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

Primary Purpose

Dry Age-related Macular Degeneration

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
GT005; Low Dose
GT005; High Dose
GT005; Low Dose
Sponsored by
Gyroscope Therapeutics Limited
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dry Age-related Macular Degeneration focused on measuring Geographic atrophy, Retinal disease, Eye disease, Retinal degeneration, Macular atrophy, Dry age-related macular degeneration

Eligibility Criteria

55 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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
  4. GA lesion(s) within an acceptable size on FAF, 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
  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. Have a rare genetic variant of the CFI gene, defined as a minor allele frequency of <1%
  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 women who are postmenopausal or surgically sterilised)

Exclusion Criteria:

  1. Have a history, or evidence, of CNV in the study eye
  2. Presence of moderate/severe or worse non-proliferative diabetic retinopathy in the study eye
  3. Have history of vitrectomy, sub-macular surgery, or macular photocoagulation in the study eye
  4. History of intraocular surgery in the study eye within 12 weeks prior to Screening.
  5. Have clinically significant cataract that may require surgery during the study period in the study eye.
  6. Presence of moderate to severe glaucomatous optic neuropathy in the study eye, uncontrolled intraocular pressure (IOP) despite the use of more than two topical agents, or a history of glaucoma-filtering or valve surgery
  7. Axial myopia of greater than -8 diopters in the study eye
  8. 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
  9. Have a contraindication to the specified protocol corticosteroid regimen
  10. 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
  11. Have received a gene or cell therapy at any time
  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

Sites / Locations

  • Retinal Research Institute (retina consultants of AZ)
  • Retina Associates of Southern California
  • Byers Eye Institute at Stanford
  • Retina Consultants San Diego
  • VitreoRetinal Associates, P.A.
  • Bascom Palmer Eye Institute
  • Retina Vitreous Associates of Florida
  • Southeast Retina Center
  • University Retina Macula Associates PC
  • Midwest Eye Institute Northside
  • Wolfe Eye Clinic
  • The Retina Care Center
  • Ophthalmic Consultants of Boston (OCB)
  • VitreoRetinal Surgery, PLLC
  • Sierra Eye Associates
  • Vision Research Center Eye Associates of New Mexico
  • Columbia University Medical Center
  • Retina Associates of Western New York
  • Cincinnati Eye Institute
  • Cleveland Clinic
  • Oregon Retina
  • Casey Eye Institute
  • Erie Retinal Surgery, INC
  • Mid Atlantic Retina
  • Southeastern Retina Associates, PC
  • Charles Retina Institute
  • Austin Research Center for Retina, PLLC
  • Retina Consultants of Houston-TMC
  • Texas Retina Associates
  • Retinal Consultants of San Antonio
  • Department of Ophthalmology UW Medicine
  • West Virginia University
  • The University of Melbourne - The Centre for Eye Research Australia (CERA)
  • Sydney Hospital and Sydney Eye Hospital
  • Centre Paradis Monticelli
  • CHU Hôpital F. Mitterrand
  • CHU de Nantes - Hôtel-Dieu
  • Universitaetsklinikum Schleswig-Holstein Campus Lübeck
  • Universitaetsklinikum Bonn
  • Internationale Innovative Ophthalmochirurgie
  • St. Franziskus-Hospital
  • Universitatsklinikum Tübingen
  • Stichting Radboud Universitair Medisch Centrum
  • Oftalmika Spolka z ograniczona odpowiedzialnoscia
  • Hospital Universitari General de Catalunya
  • Clinica Universidad de Navarra - Pamplona
  • Hospital La Arruzafa
  • Clinica Baviera
  • Clinica Oftalvist Valencia
  • Bristol Eye Hospital
  • St.Paul's Eye Unit
  • Moorfields Eye Hospital - NHS Foundation Trust
  • The Retina Clinic London
  • Sheffield Teaching Hospitals NHS Foundation Trust
  • Sunderland Eye Infirmary

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

No Intervention

Experimental

No Intervention

Arm Label

Part 1 - GT005 Low Dose

Part 1 - GT005 High Dose

Part 1 - Untreated control

Part 2 - GT005 Low Dose

Part 2 - Untreated control

Arm Description

Approximately 25 subjects are planned, with subjects randomised to GT005 Low Dose.

Approximately 25 subjects are planned, with subjects randomised to GT005 High Dose.

Approximately 25 subjects are planned, with subjects randomised to untreated control.

Approximately 116 subjects are planned, with subjects randomised to Part 2 - GT005 Low Dose.

Approximately 54 subjects are planned, with subjects randomised to untreated control.

Outcomes

Primary Outcome Measures

Progression of geographic atrophy
The change from baseline to Week 48 in GA area as measured by fundus autofluorescence (FAF)

Secondary Outcome Measures

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

Full Information

First Posted
June 3, 2020
Last Updated
October 20, 2023
Sponsor
Gyroscope Therapeutics Limited
Collaborators
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT04437368
Brief Title
EXPLORE: A Phase II Study to Evaluate the Safety and Efficacy of Two Doses of GT005
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Terminated
Why Stopped
Terminated for interim analysis demonstrating futility (trial highly unlikely to meet efficacy outcome). The trial is not ending early because of medical problems or concerns.
Study Start Date
July 14, 2020 (Actual)
Primary Completion Date
August 24, 2023 (Actual)
Study Completion Date
August 24, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gyroscope Therapeutics Limited
Collaborators
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dry Age-related Macular Degeneration
Keywords
Geographic atrophy, Retinal disease, Eye disease, Retinal degeneration, Macular atrophy, Dry age-related macular degeneration

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
The overall objectives of the study are to evaluate the safety and efficacy (anatomical and functional visual outcomes) of two doses of GT005 in genetically defined subjects with GA due to AMD.
Allocation
Randomized
Enrollment
98 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part 1 - GT005 Low Dose
Arm Type
Experimental
Arm Description
Approximately 25 subjects are planned, with subjects randomised to GT005 Low Dose.
Arm Title
Part 1 - GT005 High Dose
Arm Type
Experimental
Arm Description
Approximately 25 subjects are planned, with subjects randomised to GT005 High Dose.
Arm Title
Part 1 - Untreated control
Arm Type
No Intervention
Arm Description
Approximately 25 subjects are planned, with subjects randomised to untreated control.
Arm Title
Part 2 - GT005 Low Dose
Arm Type
Experimental
Arm Description
Approximately 116 subjects are planned, with subjects randomised to Part 2 - GT005 Low Dose.
Arm Title
Part 2 - Untreated control
Arm Type
No Intervention
Arm Description
Approximately 54 subjects are planned, with subjects randomised to untreated control.
Intervention Type
Drug
Intervention Name(s)
GT005; Low Dose
Intervention Description
Part 1 of the study will test two doses of GT005: Low Dose and High Dose.
Intervention Type
Drug
Intervention Name(s)
GT005; High Dose
Intervention Description
Part 1 of the study will test two doses of GT005: Low Dose and High Dose.
Intervention Type
Drug
Intervention Name(s)
GT005; Low Dose
Intervention Description
Part 2 of the study will test one dose: Low Dose.
Primary Outcome Measure Information:
Title
Progression of geographic atrophy
Description
The change from baseline to Week 48 in GA area as measured by fundus autofluorescence (FAF)
Time Frame
48 weeks
Secondary Outcome Measure Information:
Title
Progression of geographic atrophy
Description
The change from baseline through Week 96 in GA area as measured by fundus autofluorescence (FAF)
Time Frame
96 weeks
Title
Evaluation of the safety and tolerability of GT005
Description
Frequency of treatment emergent adverse events (AEs) through Week 96
Time Frame
96 weeks
Title
Evaluation of the effect of GT005 on retinal anatomical measures
Description
Change in retinal morphology on multimodal imaging through Week 96
Time Frame
96 weeks
Title
Evaluation of the effect of GT005 on functional measures
Description
Change in BCVA Score via the early treatment for diabetic retinopathy (ETDRS) chart through Week 96
Time Frame
96 weeks
Title
Evaluation of the effect of GT005 on functional measures
Description
Change in low luminance difference (LLD) via the ETDRS chart through Week 96
Time Frame
96 weeks
Title
Evaluation of the effect of GT005 on visual function
Description
Change in reading performance as assessed by Minnesota low-vision reading test (MNRead) Chart through Week 96
Time Frame
96 weeks
Title
Evaluation of the effect of GT005 on visual function
Description
Change in functional reading independence (FRI) index through Week 96
Time Frame
96 weeks
Title
Evaluation of the effect of GT005 on patient-reported outcomes
Description
Change in quality of life measured on the Visual Functioning Questionnaire-25 (VFQ-25) through Week 96
Time Frame
96 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Able and willing to give written informed consent Age ≥55 years 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) Have GA lesion(s) total size between or equal to 1.25mm2 to 17.5mm2 in the study eye The GA lesion(s) in the study eye must reside completely within the FAF image Up to 25% of the enrolled study population are permitted to have CNV in the fellow eye, defined as either: Non-exudative/sub-clinical fellow eye CNV identified at Screening, or Known history of fellow eye CNV with either ≥2 years since diagnosis or with no active treatment required in 6 months prior to Screening Have a BCVA of 24 letters (6/95 and 20/320 Snellen acuity equivalent) or better, using ETDRS charts, in the study eye 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 Able to attend all study visits and complete the study procedures 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: Subjects who have a clinical diagnosis of Stargardt Disease or other retinal dystrophies, confirmed by the central reading centre Have a history, or evidence, of CNV in the study eye Presence of moderate/severe or worse non-proliferative diabetic retinopathy in the study eye Have history of vitrectomy, sub-macular surgery, or macular photocoagulation in the study eye 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 Have clinically significant cataract that may require surgery during the study period in the study eye 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 Axial myopia of greater than -8 dioptres in the study eye 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 Have a contraindication to specified protocol corticosteroid regimen 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 Have received a gene or cell therapy at any time Are unwilling to use two forms of contraception (one of which being a barrier method) for 90 days post-dosing, if relevant 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
Facility Information:
Facility Name
Retinal Research Institute (retina consultants of AZ)
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85053
Country
United States
Facility Name
Retina Associates of Southern California
City
Huntington Beach
State/Province
California
ZIP/Postal Code
92647
Country
United States
Facility Name
Byers Eye Institute at Stanford
City
Palo Alto
State/Province
California
ZIP/Postal Code
94303
Country
United States
Facility Name
Retina Consultants San Diego
City
Poway
State/Province
California
ZIP/Postal Code
92064
Country
United States
Facility Name
VitreoRetinal Associates, P.A.
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32607
Country
United States
Facility Name
Bascom Palmer Eye Institute
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Retina Vitreous Associates of Florida
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33711
Country
United States
Facility Name
Southeast Retina Center
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30909
Country
United States
Facility Name
University Retina Macula Associates PC
City
Lemont
State/Province
Illinois
ZIP/Postal Code
60439
Country
United States
Facility Name
Midwest Eye Institute Northside
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46290
Country
United States
Facility Name
Wolfe Eye Clinic
City
West Des Moines
State/Province
Iowa
ZIP/Postal Code
50266
Country
United States
Facility Name
The Retina Care Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21209
Country
United States
Facility Name
Ophthalmic Consultants of Boston (OCB)
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
VitreoRetinal Surgery, PLLC
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55435
Country
United States
Facility Name
Sierra Eye Associates
City
Reno
State/Province
Nevada
ZIP/Postal Code
89502
Country
United States
Facility Name
Vision Research Center Eye Associates of New Mexico
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87109
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Retina Associates of Western New York
City
Rochester
State/Province
New York
ZIP/Postal Code
14620
Country
United States
Facility Name
Cincinnati Eye Institute
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45242
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Oregon Retina
City
Eugene
State/Province
Oregon
ZIP/Postal Code
97401
Country
United States
Facility Name
Casey Eye Institute
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Erie Retinal Surgery, INC
City
Erie
State/Province
Pennsylvania
ZIP/Postal Code
16507
Country
United States
Facility Name
Mid Atlantic Retina
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Southeastern Retina Associates, PC
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37922
Country
United States
Facility Name
Charles Retina Institute
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38138
Country
United States
Facility Name
Austin Research Center for Retina, PLLC
City
Austin
State/Province
Texas
ZIP/Postal Code
78705
Country
United States
Facility Name
Retina Consultants of Houston-TMC
City
Bellaire
State/Province
Texas
ZIP/Postal Code
77401
Country
United States
Facility Name
Texas Retina Associates
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
Retinal Consultants of San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78240
Country
United States
Facility Name
Department of Ophthalmology UW Medicine
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104-2499
Country
United States
Facility Name
West Virginia University
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506
Country
United States
Facility Name
The University of Melbourne - The Centre for Eye Research Australia (CERA)
City
Melbourne E.
State/Province
Victoria
Country
Australia
Facility Name
Sydney Hospital and Sydney Eye Hospital
City
Sydney
ZIP/Postal Code
2000
Country
Australia
Facility Name
Centre Paradis Monticelli
City
Marseille
State/Province
Alpes-Cote d'Azur
ZIP/Postal Code
13008
Country
France
Facility Name
CHU Hôpital F. Mitterrand
City
Dijon
State/Province
Bourgogne-Franche-Comté
ZIP/Postal Code
21079
Country
France
Facility Name
CHU de Nantes - Hôtel-Dieu
City
Nantes
State/Province
Pays De La Loire
ZIP/Postal Code
44000
Country
France
Facility Name
Universitaetsklinikum Schleswig-Holstein Campus Lübeck
City
Lübeck
State/Province
Schleswig-Holstein
ZIP/Postal Code
23538
Country
Germany
Facility Name
Universitaetsklinikum Bonn
City
Bonn
ZIP/Postal Code
53127
Country
Germany
Facility Name
Internationale Innovative Ophthalmochirurgie
City
Düsseldorf
ZIP/Postal Code
40549
Country
Germany
Facility Name
St. Franziskus-Hospital
City
Münster
ZIP/Postal Code
48145
Country
Germany
Facility Name
Universitatsklinikum Tübingen
City
Tübingen
ZIP/Postal Code
72076
Country
Germany
Facility Name
Stichting Radboud Universitair Medisch Centrum
City
Nijmegen
ZIP/Postal Code
6525 GA
Country
Netherlands
Facility Name
Oftalmika Spolka z ograniczona odpowiedzialnoscia
City
Bydgoszcz
ZIP/Postal Code
85-631
Country
Poland
Facility Name
Hospital Universitari General de Catalunya
City
Sant Cugat Del Vallès
State/Province
Barcelona
ZIP/Postal Code
08195
Country
Spain
Facility Name
Clinica Universidad de Navarra - Pamplona
City
Pamplona
State/Province
Navarra
ZIP/Postal Code
31008
Country
Spain
Facility Name
Hospital La Arruzafa
City
Córdoba
ZIP/Postal Code
14012
Country
Spain
Facility Name
Clinica Baviera
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Clinica Oftalvist Valencia
City
Valencia
ZIP/Postal Code
46100
Country
Spain
Facility Name
Bristol Eye Hospital
City
Bristol
ZIP/Postal Code
BS1 2LX
Country
United Kingdom
Facility Name
St.Paul's Eye Unit
City
Liverpool
ZIP/Postal Code
L7 8XP
Country
United Kingdom
Facility Name
Moorfields Eye Hospital - NHS Foundation Trust
City
London
ZIP/Postal Code
EC1V 2PD
Country
United Kingdom
Facility Name
The Retina Clinic London
City
London
ZIP/Postal Code
W1G 7LB
Country
United Kingdom
Facility Name
Sheffield Teaching Hospitals NHS Foundation Trust
City
Sheffield
ZIP/Postal Code
S10 2SB
Country
United Kingdom
Facility Name
Sunderland Eye Infirmary
City
Sunderland
ZIP/Postal Code
SR2 9HP
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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

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