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
Sponsors
Gyroscope Therapeutics
Eligibility
Sex/Gender
All
Inclusion criteria
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 in the study eye must reside completely within the FAF image 6. Have a BCVA of 24 letters (6/95 and 20/32 Snellen acuity equivalent) or better, using ETDRS charts, in the study eye 7. 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 8. Able to attend all study visits and complete the study procedures 9. 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) 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 7 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 68
Exclusion criteria
Exclusion criteria: 1. Have evidence or history of CNV in either eye 2. Presence of moderate/severe or worse non-proliferative diabetic retinopathy in the study eye 3. Have history of vitrectomy, sub-macular surgery, or macular photocoagulation in the study eye 4. 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 5. Presence of moderate to severe glaucomatous optic neuropathy in the study eye, uncontrolled intraocular pressure (IOP), despite the use of more than two topical agents to control IOP, or a history of glaucoma-filtering or valve surgery 6. Axial myopia of greater than -8 diopters in the study eye 7. 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 8. Have a contraindication to the specified protocol corticosteroid regimen 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 (AREDS) formula 10. Have received a gene or cell therapy at any time 11. Are unwilling to use two forms of contraception (one of which being a barrier method) for 90 days post-dosing, if relevant 12. 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 |
|---|---|
| Main Objective: 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. Primary objective: To evaluate the effect of GT005 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 visual function - To evaluate the effect of GT005 on patient-reported outcomes. Exploratory: - To evaluate local and systemic changes in protein expression. - To evaluate immunogenicity of GT005.;Primary end point(s): Primary: - The change from baseline to Week 48 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): Secondary: • The change from baseline to Week 72 and Week 96 in GA area as measured by fundus autofluorescence (FAF) • Frequency of Treatment Emergent Adverse Events • Change on ophthalmic examination • Change in other parameters of safety, including imaging modalities, Best Corrected Visual Acuity (BCVA), vital signs, and laboratory assessments • Change in retinal microstructures on optical coherence tomography (OCT) • Change in presence of area of nascent GA on OCT • Change in GA morphology on multimodal imaging • Macular Sensitivity as assessed by Mesopic Microperimetry • Change in BCVA Score via the early treatment for diabetic retinopathy (ETDRS) chart • Change in Low Luminance Difference (LLD) via the ETDRS chart • Change in reading performance as assessed by Minnesota Low-Vision Reading Test (MNRead) Chart • Change in Functional Reading Independence (FRI Index) • Change in quality of life measured on the Visual Functioning Questionnaire-25 (VFQ-25);Timepoint(s) of evaluation of this end point: • AEs-Screening, Randomisation, pre & post surgery/surgery, Day3, Weeks 1, 2, 5, 8, 12, 24, 36, 48, 72, 96 (EoS), Early termination visit (ETV) •Ophthalmic exam-Screening, pre & post surgery, Wks 1, 5 to 96, ETV •Other parameters of safety-Screening, pre & post surgery, Wks 1, 5, 12, 24, 36, 48, 72,96 ETV •OCT-Screening, post surgery, Wks 1,5 to 96, ETV •Colour fundus photog-Screening, Wk 5, 48 to 96 ETV •Microperimetry-Screening, pre surgery, Wks 12 to 96, ETV • BCVA with ETDRS-Screening, pre surgery, Wks 1, 5, 8, 12, 24, 36, 48,72, 96 ETV •LLD with ETDRS-Screening, pre surgery, Wks 12, 24, 36, 48, 72, 96, ETV • Visual acuity-D1, •MNRead-Screening, Wks 24, 36, 48, 72, 96 ETV •FRI Index-Screening, Wks 24, 36, 48, 72, 96 ETV •VFQ-25-Screening, Wks 24, 36, 48, 72, 96 ETV | — |
Countries
Australia, France, Germany, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactKathryn Parsley
Gyroscope Therapeutics
Outcome results
None listed