease, Retinal degeneration, Macular atrophy