Clinical trial NCT04566445: HORIZON: A Phase II Study to Evaluate the Safety and Efficacy of Two Doses of GT005
Official title: HORIZON: A Phase II, Open-label, Outcomes-assessor Masked, Multicentre, Randomised, Controlled 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 Dry Age-related Macular Degeneration
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Dry Age-related Macular Degeneration
Keywords: Dry age-related macular degeneration
Geographic atrophy
Retinal disease
Eye disease
Retinal degeneration
Macular atrophy
Lead sponsor: Gyroscope Therapeutics Limited
Sponsor class: INDUSTRY
Collaborators: name: Novartis Pharmaceuticals
First posted: 2020-09-28
Enrollment: 255
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 II, open-label, outcomes-assessor masked, multicentre, randomised, controlled 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, open-label, outcomes-assessor masked, multicentre, randomised, controlled 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 and a 96-week study period.

Subjects will be randomised to one of two groups; GT005 or the untreated control group.

Eligibility 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; 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 and meets inclusion criteria 3a, and a diagnosis of AMD in the contralateral eye (except if monocular)
4. GA lesion(s) within an acceptable size on FAF, 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
7. Have a BCVA of ≥24 letters (6/95 or 20/320 Snellen acuity equivalent), using ETDRS charts, in the study eye
8. a. In Stage 1: Meet one of the pre-specified AMD genetic subgroup criteria; 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 (not required for postmenopausal women) or provide documentation of being surgically sterilised

Exclusion Criteria:

1. a. In Stage 1: Carriers of excluded genetic variants; b. In Stage 2: Subjects are excluded if they have a clinical diagnosis of Stargardt Disease or other retinal dystrophies
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
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 use of two or more topical agents; or a history of glaucoma-filtering or valve surgery
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 (AREDS) formula
10. Have received a gene or cell therapy at any time.
11. Have a contraindication to the protocol specified 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

Primary outcomes:
measure: Progression of geographic atrophy
timeFrame: 72 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: Beverly Hills
country: United States
facility: Retina Vitreous Associates Medical Group
state: California
city: Fullerton
country: United States
facility: Retina Consultants of Orange County
state: California
city: Mountain View
country: United States
facility: Northern California Retina Vitreous Associates
state: California
city: Palo Alto
country: United States
facility: Byers Eye Institute at Stanford
state: California
city: Poway
country: United States
facility: Retina Consultants of San Diego
state: California
city: Sacramento
country: United States
facility: University of California (UC) Davis Medical Group Eye Center
state: California
city: Durango
country: United States
facility: Southwest Retina Research Center
state: Colorado
city: Deerfield Beach
country: United States
facility: Rand Eye Institute
state: Florida
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: Marietta
country: United States
facility: Georgia Retina PC
state: Georgia
city: Chicago
country: United States
facility: Illinois Retina Associates
state: Illinois
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: Shawnee Mission
country: United States
facility: Retina Associates, LLC
state: Kansas
city: Baltimore
country: United States
facility: The Retina Care Center
state: Maryland
city: Boston
country: United States
facility: Ophthalamic Consultants of Boston (OCB)
state: Massachusetts
city: Grand Blanc
country: United States
facility: Retina Associates of Michigan
state: Michigan
city: Royal Oak
country: United States
facility: Associated Retinal Consultants PC
state: Michigan
city: Reno
country: United States
facility: Sierra Eye Associates
state: Nevada
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: Durham
country: United States
facility: Duke Eye Center
state: North Carolina
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 - OHSU
state: Oregon
city: Erie
country: United States
facility: Erie Retinal Surgery ,INC
state: Pennsylvania
city: Philadelphia
country: United States
facility: Mid Atlantic Retina - Wills Eye Hospital
state: Pennsylvania
city: West Columbia
country: United States
facility: Palmetto Retina Center
state: South Carolina
city: Germantown
country: United States
facility: Charles Retina Institute
state: Tennessee
city: Knoxville
country: United States
facility: Southeastern Retina Associates, PC
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: Retina Foundation of the Southwest
state: Texas
city: Dallas
country: United States
facility: Texas Retina Associates (Dallas)
state: Texas
city: San Antonio
country: United States
facility: Retinal Consultants of San Antonio
state: Texas
city: The Woodlands
country: United States
facility: Retina Consultants of Houston
state: Texas
city: Salt Lake City
country: United States
facility: Rocky Mountain Retina Consultants
state: Utah
city: Seattle
country: United States
facility: Department of Ophthalmology UW Medicine
state: Washington
city: Silverdale
country: United States
facility: Retina Center Northwest
state: Washington
city: Sydney
country: Australia
facility: Sydney Hospital and Sydney Eye Hospital
state: New South Wales
city: Melbourne E.
country: Australia
facility: The University of Melbourne - The Centre for Eye Research Australia (CERA)
state: Victoria
city: Dijon
country: France
facility: CHU Dijon - Hopital Mitterrand
city: Marseille
country: France
facility: Centre Paradis Monticelli
city: Nantes
country: France
facility: CHU de Nantes - Hôtel-Dieu
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Düsseldorf
country: Germany
facility: Internationale Innovative Ophthalmochirurgie
city: Lübeck
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein - Campus Lübeck
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen
city: Bydgoszcz
country: Poland
facility: Oftalmika Spolka z ograniczona odpowiedzialnoscia
city: Barcelona
country: Spain
facility: Instituto de microcirugía ocular
city: Madrid
country: Spain
facility: Clinica Baviera
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra - Pamplona
city: London
country: United Kingdom
facility: Moorfields Eye Hospital - NHS Foundation Trust
city: London
country: United Kingdom
facility: Retina Clinic London
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
city: Sunderland
country: United Kingdom
facility: Sunderland Eye Infirmary
Study officials:
References: