Age-related Macular Degeneration (AMD) presents as a progressive loss of vision in the centre of the retina (the macula) resulting in a blurred area or blank spot in the centre of vision. The primary clinical characteristic of late stage AMD is atrophy of the Retinal Pigment Epithelium, known as macular atrophy due to AMD, which leads to the gradual degeneration of nearby photoreceptors, resulting in thinning of the retina and a progressive visual impairment. MedDRA version: 20.0 Level: LLT Cla
Conditions
Interventions
Product Name: Recombinant, non-replicating AAV2 expressing human CFI
Product Code: GT005
Pharmaceutical Form: Suspension for injection
Current Sponsor code: GT005
Other descriptive name: GT005
Concent
Sponsors
Gyroscope Therapeutics Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able and willing to give written informed consent 2. Age =55 years 3. a. In Stage 1: Have a clinical diagnosis of GA secondary to AMD in the study eye, as determined by the Investigator, and a diagnosis of AMD in the contralateral eye (except if the subject is monocular) 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 associated with normal or low serum CFI, and meets inclusion criteria 3a (e.g., foveal or non-foveal GA), 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 1.25 mm2 to 17.5 mm2 in the study eye 5. The GA lesion in the study eye must reside completely within the FAF image 6. Up to 25% of the enrolled study population are permitted to have CNV in the fellow eye, defined as either: a. Non-exudative/sub-clinical fellow eye CNV identified at Screening, or b. 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 or 20/320 Snellen acuity equivalent), using ETDRS charts, in the study eye 8. Meet one of the following AMD genetic subgroup criteria, as reviewed and confirmed by the Sponsor, and be allocated to one of the following groups below: a. In Stage 1 • Group 1: Subjects carrying a CFI rare variant genotype (minor allele frequency =1%) previously associated with normal serum CFI or subjects carrying an unreported CFI rare variant genotype that has tested to have normal serum CFI. • Group 2: Complement rare: Rare coding variant in either C3, CFB, CFH, CD59, or CD46 genes with a minor allele frequency =2% that is enriched in AMD and/or predicted to be damaging in silico • Group 3: CFH common: Carriers of one or two copies of either the C allele of rs1329428, or the C allele of rs1061170 (also excluding carriers of T allele of rs10033900) • Group 4: CFI common: Carriers of one or two copies of the T allele of rs10033900 b. In Stage 2: Genotyping is not required for study eligibility 9. Able to attend all study visits and complete the study procedures 10. Women of child-bearing potential must have a negative pregnancy test within 2 weeks prior to randomisation or provide documentation of being surgically sterilised. 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) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 13 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 167
Exclusion criteria
Exclusion criteria: 1. Any carriers of the following genetic variants: a. In Stage 1 ABCA4 rare (minor allele frequency =1%) coding variants predicted to be damaging in silico, either biallelic, or monoallelic in combination with a minor allele of a hypomorphic variant (rs1801466 or rs6657239) b. In Stage 2, subjects are excluded if they have a clinical diagnosis of Stargardt Disease or other retinal dystrophies, as 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 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, uncontrolled intraocular pressure (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 diopters in the study eye 9. Have received any investigational product for the treatment of GA within the past 6 months, or 5 half-lives (whichever is longer) other than nutritional supplements such as the age-related eye disease study formula 10. Have received a gene or cell therapy at any time 11. Have a contraindication to the corticosteroid regimen 12. Are unwilling to use two forms of contraception (one of which being a barrier method) for 90 days post-dosing, if relevant 13. Active malignancy within the past 12 months, except for: appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or prostate cancer with a stable prostate-specific antigen (PSA) =12 months 14. Have any other significant ocular or non-ocular medical or psychiatric condition which, in the opinion of the Investigator, may either put the subject at risk or may influence the results of the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The overall objective of the study is to evaluate the safety and efficacy (anatomical and functional visual outcomes) of two doses of GT005 in subjects with GA due to AMD. Primary objective: To demonstrate the effect of GT005 vs untreated control on the progression of GA in subjects with GA due to AMD ;Secondary Objective: Secondary: - To evaluate the effect of GT005 on the progression of GA in subjects with GA due to AMD - To evaluate the safety and tolerability of GT005 - To evaluate the effect of GT005 on retinal anatomical measures - To evaluate the effect of GT005 on functional measures - To evaluate the effect of GT005 on visional function - To evaluate the effect of GT005 on patient-reported outcomes - To evaluate the effect of GT005 on the progression of GA due to AMD, in each genetically defined subgroup(s) Exploratory: - To evaluate the effect of GT005 on macular sensitivity - To evaluate the effect of GT005 on the progression of GA due to AMD, in each genetically defined subgroup(s) - To further evaluate the safety and tolerability of GT005 - To evaluate immunogenicity of GT005 - To evaluate local and systemic changes in protein expression - To evaluate polygenic risk scores (derived of complement genetic variants);Primary end point(s): Primary: - The change from baseline to Week 72 in GA area as measured by fundus autofluorescence (FAF);Timepoint(s) of evaluation of this end point: Screening, Weeks 12, 24, 36, 48, 72, 96 (EoS), Early termination visit (ETV) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • The change from baseline through Week 96 in GA area as measured by FAF • Frequency of treatment emergent adverse events (AEs) through Week 96 • Change in retinal morphology on multimodal imaging through Week 96 • Change in Best corrected visual acuity (BCVA) score via the early treatment for diabetic retinopathy (ETDRS) chart through Week 96 • Change in low luminance difference (LLD) via the ETDRS chart through Week 96 • Change in reading performance as assessed by Minnesota low-vision reading test (MNRead) chart through Week 96 • Change in functional reading independence (FRI) index through Week 96 • Change in quality of life measured on the visual functioning questionnaire-25 (VFQ 25) through Week 96 ;Timepoint(s) of evaluation of this end point: • AEs-Screen, Randomisation, pre & post surgery/surgery, Day3, Wk 1, 2, 5, 8, 12, 24, 36, 48,72,96 (EoS), ETV •Ophthalmic exam-Screen, post surgery, Wk 1, 5, 8, 12, 24, 36, 48,72,96,ETV •OCT-Screen, post surgery, Wk 1,5, 12, 24, 36, 48, 72,96 ETV •CFP-Screen, Wk 5, 48,72,96,ETV •Microperimetry-Screen, Wk 12, 24, 36, 48,76,96, ETV •BCVA with ETDRS-Screen, Wk 1, 5, 8, 12, 24, 36, 48,72,96 ETV •LLVA with ETDRS for LLD-Screen, Wk 12, 24, 36, 48,72,96 ETV •MNRead, FRI Index, and VFQ-25- At Screen, Wk 24, 36, 48, 72, 96, ETV •Vital signs – Screen, pre & post surgery, Wk 1, 5, 24, 48, 72, 96, ETV •Samples for Proteomics (blood or vitreous) – Screen, Pre surgery, Surgery, Wk 12, 24, 48, 96, ETV •Immunogenicity – Pre surgery, Wk 5, 12, 24, 48, 96, ETV | — |
Countries
Australia, France, Germany, Ireland, Poland, Spain, United Kingdom, United States
Contacts
Public ContactKathryn Parsley
Gyroscope Therapeutics
Outcome results
None listed