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

Dry Age-related Macular Degeneration Clinical Trial

— EXPLORE  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04437368
• Other study ID #: GT005-02
• Secondary ID: CPPY988A12202
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 14, 2020
• Est. completion date: March 29, 2024

Study information

• Verified date: February 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, 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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 98
• Est. completion date: March 29, 2024
• Est. primary completion date: March 29, 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. 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

Related Conditions & MeSH terms

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

Intervention

Drug:
• GT005; Low Dose
Part 1 of the study will test two doses of GT005: Low Dose and High Dose.
• GT005; High Dose
Part 1 of the study will test two doses of GT005: Low Dose and High Dose.
• GT005; Low Dose
Part 2 of the study will test one dose: Low 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
France	CHU Hôpital F. Mitterrand	Dijon	Bourgogne-Franche-Comté
France	Centre Paradis Monticelli	Marseille	Alpes-Cote d'Azur
France	CHU de Nantes - Hôtel-Dieu	Nantes	Pays De La Loire
Germany	Universitaetsklinikum Bonn	Bonn
Germany	Internationale Innovative Ophthalmochirurgie	Düsseldorf
Germany	Universitaetsklinikum Schleswig-Holstein Campus Lübeck	Lübeck	Schleswig-Holstein
Germany	St. Franziskus-Hospital	Münster
Germany	Universitatsklinikum Tübingen	Tübingen
Netherlands	Stichting Radboud Universitair Medisch Centrum	Nijmegen
Poland	Oftalmika Spolka z ograniczona odpowiedzialnoscia	Bydgoszcz
Spain	Hospital La Arruzafa	Córdoba
Spain	Clinica Baviera	Madrid
Spain	Clinica Universidad de Navarra - Pamplona	Pamplona	Navarra
Spain	Hospital Universitari General de Catalunya	Sant Cugat Del Vallès	Barcelona
Spain	Clinica Oftalvist Valencia	Valencia
United Kingdom	Bristol Eye Hospital	Bristol
United Kingdom	St.Paul's Eye Unit	Liverpool
United Kingdom	Moorfields Eye Hospital - NHS Foundation Trust	London
United Kingdom	The Retina Clinic London	London
United Kingdom	Sheffield Teaching Hospitals NHS Foundation Trust	Sheffield
United Kingdom	Sunderland Eye Infirmary	Sunderland
United States	Vision Research Center Eye Associates of New Mexico	Albuquerque	New Mexico
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	Ophthalmic Consultants of Boston (OCB)	Boston	Massachusetts
United States	Cincinnati Eye Institute	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Texas Retina Associates	Dallas	Texas
United States	Erie Retinal Surgery, INC	Erie	Pennsylvania
United States	Oregon Retina	Eugene	Oregon
United States	VitreoRetinal Associates, P.A.	Gainesville	Florida
United States	Retina Associates of Southern California	Huntington Beach	California
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	Charles Retina Institute	Memphis	Tennessee
United States	Bascom Palmer Eye Institute	Miami	Florida
United States	VitreoRetinal Surgery, PLLC	Minneapolis	Minnesota
United States	West Virginia University	Morgantown	West Virginia
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	Philadelphia	Pennsylvania
United States	Retinal Research Institute (retina consultants of AZ)	Phoenix	Arizona
United States	Casey Eye Institute	Portland	Oregon
United States	Retina Consultants San Diego	Poway	California
United States	Sierra Eye Associates	Reno	Nevada
United States	Retina Associates of Western New York	Rochester	New York
United States	Retina Vitreous Associates of Florida	Saint Petersburg	Florida
United States	Retinal Consultants of San Antonio	San Antonio	Texas
United States	Department of Ophthalmology UW Medicine	Seattle	Washington
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,  Netherlands,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression of geographic atrophy	The change from baseline to Week 48 in GA area as measured by fundus autofluorescence (FAF)	48 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) through Week 96	96 weeks
Secondary	Evaluation of the effect of GT005 on retinal anatomical measures	Change in retinal morphology on multimodal imaging through Week 96	96 weeks
Secondary	Evaluation of the effect of GT005 on functional measures	Change in BCVA Score via the early treatment for diabetic retinopathy (ETDRS) chart through Week 96	96 weeks
Secondary	Evaluation of the effect of GT005 on functional measures	Change in low luminance difference (LLD) via the ETDRS chart through Week 96	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 through Week 96	96 weeks
Secondary	Evaluation of the effect of GT005 on visual function	Change in functional reading independence (FRI) index through Week 96	96 weeks
Secondary	Evaluation of the effect of GT005 on patient-reported outcomes	Change in quality of life measured on the Visual Functioning Questionnaire-25 (VFQ-25) through Week 96	96 weeks