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

NCT04437368 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: GT005-02CPPY988A122022019-003421-22
• Study Type: interventional
• Target: 98
• Locations: 8 countries
• Sites: 55

Brief Summary

The purpose of this clinical study was 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).

Conditions

Dry Age-related Macular Degeneration

Keywords

Geographic atrophy; Retinal disease; Eye disease; Retinal degeneration; Macular atrophy; Dry age-related macular degeneration

Outcome Measures

Primary Outcomes (1)

• The Change From Baseline to Week 48 in Geographic Atrophy (GA) - Part 1

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

  Baseline, Weeks 12, 24, 36, and 48

Secondary Outcomes (15)

• The Change From Baseline in Geographic Atrophy (GA) at Week 72 and Week 96 - Part 1

  Baseline, Weeks 72 and 96

• Summary of Adverse Events - Parts 1 and 2 Combined

  Adverse events are reported from randomization up to end of study, for a maximum timeframe of approximately 96 weeks.

• Ocular Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye - Parts 1 and 2 Combined

  Adverse events are reported from randomization up to end of study, for a maximum timeframe of approximately 96 weeks.

• Non-ocular Adverse Events - Summary - Parts 1 and 2 Combined

  Adverse events are reported from randomization up to end of study, for a maximum timeframe of approximately 96 weeks.

• Change in GA Morphology From Baseline to Week 96 on Colour Fundus Photography (CFP) - Number of Participants With Increase in Fundus Autofluorescence (FAF) - Part 1

  Baseline, Weeks 5,12,24,36,48,72,96

Study Arms (3)

GT005 Low dose [2E10 vg]

EXPERIMENTAL

GT005 Low dose \[2E10 vg\] (Parts 1 and 2)

Drug: GT005

GT005 High dose [2E11 vg]

EXPERIMENTAL

GT005 High dose \[2E11 vg\] (Part 1)

Drug: GT005

Untreated control

NO INTERVENTION

Untreated control (Parts 1 and 2)

Interventions

GT005 DRUG

GT005 is a recombinant, non-replicating AAV2 expressing human complement factor I (CFI). GT005 was administered as a single time subretinal injection into the study eye of subjects allocated to one of the two GT005 doses.

GT005 High dose [2E11 vg]; GT005 Low dose [2E10 vg]

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Gyroscope Therapeutics Limited: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (55)

Retinal Research Institute (retina consultants of AZ)

Phoenix, Arizona, 85053, United States

Location

Retina Associates of Southern California

Huntington Beach, California, 92647, United States

Location

Byers Eye Institute at Stanford

Palo Alto, California, 94303, United States

Location

Retina Consultants San Diego

Poway, California, 92064, United States

Location

VitreoRetinal Associates, P.A.

Gainesville, Florida, 32607, United States

Location

Bascom Palmer Eye Institute

Miami, Florida, 33136, United States

Location

Retina Vitreous Associates of Florida

St. Petersburg, Florida, 33711, United States

Location

Southeast Retina Center

Augusta, Georgia, 30909, United States

Location

University Retina Macula Associates PC

Lemont, Illinois, 60439, United States

Location

Midwest Eye Institute Northside

Indianapolis, Indiana, 46290, United States

Location

Wolfe Eye Clinic

West Des Moines, Iowa, 50266, United States

Location

The Retina Care Center

Baltimore, Maryland, 21209, United States

Location

Ophthalmic Consultants of Boston (OCB)

Boston, Massachusetts, 02114, United States

Location

VitreoRetinal Surgery, PLLC

Minneapolis, Minnesota, 55435, United States

Location

Sierra Eye Associates

Reno, Nevada, 89502, United States

Location

Vision Research Center Eye Associates of New Mexico

Albuquerque, New Mexico, 87109, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Retina Associates of Western New York

Rochester, New York, 14620, United States

Location

Cincinnati Eye Institute

Cincinnati, Ohio, 45242, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Oregon Retina

