HORIZON: A Phase II Study to Evaluate the Safety and Efficacy of Two Doses of GT005

Dry Age-related Macular Degeneration Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04566445
• Other study ID #: GT005-03
• Secondary ID: CPPY988A12201
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 28, 2020
• Est. completion date: May 31, 2024

Study information

• Verified date: March 2024
• Source: Gyroscope Therapeutics Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 255
• Est. completion date: May 31, 2024
• Est. primary completion date: May 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Dry Age-related Macular Degeneration
• Geographic Atrophy
• Macular Degeneration

Intervention

Drug:
• GT005: Medium Dose
The study will test two doses of GT005: Medium Dose and High Dose.
• GT005: High Dose
The study will test two doses of GT005: Medium Dose and High Dose.

Locations

Country	Name	City	State
Australia	The University of Melbourne - The Centre for Eye Research Australia (CERA)	Melbourne E.	Victoria
Australia	Sydney Hospital and Sydney Eye Hospital	Sydney	New South Wales
France	CHU Dijon - Hopital Mitterrand	Dijon
France	Centre Paradis Monticelli	Marseille
France	CHU de Nantes - Hôtel-Dieu	Nantes
Germany	Universitätsklinikum Bonn	Bonn
Germany	Internationale Innovative Ophthalmochirurgie	Düsseldorf
Germany	Universitaetsklinikum Schleswig-Holstein - Campus Lübeck	Lübeck
Germany	Universitaetsklinikum Tuebingen	Tuebingen
Poland	Oftalmika Spolka z ograniczona odpowiedzialnoscia	Bydgoszcz
Spain	Instituto de microcirugía ocular	Barcelona
Spain	Clinica Baviera	Madrid
Spain	Clinica Universidad de Navarra - Pamplona	Pamplona
United Kingdom	Moorfields Eye Hospital - NHS Foundation Trust	London
United Kingdom	Retina Clinic London	London
United Kingdom	John Radcliffe Hospital	Oxford
United Kingdom	Sunderland Eye Infirmary	Sunderland
United States	Southeast Retina Center	Augusta	Georgia
United States	Austin Research Center for Retina, PLLC	Austin	Texas
United States	The Retina Care Center	Baltimore	Maryland
United States	Retina Consultants of Houston-TMC	Bellaire	Texas
United States	Retina Vitreous Associates Medical Group	Beverly Hills	California
United States	Ophthalamic Consultants of Boston (OCB)	Boston	Massachusetts
United States	Illinois Retina Associates	Chicago	Illinois
United States	Cincinnati Eye Institute	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Retina Foundation of the Southwest	Dallas	Texas
United States	Texas Retina Associates (Dallas)	Dallas	Texas
United States	Rand Eye Institute	Deerfield Beach	Florida
United States	Southwest Retina Research Center	Durango	Colorado
United States	Duke Eye Center	Durham	North Carolina
United States	Erie Retinal Surgery ,INC	Erie	Pennsylvania
United States	Oregon Retina	Eugene	Oregon
United States	Retina Consultants of Orange County	Fullerton	California
United States	VitreoRetinal Associates, P.A.	Gainesville	Florida
United States	Charles Retina Institute	Germantown	Tennessee
United States	Retina Associates of Michigan	Grand Blanc	Michigan
United States	Midwest Eye Institute Northside	Indianapolis	Indiana
United States	Southeastern Retina Associates, PC	Knoxville	Tennessee
United States	University Retina Macula Associates PC	Lemont	Illinois
United States	Georgia Retina PC	Marietta	Georgia
United States	Bascom Palmer Eye Institute	Miami	Florida
United States	Northern California Retina Vitreous Associates	Mountain View	California
United States	Columbia University Medical Center	New York	New York
United States	Byers Eye Institute at Stanford	Palo Alto	California
United States	Mid Atlantic Retina - Wills Eye Hospital	Philadelphia	Pennsylvania
United States	Retinal Research Institute (retina consultants of AZ)	Phoenix	Arizona
United States	Casey Eye Institute - OHSU	Portland	Oregon
United States	Retina Consultants of San Diego	Poway	California
United States	Sierra Eye Associates	Reno	Nevada
United States	Retina Associates of Western New York	Rochester	New York
United States	Associated Retinal Consultants PC	Royal Oak	Michigan
United States	University of California (UC) Davis Medical Group Eye Center	Sacramento	California
United States	Retina Vitreous Associates of Florida	Saint Petersburg	Florida
United States	Rocky Mountain Retina Consultants	Salt Lake City	Utah
United States	Retinal Consultants of San Antonio	San Antonio	Texas
United States	Department of Ophthalmology UW Medicine	Seattle	Washington
United States	Retina Associates, LLC	Shawnee Mission	Kansas
United States	Retina Center Northwest	Silverdale	Washington
United States	Retina Consultants of Houston	The Woodlands	Texas
United States	Palmetto Retina Center	West Columbia	South Carolina
United States	Wolfe Eye Clinic	West Des Moines	Iowa

Sponsors (2)

Lead Sponsor	Collaborator
Gyroscope Therapeutics Limited	Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  France,  Germany,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression of geographic atrophy	The change from baseline to Week 72 in GA area as measured by fundus autofluorescence (FAF)	72 weeks
Secondary	Progression of geographic atrophy	The change from baseline through Week 96 in GA area as measured by fundus autofluorescence (FAF)	96 weeks
Secondary	Evaluation of the safety and tolerability of GT005	Frequency of treatment emergent adverse events (AEs)	96 weeks
Secondary	Evaluation of the effect of GT005 on retinal anatomical measures	Change in retinal morphology on multimodal imaging	96 weeks
Secondary	Evaluation of the effect of GT005 on functional measures	Change in best corrected visual acuity (BCVA) Score via the early treatment for diabetic retinopathy (ETDRS) chart	96 weeks
Secondary	Evaluation of the effect of GT005 on functional measures	Change in low luminance difference (LLD) via the ETDRS chart	96 weeks
Secondary	Evaluation of the effect of GT005 on visual function	Change in reading performance as assessed by Minnesota low-vision reading test (MNRead) chart	96 weeks
Secondary	Evaluation of the effect of GT005 on visual function	Change in functional reading independence (FRI) index	96 weeks
Secondary	Evaluation of the effect of GT005 on patient-reported outcomes	Change in quality of life measured on the Visual Function Questionnaire-25 (VFQ-25)	96 weeks