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

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Dry Age-related Macular Degeneration
• Intervention / Treatment: Drug: GT005; Low Dose; Drug: GT005; Low Dose; Drug: GT005; High Dose

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.

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Sydney, Australia, 2000
    • Sydney Hospital and Sydney Eye Hospital
  • Victoria
    • Melbourne E., Victoria, Australia
      • The University of Melbourne - The Centre for Eye Research Australia (CERA)
• France
  • Alpes-Cote d'Azur
    • Marseille, Alpes-Cote d'Azur, France, 13008
      • Centre Paradis Monticelli
  • Bourgogne-Franche-Comté
    • Dijon, Bourgogne-Franche-Comté, France, 21079
      • CHU Hôpital F. Mitterrand
  • Pays De La Loire
    • Nantes, Pays De La Loire, France, 44000
      • CHU de Nantes - Hôtel-Dieu
• Germany
  • Bonn, Germany, 53127
    • Universitaetsklinikum Bonn
  • Düsseldorf, Germany, 40549
    • Internationale Innovative Ophthalmochirurgie
  • Münster, Germany, 48145
    • St. Franziskus-Hospital
  • Tübingen, Germany, 72076
    • Universitätsklinikum Tübingen
  • Schleswig-Holstein
    • Lübeck, Schleswig-Holstein, Germany, 23538
      • Universitaetsklinikum Schleswig-Holstein Campus Lübeck
• Netherlands
  • Nijmegen, Netherlands, 6525 GA
    • Stichting Radboud Universitair Medisch Centrum
• Poland
  • Bydgoszcz, Poland, 85-631
    • Oftalmika Spolka z ograniczona odpowiedzialnoscia
• Spain
  • Córdoba, Spain, 14012
    • Hospital La Arruzafa
  • Madrid, Spain, 28046
    • Clinica Baviera
  • Valencia, Spain, 46100
    • Clinica Oftalvist Valencia
  • Barcelona
    • Sant Cugat Del Vallès, Barcelona, Spain, 08195
      • Hospital Universitari General de Catalunya
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universidad de Navarra - Pamplona
• United Kingdom
  • Bristol, United Kingdom, BS1 2LX
    • Bristol Eye Hospital
  • Liverpool, United Kingdom, L7 8XP
    • St.Paul's Eye Unit
  • London, United Kingdom, EC1V 2PD
    • Moorfields Eye Hospital - NHS Foundation Trust
  • London, United Kingdom, W1G 7LB
    • The Retina Clinic London
  • Sheffield, United Kingdom, S10 2SB
    • Sheffield Teaching Hospitals NHS Foundation Trust
  • Sunderland, United Kingdom, SR2 9HP
    • Sunderland Eye Infirmary
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85053
      • Retinal Research Institute (retina consultants of AZ)
  • California
    • Huntington Beach, California, United States, 92647
      • Retina Associates of Southern California
    • Palo Alto, California, United States, 94303
      • Byers Eye Institute at Stanford
    • Poway, California, United States, 92064
      • Retina Consultants San Diego
  • Florida
    • Gainesville, Florida, United States, 32607
      • VitreoRetinal Associates, P.A.
    • Miami, Florida, United States, 33136
      • Bascom Palmer Eye Institute
    • Saint Petersburg, Florida, United States, 33711
      • Retina Vitreous Associates of Florida
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Southeast Retina Center
  • Illinois
    • Lemont, Illinois, United States, 60439
      • University Retina Macula Associates PC
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • Midwest Eye Institute Northside
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Wolfe Eye Clinic
  • Maryland
    • Baltimore, Maryland, United States, 21209
      • The Retina Care Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Ophthalmic Consultants of Boston (OCB)
  • Minnesota
    • Minneapolis, Minnesota, United States, 55435
      • VitreoRetinal Surgery, PLLC
  • Nevada
    • Reno, Nevada, United States, 89502
      • Sierra Eye Associates
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Vision Research Center Eye Associates of New Mexico
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • Rochester, New York, United States, 14620
      • Retina Associates of Western New York
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Cincinnati Eye Institute
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Oregon Retina
    • Portland, Oregon, United States, 97239
      • Casey Eye Institute
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16507
      • Erie Retinal Surgery, Inc
    • Philadelphia, Pennsylvania, United States, 19107
      • Mid Atlantic Retina
  • Tennessee
    • Knoxville, Tennessee, United States, 37922
      • Southeastern Retina Associates, PC
    • Memphis, Tennessee, United States, 38138
      • Charles Retina Institute
  • Texas
    • Austin, Texas, United States, 78705
      • Austin Research Center for Retina, PLLC
    • Bellaire, Texas, United States, 77401
      • Retina Consultants of Houston-TMC
    • Dallas, Texas, United States, 75231
      • Texas Retina Associates
    • San Antonio, Texas, United States, 78240
      • Retinal Consultants of San Antonio
  • Washington
    • Seattle, Washington, United States, 98104-2499
      • Department of Ophthalmology UW Medicine
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 - GT005 Low Dose; Approximately 25 subjects are planned, with subjects randomised to GT005 Low Dose.	Drug: GT005; Low Dose; Part 1 of the study will test two doses of GT005: Low Dose and High Dose.; Drug: GT005; Low Dose; Part 2 of the study will test one dose: Low Dose.
Experimental: Part 1 - GT005 High Dose; Approximately 25 subjects are planned, with subjects randomised to GT005 High Dose.	Drug: GT005; High Dose; Part 1 of the study will test two doses of GT005: Low Dose and High Dose.
No Intervention: Part 1 - Untreated control; Approximately 25 subjects are planned, with subjects randomised to untreated control.
Experimental: Part 2 - GT005 Low Dose; Approximately 116 subjects are planned, with subjects randomised to Part 2 - GT005 Low Dose.	Drug: GT005; Low Dose; Part 1 of the study will test two doses of GT005: Low Dose and High Dose.; Drug: GT005; Low Dose; Part 2 of the study will test one dose: Low Dose.
No Intervention: Part 2 - Untreated control; Approximately 54 subjects are planned, with subjects randomised to untreated control.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression of geographic atrophy	The change from baseline to Week 48 in GA area as measured by fundus autofluorescence (FAF)	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression of geographic atrophy	The change from baseline through Week 96 in GA area as measured by fundus autofluorescence (FAF)	96 weeks
Evaluation of the safety and tolerability of GT005	Frequency of treatment emergent adverse events (AEs) through Week 96	96 weeks
Evaluation of the effect of GT005 on retinal anatomical measures	Change in retinal morphology on multimodal imaging through Week 96	96 weeks
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
Evaluation of the effect of GT005 on functional measures	Change in low luminance difference (LLD) via the ETDRS chart through Week 96	96 weeks
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
Evaluation of the effect of GT005 on visual function	Change in functional reading independence (FRI) index through Week 96	96 weeks
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

Collaborators and Investigators

• Sponsor: Gyroscope Therapeutics Limited
• Collaborators: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): July 14, 2020
• Primary Completion (Estimated): March 29, 2024
• Study Completion (Estimated): March 29, 2024

Study Registration Dates

• First Submitted: June 3, 2020
• First Submitted That Met QC Criteria: June 17, 2020
• First Posted (Actual): June 18, 2020

Study Record Updates

• Last Update Posted (Estimated): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 22, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Retinal disease; Eye disease; Retinal degeneration; Macular atrophy; Dry age-related macular degeneration; Geographic atrophy
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Geographic Atrophy
• Other Study ID Numbers: GT005-02; CPPY988A12202 (Other Identifier: Novartis)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No