Eugene, Oregon, 97401, United States

Location

Casey Eye Institute

Portland, Oregon, 97239, United States

Location

Erie Retinal Surgery, INC

Erie, Pennsylvania, 16507, United States

Location

Mid Atlantic Retina

Philadelphia, Pennsylvania, 19107, United States

Location

Southeastern Retina Associates, PC

Knoxville, Tennessee, 37922, United States

Location

Charles Retina Institute

Memphis, Tennessee, 38138, United States

Location

Austin Research Center for Retina, PLLC

Austin, Texas, 78705, United States

Location

Retina Consultants of Houston-TMC

Bellaire, Texas, 77401, United States

Location

Texas Retina Associates

Dallas, Texas, 75231, United States

Location

Retinal Consultants of San Antonio

San Antonio, Texas, 78240, United States

Location

Department of Ophthalmology UW Medicine

Seattle, Washington, 98104-2499, United States

Location

West Virginia University

Morgantown, West Virginia, 26506, United States

Location

The University of Melbourne - The Centre for Eye Research Australia (CERA)

Melbourne E., Victoria, Australia

Location

Sydney Hospital and Sydney Eye Hospital

Sydney, 2000, Australia

Location

Centre Paradis Monticelli

Marseille, Alpes-Cote d'Azur, 13008, France

Location

CHU Hôpital F. Mitterrand

Dijon, Bourgogne-Franche-Comté, 21079, France

Location

CHU de Nantes - Hôtel-Dieu

Nantes, Pays de la Loire Region, 44000, France

Location

Universitaetsklinikum Schleswig-Holstein Campus Lübeck

Lübeck, Schleswig-Holstein, 23538, Germany

Location

Universitaetsklinikum Bonn

Bonn, 53127, Germany

Location

Internationale Innovative Ophthalmochirurgie

Düsseldorf, 40549, Germany

Location

St. Franziskus-Hospital

Münster, 48145, Germany

Location

Universitatsklinikum Tübingen

Tübingen, 72076, Germany

Location

Stichting Radboud Universitair Medisch Centrum

Nijmegen, 6525 GA, Netherlands

Location

Oftalmika Spolka z ograniczona odpowiedzialnoscia

Bydgoszcz, 85-631, Poland

Location

Hospital Universitari General de Catalunya

Sant Cugat del Vallès, Barcelona, 08195, Spain

Location

Clinica Universidad de Navarra - Pamplona

Pamplona, Navarre, 31008, Spain

Location

Hospital La Arruzafa

Córdoba, 14012, Spain

Location

Clinica Baviera

Madrid, 28046, Spain

Location

Clinica Oftalvist Valencia

Valencia, 46100, Spain

Location

Bristol Eye Hospital

Bristol, BS1 2LX, United Kingdom

Location

St.Paul's Eye Unit

Liverpool, L7 8XP, United Kingdom

Location

Moorfields Eye Hospital - NHS Foundation Trust

London, EC1V 2PD, United Kingdom

Location

The Retina Clinic London

London, W1G 7LB, United Kingdom

Location

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, S10 2SB, United Kingdom

Location

Sunderland Eye Infirmary

Sunderland, SR2 9HP, United Kingdom

Location

Related Publications (1)

• Tzoumas N, Riding G, Williams MA, Steel DH. Complement inhibitors for age-related macular degeneration. Cochrane Database Syst Rev. 2023 Jun 14;6(6):CD009300. doi: 10.1002/14651858.CD009300.pub3.

  PMID: 37314061 DERIVED

Related Links

• Novartis Clinical Trial Results

MeSH Terms

Conditions

Geographic Atrophy; Retinal Diseases; Eye Diseases; Retinal Degeneration; Anetoderma

Condition Hierarchy (Ancestors)

Macular Degeneration; Eye Diseases, Hereditary; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Abnormalities; Skin Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: June 3, 2020
• First Posted: June 18, 2020
• Study Start: April 26, 2019
• Primary Completion: April 5, 2024
• Study Completion: April 5, 2024
• Last Updated: January 27, 2026
• Results First Posted: August 12, 2025

Record last verified: 2026-01

Locations

AU (2); ES (5); NL (1); US (32); GB (6); DE (5); FR (3); PL (1)