Clinical trial NCT04437368: EXPLORE: A Phase II Study to Evaluate the Safety and Efficacy of Two Doses of GT005
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Dry Age-related Macular Degeneration
Keywords: Geographic atrophy
Retinal disease
Eye disease
Retinal degeneration
Macular atrophy
Dry age-related macular degeneration
Lead sponsor: Gyroscope Therapeutics Limited
Sponsor class: INDUSTRY
Collaborators: name: Novartis Pharmaceuticals
First posted: 2020-06-18
Enrollment: 98
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.

Eligibility 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(s) 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:

   1. Non-exudative/sub-clinical fellow eye CNV identified at Screening, or
   2. 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 and 20/320 Snellen acuity equivalent) or better, using ETDRS charts, in the study eye
8. 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
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. 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:

1. Subjects who have a clinical diagnosis of Stargardt Disease or other retinal dystrophies, 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 Screening (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 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
8. Axial myopia of greater than -8 dioptres in the study eye
9. 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
10. Have a contraindication to specified protocol corticosteroid regimen
11. 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
12. Have received a gene or cell therapy at any time
13. Are unwilling to use two forms of contraception (one of which being a barrier method) for 90 days post-dosing, if relevant
14. 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

Primary outcomes:
measure: Progression of geographic atrophy
timeFrame: 48 weeks
Secondary outcomes:
measure: Progression of geographic atrophy
timeFrame: 96 weeks
measure: Evaluation of the safety and tolerability of GT005
timeFrame: 96 weeks
measure: Evaluation of the effect of GT005 on retinal anatomical measures
timeFrame: 96 weeks
measure: Evaluation of the effect of GT005 on functional measures
timeFrame: 96 weeks
measure: Evaluation of the effect of GT005 on functional measures
timeFrame: 96 weeks
measure: Evaluation of the effect of GT005 on visual function
timeFrame: 96 weeks
measure: Evaluation of the effect of GT005 on visual function
timeFrame: 96 weeks
measure: Evaluation of the effect of GT005 on patient-reported outcomes
timeFrame: 96 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Retinal Research Institute (retina consultants of AZ)
state: Arizona
city: Huntington Beach
country: United States
facility: Retina Associates of Southern California
state: California
city: Palo Alto
country: United States
facility: Byers Eye Institute at Stanford
state: California
city: Poway
country: United States
facility: Retina Consultants San Diego
state: California
city: Gainesville
country: United States
facility: VitreoRetinal Associates, P.A.
state: Florida
city: Miami
country: United States
facility: Bascom Palmer Eye Institute
state: Florida
city: Saint Petersburg
country: United States
facility: Retina Vitreous Associates of Florida
state: Florida
city: Augusta
country: United States
facility: Southeast Retina Center
state: Georgia
city: Lemont
country: United States
facility: University Retina Macula Associates PC
state: Illinois
city: Indianapolis
country: United States
facility: Midwest Eye Institute Northside
state: Indiana
city: West Des Moines
country: United States
facility: Wolfe Eye Clinic
state: Iowa
city: Baltimore
country: United States
facility: The Retina Care Center
state: Maryland
city: Boston
country: United States
facility: Ophthalmic Consultants of Boston (OCB)
state: Massachusetts
city: Minneapolis
country: United States
facility: VitreoRetinal Surgery, PLLC
state: Minnesota
city: Reno
country: United States
facility: Sierra Eye Associates
state: Nevada
city: Albuquerque
country: United States
facility: Vision Research Center Eye Associates of New Mexico
state: New Mexico
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: Retina Associates of Western New York
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Eye Institute
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Eugene
country: United States
facility: Oregon Retina
state: Oregon
city: Portland
country: United States
facility: Casey Eye Institute
state: Oregon
city: Erie
country: United States
facility: Erie Retinal Surgery, INC
state: Pennsylvania
city: Philadelphia
country: United States
facility: Mid Atlantic Retina
state: Pennsylvania
city: Knoxville
country: United States
facility: Southeastern Retina Associates, PC
state: Tennessee
city: Memphis
country: United States
facility: Charles Retina Institute
state: Tennessee
city: Austin
country: United States
facility: Austin Research Center for Retina, PLLC
state: Texas
city: Bellaire
country: United States
facility: Retina Consultants of Houston-TMC
state: Texas
city: Dallas
country: United States
facility: Texas Retina Associates
state: Texas
city: San Antonio
country: United States
facility: Retinal Consultants of San Antonio
state: Texas
city: Seattle
country: United States
facility: Department of Ophthalmology UW Medicine
state: Washington
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: Melbourne E.
country: Australia
facility: The University of Melbourne - The Centre for Eye Research Australia (CERA)
state: Victoria
city: Sydney
country: Australia
facility: Sydney Hospital and Sydney Eye Hospital
city: Marseille
country: France
facility: Centre Paradis Monticelli
state: Alpes-Cote d'Azur
city: Dijon
country: France
facility: CHU Hôpital F. Mitterrand
state: Bourgogne-Franche-Comté
city: Nantes
country: France
facility: CHU de Nantes - Hôtel-Dieu
state: Pays De La Loire
city: Lübeck
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein Campus Lübeck
state: Schleswig-Holstein
city: Bonn
country: Germany
facility: Universitaetsklinikum Bonn
city: Düsseldorf
country: Germany
facility: Internationale Innovative Ophthalmochirurgie
city: Münster
country: Germany
facility: St. Franziskus-Hospital
city: Tübingen
country: Germany
facility: Universitatsklinikum Tübingen
city: Nijmegen
country: Netherlands
facility: Stichting Radboud Universitair Medisch Centrum
city: Bydgoszcz
country: Poland
facility: Oftalmika Spolka z ograniczona odpowiedzialnoscia
city: Sant Cugat Del Vallès
country: Spain
facility: Hospital Universitari General de Catalunya
state: Barcelona
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra - Pamplona
state: Navarra
city: Córdoba
country: Spain
facility: Hospital La Arruzafa
city: Madrid
country: Spain
facility: Clinica Baviera
city: Valencia
country: Spain
facility: Clinica Oftalvist Valencia
city: Bristol
country: United Kingdom
facility: Bristol Eye Hospital
city: Liverpool
country: United Kingdom
facility: St.Paul's Eye Unit
city: London
country: United Kingdom
facility: Moorfields Eye Hospital - NHS Foundation Trust
city: London
country: United Kingdom
facility: The Retina Clinic London
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust
city: Sunderland
country: United Kingdom
facility: Sunderland Eye Infirmary
Study officials:
References: