EXPLORE: A Phase II Study to Evaluate the Safety and Efficacy of Two Doses of GT005
- Conditions
- Dry Age-related Macular Degeneration
- Interventions
- Drug: GT005; High DoseDrug: GT005; Low Dose
- Registration Number
- NCT04437368
- Lead Sponsor
- Gyroscope Therapeutics Limited
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 98
-
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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1 - GT005 High Dose GT005; High Dose Approximately 25 subjects are planned, with subjects randomised to GT005 High Dose. Part 1 - GT005 Low Dose GT005; Low Dose Approximately 25 subjects are planned, with subjects randomised to GT005 Low Dose. Part 2 - GT005 Low Dose GT005; Low Dose Approximately 116 subjects are planned, with subjects randomised to Part 2 - GT005 Low Dose.
- Primary Outcome Measures
Name Time Method Progression of geographic atrophy 48 weeks The change from baseline to Week 48 in GA area as measured by fundus autofluorescence (FAF)
- Secondary Outcome Measures
Name Time Method Progression of geographic atrophy 96 weeks The change from baseline through Week 96 in GA area as measured by fundus autofluorescence (FAF)
Evaluation of the effect of GT005 on retinal anatomical measures 96 weeks Change in retinal morphology on multimodal imaging through Week 96
Evaluation of the effect of GT005 on functional measures 96 weeks Change in low luminance difference (LLD) via the ETDRS chart through Week 96
Evaluation of the safety and tolerability of GT005 96 weeks Frequency of treatment emergent adverse events (AEs) through Week 96
Evaluation of the effect of GT005 on visual function 96 weeks Change in functional reading independence (FRI) index through Week 96
Evaluation of the effect of GT005 on patient-reported outcomes 96 weeks Change in quality of life measured on the Visual Functioning Questionnaire-25 (VFQ-25) through Week 96
Trial Locations
- Locations (55)
Mid Atlantic Retina
🇺🇸Philadelphia, Pennsylvania, United States
Midwest Eye Institute Northside
🇺🇸Indianapolis, Indiana, United States
Department of Ophthalmology UW Medicine
🇺🇸Seattle, Washington, United States
Retina Associates of Southern California
🇺🇸Huntington Beach, California, United States
Byers Eye Institute at Stanford
🇺🇸Palo Alto, California, United States
Retina Consultants San Diego
🇺🇸Poway, California, United States
Bascom Palmer Eye Institute
🇺🇸Miami, Florida, United States
University Retina Macula Associates PC
🇺🇸Lemont, Illinois, United States
Retina Vitreous Associates of Florida
🇺🇸Saint Petersburg, Florida, United States
Southeast Retina Center
🇺🇸Augusta, Georgia, United States
Wolfe Eye Clinic
🇺🇸West Des Moines, Iowa, United States
Ophthalmic Consultants of Boston (OCB)
🇺🇸Boston, Massachusetts, United States
The Retina Care Center
🇺🇸Baltimore, Maryland, United States
Vision Research Center Eye Associates of New Mexico
🇺🇸Albuquerque, New Mexico, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Retina Associates of Western New York
🇺🇸Rochester, New York, United States
Cincinnati Eye Institute
🇺🇸Cincinnati, Ohio, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Oregon Retina
🇺🇸Eugene, Oregon, United States
Erie Retinal Surgery, INC
🇺🇸Erie, Pennsylvania, United States
Texas Retina Associates
🇺🇸Dallas, Texas, United States
Retina Consultants of Houston-TMC
🇺🇸Bellaire, Texas, United States
Universitaetsklinikum Schleswig-Holstein Campus Lübeck
🇩🇪Lübeck, Schleswig-Holstein, Germany
Sydney Hospital and Sydney Eye Hospital
🇦🇺Sydney, Australia
Centre Paradis Monticelli
🇫🇷Marseille, Alpes-Cote d'Azur, France
Universitaetsklinikum Bonn
🇩🇪Bonn, Germany
Clinica Oftalvist Valencia
🇪🇸Valencia, Spain
Internationale Innovative Ophthalmochirurgie
🇩🇪Düsseldorf, Germany
St. Franziskus-Hospital
🇩🇪Münster, Germany
Universitatsklinikum Tübingen
🇩🇪Tübingen, Germany
Oftalmika Spolka z ograniczona odpowiedzialnoscia
🇵🇱Bydgoszcz, Poland
Clinica Universidad de Navarra - Pamplona
🇪🇸Pamplona, Navarra, Spain
Hospital La Arruzafa
🇪🇸Córdoba, Spain
Clinica Baviera
🇪🇸Madrid, Spain
St.Paul's Eye Unit
🇬🇧Liverpool, United Kingdom
Moorfields Eye Hospital - NHS Foundation Trust
🇬🇧London, United Kingdom
Sunderland Eye Infirmary
🇬🇧Sunderland, United Kingdom
The Retina Clinic London
🇬🇧London, United Kingdom
Sheffield Teaching Hospitals NHS Foundation Trust
🇬🇧Sheffield, United Kingdom
Stichting Radboud Universitair Medisch Centrum
🇳🇱Nijmegen, Netherlands
Charles Retina Institute
🇺🇸Memphis, Tennessee, United States
Sierra Eye Associates
🇺🇸Reno, Nevada, United States
West Virginia University
🇺🇸Morgantown, West Virginia, United States
CHU Hôpital F. Mitterrand
🇫🇷Dijon, Bourgogne-Franche-Comté, France
Southeastern Retina Associates, PC
🇺🇸Knoxville, Tennessee, United States
The University of Melbourne - The Centre for Eye Research Australia (CERA)
🇦🇺Melbourne E., Victoria, Australia
Hospital Universitari General de Catalunya
🇪🇸Sant Cugat Del Vallès, Barcelona, Spain
Bristol Eye Hospital
🇬🇧Bristol, United Kingdom
CHU de Nantes - Hôtel-Dieu
🇫🇷Nantes, Pays De La Loire, France
Retinal Research Institute (retina consultants of AZ)
🇺🇸Phoenix, Arizona, United States
VitreoRetinal Associates, P.A.
🇺🇸Gainesville, Florida, United States
VitreoRetinal Surgery, PLLC
🇺🇸Minneapolis, Minnesota, United States
Casey Eye Institute
🇺🇸Portland, Oregon, United States
Austin Research Center for Retina, PLLC
🇺🇸Austin, Texas, United States
Retinal Consultants of San Antonio
🇺🇸San Antonio, Texas, United States