FOCUS: A Phase I/II First in Human Study to Evaluate the Safety and Efficacy of GT005 Administered in Subjects With Dry AMD

FOCUS: An Open Label First in Human Phase I/II Multicentre Study to Evaluate the Safety, Dose Response and Efficacy of GT005 Administered as a Single Subretinal Injection in Subjects With Macular Atrophy Due to AMD

This is an open label first in human Phase I/II multicentre study of GT005 in subjects with Macular Atrophy due to AMD

Study Overview

• Status: Active, not recruiting
• Conditions: Eye Diseases; Macular Degeneration; Retinal Degeneration; Geographic Atrophy; Dry Age-related Macular Degeneration; Retinal Disease; Macular Atrophy
• Intervention / Treatment: Biological: GT005; Device: GT005/ Device: Orbit™ Subretinal Delivery System

Detailed Description

This study will evaluate the safety, the dose response and efficacy (anatomical and functional visual outcomes) of three doses of GT005 administered as a single subretinal injection in genetically defined subjects with Macular Atrophy due to Age-related Macular Degeneration (AMD). Following consent, subjects will undergo a number of ophthalmic and clinical assessments to determine eligibility for inclusion in the study. Once eligibility is confirmed, subjects will be enrolled, receive treatment, and will be followed for 48 weeks, with the option to be followed for a further 4 years in long-term follow up after completing week 48.

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): 56
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Bristol, United Kingdom
    • Bristol Eye Hospital
  • London, United Kingdom
    • Moorfields Eye Hospital
  • London, United Kingdom, W1G 7LA
    • Retina Clinic London
  • Manchester, United Kingdom
    • Manchester Eye Hospital
  • Oxford, United Kingdom
    • Oxford University Hospital
  • Sunderland, United Kingdom
    • Sunderland Eye Infirmary
• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • Midwest Eye Institute
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Wolfe Eye Clinic
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Ophthalamic Consultants of Boston (OCB)
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • Pepose Vision Institute
  • Nevada
    • Reno, Nevada, United States, 89502
      • Sierra Eye Associates
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Cincinnati Eye Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Mid-Atlantic Retina

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 consent to study participation
2. 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)

3. Cohorts 1 to 6: GA lesion(s) total size in the study eye must be ≥1.25mm2 and ≤17.5mm2.

   Cohort 7: GA lesion(s) total size in the study eye must be ≥1.25mm2

4. GA lesion(s) in the study eye must reside completely within the FAF fundus image
5. Cohorts 1 to 3: BCVA of ≤50 letters (6/36 Snellen acuity equivalent or worse) using ETDRS charts in the study eye Cohorts 4 to 7: BCVA of ≥24 letters (6/95 and 20/320 Snellen acuity equivalent or better) using ETDRS charts in the study eye
6. Aged ≥55 years
7. Able to attend all study visits and complete the study procedures
8. Women of child-bearing potential need to have a negative urine pregnancy test within two weeks prior to receiving the drug. 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. Have evidence or history of Choroidal Neovascularisation (CNV) in the study eye. Subjects 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
2. Presence of moderate/severe non-proliferative diabetic retinopathy or worse 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 (Visit 1). Yttrium aluminum garnet capsulotomy is permitted if performed >10 weeks prior to Visit 1
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 IOP despite the use of more than two topical agents; a history of glaucoma-filtering or valve surgery is also excluded
7. Axial myopia of greater than -8 diopters in the study eye
8. 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
9. Have received a gene or cell therapy at any time
10. Have a contraindication to the specified protocol corticosteroid regimen
11. Are unwilling to use two forms of contraception (one of which being a barrier method) for 90 days post-dosing, if relevant
12. 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
13. 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
14. Cohorts 5 to 7 only: presence of metallic objects or implanted stimulator devices in or near the head, including cochlear implants, deep brain stimulators, vagus nerve stimulators, and other implanted electrodes or stimulators

