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

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

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: Medium Dose; Drug: GT005: High Dose

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 255
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Gyroscope Gyroscope Therapeutics; Phone Number: +441438532142 +441438532142; Email: clinicaltrials@gyroscopetx.com

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2000
      • Sydney Hospital and Sydney Eye Hospital
  • Victoria
    • Melbourne E., Victoria, Australia, 3002
      • The University of Melbourne - The Centre for Eye Research Australia (CERA)
• France
  • Dijon, France, 21000
    • CHU Dijon - Hopital Mitterrand
  • Marseille, France, 13008
    • Centre Paradis Monticelli
  • Nantes, France, 44093
    • CHU de Nantes - Hôtel-Dieu
• Germany
  • Bonn, Germany, 53127
    • Universitatsklinikum Bonn
  • Düsseldorf, Germany, 40549
    • Internationale Innovative Ophthalmochirurgie
  • Lübeck, Germany, 23562
    • Universitaetsklinikum Schleswig-Holstein - Campus Lübeck
  • Tuebingen, Germany, 72076
    • Universitaetsklinikum Tuebingen
• Poland
  • Bydgoszcz, Poland, 85-631
    • Oftalmika Spolka z ograniczona odpowiedzialnoscia
• Spain
  • Barcelona, Spain, 08035
    • Instituto de Microcirugia Ocular
  • Madrid, Spain, 28046
    • Clinica Baviera
  • Pamplona, Spain, 31008
    • Clinica Universidad de Navarra - Pamplona
• United Kingdom
  • London, United Kingdom, W1G 7LB
    • Retina Clinic London
  • London, United Kingdom, EC1V 2PD
    • Moorfields Eye Hospital - NHS Foundation Trust
  • Oxford, United Kingdom, OX3 9DU
    • John Radcliffe Hospital
  • Sunderland, United Kingdom, SR2 9HP
    • Sunderland Eye Infirmary
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85053
      • Retinal Research Institute (retina consultants of AZ)
  • California
    • Beverly Hills, California, United States, 90211
      • Retina Vitreous Associates Medical Group
    • Fullerton, California, United States, 92835
      • Retina Consultants of Orange County
    • Mountain View, California, United States, 94040
      • Northern California Retina Vitreous Associates
    • Palo Alto, California, United States, 94303
      • Byers Eye Institute at Stanford
    • Poway, California, United States, 92064
      • Retina Consultants of San Diego
    • Sacramento, California, United States, 95817
      • University of California (UC) Davis Medical Group Eye Center
  • Colorado
    • Durango, Colorado, United States, 81303
      • Southwest Retina Research Center
  • Florida
    • Deerfield Beach, Florida, United States, 33064
      • Rand Eye Institute
    • 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
    • Marietta, Georgia, United States, 30060
      • Georgia Retina PC
  • Illinois
    • Chicago, Illinois, United States, 60657
      • Illinois Retina Associates
    • Lemont, Illinois, United States, 60452
      • 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
  • Kansas
    • Shawnee Mission, Kansas, United States, 66204
      • Retina Associates, LLC
  • Maryland
    • Baltimore, Maryland, United States, 21209
      • The Retina Care Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Ophthalamic Consultants of Boston (OCB)
  • Michigan
    • Grand Blanc, Michigan, United States, 48439
      • Retina Associates of Michigan
    • Royal Oak, Michigan, United States, 48073
      • Associated Retinal Consultants PC
  • Nevada
    • Reno, Nevada, United States, 89502
      • Sierra Eye Associates
  • 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
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke Eye Center
  • 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 - OHSU
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16507
      • Erie Retinal Surgery ,INC
    • Philadelphia, Pennsylvania, United States, 19107
      • Mid Atlantic Retina - Wills Eye Hospital
  • South Carolina
    • West Columbia, South Carolina, United States, 29169
      • Palmetto Retina Center
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Charles Retina Institute
    • Knoxville, Tennessee, United States, 37922
      • Southeastern Retina Associates, PC
  • 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
      • Retina Foundation of the Southwest
    • Dallas, Texas, United States, 75231
      • Texas Retina Associates (Dallas)
    • San Antonio, Texas, United States, 78240
      • Retinal Consultants of San Antonio
    • The Woodlands, Texas, United States, 77384
      • Retina Consultants of Houston
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Rocky Mountain Retina Consultants
  • Washington
    • Seattle, Washington, United States, 98104-2499
      • Department of Ophthalmology UW Medicine
    • Silverdale, Washington, United States, 98383
      • Retina Center Northwest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 53 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. 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GT005 Medium Dose; Approximately 83 subjects are planned, with subjects randomised to GT005 Medium Dose.	Drug: GT005: Medium Dose; The study will test two doses of GT005: Medium Dose and High Dose.
Experimental: GT005 High Dose; Approximately 83 subjects are planned, with subjects randomised to GT005 High Dose.	Drug: GT005: High Dose; The study will test two doses of GT005: Medium Dose and High Dose.
No Intervention: Untreated control; Approximately 83 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 72 in GA area as measured by fundus autofluorescence (FAF)	72 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the safety and tolerability of GT005	Frequency of treatment emergent adverse events (AEs)	96 weeks
Evaluation of the effect of GT005 on functional measures	Change in low luminance difference (LLD) via the ETDRS chart	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	96 weeks
Evaluation of the effect of GT005 on visual function	Change in functional reading independence (FRI) index	96 weeks
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 effect of GT005 on retinal anatomical measures	Change in retinal morphology on multimodal imaging	96 weeks
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
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

Collaborators and Investigators

• Sponsor: Gyroscope Therapeutics Limited
• Collaborators: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2020
• Primary Completion (Estimated): May 31, 2024
• Study Completion (Estimated): May 31, 2024

Study Registration Dates

• First Submitted: September 9, 2020
• First Submitted That Met QC Criteria: September 22, 2020
• First Posted (Actual): September 28, 2020

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 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: GT005-03; CPPY988A12201 (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