EXPLORE: 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, 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. The trial includes a screening period of up to 8 weeks followed by a 96-week study period. Subjects will be randomised to one of two arms: GT005 or the untreated control group. Part 1 is conducted in a genetically selective sub-group of patients with GA secondary to AMD. Part 2 is conducted in a non-genetically selective sub-group of patients with GA secondary to AMD. 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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EXPLORE: A Phase II, 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 Geographic Atrophy Secondary to Age-related Macular Degeneration

Conditions
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Dry Age-related Macular Degeneration

Intervention / Treatment
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* Drug: GT005; Low Dose
* Drug: GT005; High Dose
* Drug: GT005; Low 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 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) Have GA lesion(s) total size between or equal to 1.25mm2 to 17.5mm2 in the study eye The GA lesion(s) 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, defined as either: Non-exudative/sub-clinical fellow eye CNV identified at Screening, or Known history of fellow eye CNV with either ≥2 years since diagnosis or with no active treatment required in 6 months prior to Screening Have a BCVA of 24 letters (6/95 and 20/320 Snellen acuity equivalent) or better, using ETDRS charts, in the study eye 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 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. 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: Subjects who have a clinical diagnosis of Stargardt Disease or other retinal dystrophies, confirmed by the central reading centre 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 Screening (Visit 1). Yttrium aluminium garnet capsulotomy is permitted if performed >10 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 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 Axial myopia of greater than -8 dioptres in the study eye 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 Have a contraindication to specified protocol corticosteroid regimen 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 Have received a gene or cell therapy at any time 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

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 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.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 - GT005 Low Dose<br>Approximately 25 subjects are planned, with subjects randomised to GT005 Low Dose. | Drug: GT005; Low Dose<br>* Part 1 of the study will test two doses of GT005: Low Dose and High Dose.<br>|
| Experimental: Part 1 - GT005 High Dose<br>Approximately 25 subjects are planned, with subjects randomised to GT005 High Dose. | Drug: GT005; High Dose<br>* Part 1 of the study will test two doses of GT005: Low Dose and High Dose.<br>|
| No Intervention: Part 1 - Untreated control<br>Approximately 25 subjects are planned, with subjects randomised to untreated control. | |
| Experimental: Part 2 - GT005 Low Dose<br>Approximately 116 subjects are planned, with subjects randomised to Part 2 - GT005 Low Dose. | Drug: GT005; Low Dose<br>* Part 2 of the study will test one dose: Low Dose.<br>|
| No Intervention: Part 2 - Untreated control<br>Approximately 54 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 48 in GA area as measured by fundus autofluorescence (FAF) | 48 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) through Week 96 | 96 weeks | 
| Evaluation of the effect of GT005 on retinal anatomical measures | Change in retinal morphology on multimodal imaging through Week 96 | 96 weeks | 
| Evaluation of the effect of GT005 on functional measures | Change in BCVA Score via the early treatment for diabetic retinopathy (ETDRS) chart through Week 96 | 96 weeks | 
| Evaluation of the effect of GT005 on functional measures | Change in low luminance difference (LLD) via the ETDRS chart through Week 96 | 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 through Week 96 | 96 weeks | 
| Evaluation of the effect of GT005 on visual function | Change in functional reading independence (FRI) index through Week 96 | 96 weeks | 
| Evaluation of the effect of GT005 on patient-reported outcomes | Change in quality of life measured on the Visual Functioning Questionnaire-25 (VFQ-25) through Week 96 | 96 weeks | 

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