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GT005 Dose 1; A single dose of GT005 will be administered via subretinal injection	Biological: GT005; A recombinant non-replicating Adeno-Associated Viral (AAV) vector encoding a human complement factor
Experimental: GT005 Dose 2; A single dose of GT005 will be administered via subretinal injection	Biological: GT005; A recombinant non-replicating Adeno-Associated Viral (AAV) vector encoding a human complement factor
Experimental: GT005 Dose 3; A single dose of GT005 will be administered via subretinal injection	Biological: GT005; A recombinant non-replicating Adeno-Associated Viral (AAV) vector encoding a human complement factor
Experimental: GT005 Dose 1, 2 or 3; A single dose of GT005 will be administered via subretinal injection. This dose will be determined by dose levels determined to be tolerable in Arms 1,2 and 3	Biological: GT005; A recombinant non-replicating Adeno-Associated Viral (AAV) vector encoding a human complement factor
Experimental: GT005 Dose 2 with Orbit Subretinal Delivery System; A single dose of GT005 will be administered with subretinal injection via suprachoroidal cannulation approach	Device: GT005/ Device: Orbit™ Subretinal Delivery System; A recombinant non-replicating Adeno-Associated Viral (AAV) vector encoding a human complement factor Device: Orbit™ Subretinal Delivery System
Experimental: GT005 Dose 3 with Orbit Subretinal Delivery System; A single dose of GT005 will be administered with subretinal injection via suprachoroidal cannulation approach	Device: GT005/ Device: Orbit™ Subretinal Delivery System; A recombinant non-replicating Adeno-Associated Viral (AAV) vector encoding a human complement factor Device: Orbit™ Subretinal Delivery System
Experimental: GT005 Dose 3 with Orbit Subretinal Delivery Sysem; A single dose of GT005 will be administered with subretinal injection via suprachoroidal cannulation approach	Device: GT005/ Device: Orbit™ Subretinal Delivery System; A recombinant non-replicating Adeno-Associated Viral (AAV) vector encoding a human complement factor Device: Orbit™ Subretinal Delivery System

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of ocular and non-ocular Treatment Emergent AEs (TEAEs) and Treatment-Emergent Serious AEs (TESAEs) Severe Adverse Events (TEAE/TESAE)	Proportion of patients with TEAEs/TESAEs after subretinal injection of GT005	240 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of successful delivery of Balanced Salt Solution (BSS) or BSS PLUS to the subretinal space (US only)	Proportion of subjects with successful delivery of BSS or BSS PLUS to subretinal space	Day 1
Rate of successful delivery of GT005 to the subretinal space (US only)	Proportion of subjects with successful delivery of GT005 to subretinal space	Day 1
Incidence of device-related AEs and SAEs (US only)	Proportion of subjects with device related AEs and SAEs after subretinal delivery with Orbit SDS	Day 1
Long-term safety of GT005 at 3 doses	Incidence of ocular and non-ocular treatment-emergent AEs (TEAEs) and treatment-emergent serious AEs (TESAEs) up to 240 weeks	240 weeks
Visual Acuity	Change from baseline in BCVA (Best Corrected Visual Acuity) and LLVA (Low Luminance Visual Acuity) score via ETDRS (Early Treatment Diabetic Retinopathy Study) chart	240 weeks
Macular Sensitivity	Change from baseline in macular sensitivity as assessed by mesopic Microperimetry	240 weeks
Geographic Atrophy	Change from baseline in GA size as assessed by fundus autofluorescence	240 weeks

Collaborators and Investigators

• Sponsor: Gyroscope Therapeutics Limited
• Collaborators: Novartis Pharmaceuticals
• Investigators: Study Director: Chief Medical Officer, Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Dreismann AK, McClements ME, Barnard AR, Orhan E, Hughes JP, Lachmann PJ, MacLaren RE. Functional expression of complement factor I following AAV-mediated gene delivery in the retina of mice and human cells. Gene Ther. 2021 May;28(5):265-276. doi: 10.1038/s41434-021-00239-9. Epub 2021 Mar 10.

Study record dates

Study Major Dates

• Study Start (Actual): December 17, 2018
• Primary Completion (Estimated): June 28, 2024
• Study Completion (Estimated): June 28, 2024

Study Registration Dates

• First Submitted: February 13, 2019
• First Submitted That Met QC Criteria: February 15, 2019
• First Posted (Actual): February 19, 2019

Study Record Updates

• Last Update Posted (Estimated): January 25, 2024
• Last Update Submitted That Met QC Criteria: January 24, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: AMD; Dry AMD; Dry Age-related Macular Degeneration (Dry AMD); Atrophic AMD; Geographic Atrophy (GA); Dry-AMD
• Additional Relevant MeSH Terms: Skin Diseases; Connective Tissue Diseases; Pathological Conditions, Anatomical; Eye Diseases, Hereditary; Skin Abnormalities; Macular Degeneration; Retinal Diseases; Geographic Atrophy; Eye Diseases; Atrophy; Retinal Degeneration; Anetoderma
• Other Study ID Numbers: GT005-01; CPPY988A12101 (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: Yes
• product manufactured in and exported from the U.S.: No