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

NCT ID: NCT03846193

Last Updated: 2026-01-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-17
• Study Completion Date: 2024-06-25

Brief Summary

This was an open label first in human Phase I/II multicentre study of GT005 in subjects with Macular Atrophy due to Age-related macular degeneration (AMD).

Detailed Description

This was an open label first-in-human Phase I/II multicenter study to evaluate the safety, dose response and efficacy of GT005 in participants with Geographic atrophy (GA) due to Age-related macular degeneration (AMD).

The study treatment GT005 consists of an Adeno-associated virus serotype 2 (AAV2) expressing human complement factor I (hCFI). The treatment was administered as a single subretinal administration in one eye - the "study eye". Both eyes were assessed at the screening visit. If both eyes meet the eligibility criteria, the study eye will be the worse seeing eye, or the eye with the largest geographic atrophy (GA) lesion area for eyes with equivalent visual acuity, unless the participant (in consultation with the surgeon) expresses an alternative preference.

The study was conducted in 4 parts: in Part 1 and Part 2 GT005 was administered subretinally via transvitreal procedure; in Part 3 and 4 GT005 was delivered subretinally via a suprachoroidal cannulation with the Orbit Subretinal delivery system (SDS). The Orbit SDS is a 510(k) cleared device in the US, whereby Parts 3 and 4 were only conducted at US sites. The treatment consisted in 3 dose levels: low dose, 2E10 vector genomes (vg); medium dose, 5E10 vg; and high dose, 2E11 vg.

The study consisted of up to 13 visits over a 5-year period. All participants were assessed for the occurrence of treatment emergent adverse events (AE)s at each visit and underwent visual function and retinal imaging assessments and biological sampling as per the schedule of assessments.

This study was conducted in compliance with Independent ethics committees (IECs) / Institutional review boards (IRBs), informed consent regulations, the Declaration of Helsinki, nternational Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) Guidelines, and the Food and Drug Administration (FDA) guidance.

Conditions

Dry Age-related Macular Degeneration; Macular Degeneration; Retinal Disease; Eye Diseases; Retinal Degeneration; Geographic Atrophy; Macular Atrophy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

GT005 2E10 vg via Transvitreal Procedure

GT005 2E10 vg via Transvitreal Procedure

Group Type: EXPERIMENTAL

GT005

Intervention Type: BIOLOGICAL

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 5E10 vg via Transvitreal Procedure

GT005 5E10 vg via Transvitreal Procedure

Group Type: EXPERIMENTAL

GT005

Intervention Type: BIOLOGICAL

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 2E11 vg via Transvitreal Procedure

GT005 2E11 vg via Transvitreal Procedure

Group Type: EXPERIMENTAL

GT005

Intervention Type: BIOLOGICAL

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 5E10 vg with Orbit Subretinal Delivery System

GT005 5E10 vg with Orbit Subretinal Delivery System

Group Type: EXPERIMENTAL

GT005 / Device: Orbit™ Subretinal Delivery System

Intervention Type: DEVICE

GT005 is a recombinant, non-replicating AAV2 expressing human complement factor I (CFI).

A single dose of GT005 was administered with subretinal injection via suprachoroidal cannulation approach.

Device: Orbit™ Subretinal Delivery System

GT005 2E11 vg with Orbit Subretinal Delivery System

GT005 2E11 vg with Orbit Subretinal Delivery System

Group Type: EXPERIMENTAL

GT005 / Device: Orbit™ Subretinal Delivery System

Intervention Type: DEVICE

GT005 is a recombinant, non-replicating AAV2 expressing human complement factor I (CFI).

A single dose of GT005 was administered with subretinal injection via suprachoroidal cannulation approach.

Device: Orbit™ Subretinal Delivery System

Interventions

GT005

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.

Intervention Type: BIOLOGICAL

GT005 / Device: Orbit™ Subretinal Delivery System

GT005 is a recombinant, non-replicating AAV2 expressing human complement factor I (CFI).

A single dose of GT005 was administered with subretinal injection via suprachoroidal cannulation approach.

Device: Orbit™ Subretinal Delivery System

Intervention Type: DEVICE

Eligibility Criteria

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

• Minimum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Gyroscope Therapeutics Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chief Medical Officer

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Midwest Eye Institute

Indianapolis, Indiana, United States

Wolfe Eye Clinic

West Des Moines, Iowa, United States

Ophthalamic Consultants of Boston (OCB)

Boston, Massachusetts, United States

Pepose Vision Institute

Chesterfield, Missouri, United States

Sierra Eye Associates

Reno, Nevada, United States

Cincinnati Eye Institute

Cincinnati, Ohio, United States

Mid-Atlantic Retina

Philadelphia, Pennsylvania, United States

Bristol Eye Hospital

Bristol, , United Kingdom

Retina Clinic London

London, , United Kingdom

Moorfields Eye Hospital

London, , United Kingdom

Manchester Eye Hospital

Manchester, , United Kingdom

Oxford University Hospital

Oxford, , United Kingdom

Sunderland Eye Infirmary

Sunderland, , United Kingdom

Countries

United States; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 33750925 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=2646

A Plain Language Trial Summary is available on www.novctrd.com

https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=18286

Novartis Clinical Trial Results

Other Identifiers

CPPY988A12101

Identifier Type: OTHER

Identifier Source: secondary_id

GT005-01

Identifier Type: -

Identifier Source: org_study_id