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

NCT03846193 | Terminated Phase 1 Results DMC FDA Drug FDA Device

• 2 other identifiers: GT005-01CPPY988A12101
• Study Type: interventional
• Target: 56
• Locations: 2 countries
• Sites: 13

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).

Conditions

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

Keywords

Dry Age-related Macular Degeneration (Dry AMD); AMD; Atrophic AMD; Geographic Atrophy (GA); Dry-AMD; Dry AMD

Outcome Measures

Primary Outcomes (3)

• Ocular Treatment Emergent Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye

  An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject. A TEAE is defined as any AE that develops after randomization or any AE already present that worsens following randomization. The primary summaries of AEs are based on TEAEs. System organ classes are sorted alphabetically, and preferred terms are sorted by decreasing overall frequency within system organ class.

  Adverse events are reported from the single dose of study medication administration until end of study treatment plus 240 weeks post treatment, up to a maximum timeframe of approximately 240 weeks.

• Summary of Non-Ocular Treatment Emergent Adverse Events

  An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject. A TEAE is defined as any AE that develops after randomization or any AE already present that worsens following randomization. The primary summaries of AEs are based on TEAEs.

  Adverse events are reported from the single dose of study medication administration until end of study treatment plus 240 weeks post treatment, up to a maximum timeframe of approximately 240 weeks.

• Summary of Ocular Serious Treatment-Emergent Adverse Events in the Study Eye by System Organ Class and Preferred

  An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject. A TEAE is defined as any AE that develops after randomization or any AE already present that worsens following randomization. The primary summaries of AEs are based on TEAEs.

  Adverse events are reported from the single dose of study medication administration until end of study treatment plus 240 weeks post treatment, up to a maximum timeframe of approximately 240 weeks.

Secondary Outcomes (14)

• Best Corrected Visual Acuity (BCVA) (in Early Treatment Diabetic Retinopathy Study (ETDRS) Letters) in the Study Eye

  Up to Week 240

• Low-Luminance Deficit Best Corrected Visual Acuity (BCVA-LLVA) (in Early Treatment Diabetic Retinopathy Study (ETDRS) Letters) in the Study Eye

  Up to Week 240

• Macular Sensitivity Parameters by Mesopic Microperimetry (MP) Over Time in the Study Eye - MP Bivariate Contour Ellipse Area (BCEA) 63 Area (deg2)

  Up to Week 240

• Macular Sensitivity Parameters by Mesopic Microperimetry (MP) Over Time in the Study Eye - MP Bivariate Contour Ellipse Area (BCEA) 95 Area (deg2)

  Up to Week 240

• Macular Sensitivity Parameters by Mesopic Microperimetry (MP) Over Time in the Study Eye - MP Mean Sensitivity Decibel (dB)

  Up to Week 240

Study Arms (5)

GT005 2E10 vg via Transvitreal Procedure

EXPERIMENTAL

GT005 2E10 vg via Transvitreal Procedure

Biological: GT005

GT005 5E10 vg via Transvitreal Procedure

EXPERIMENTAL

GT005 5E10 vg via Transvitreal Procedure

Biological: GT005

GT005 2E11 vg via Transvitreal Procedure

EXPERIMENTAL

GT005 2E11 vg via Transvitreal Procedure

Biological: GT005

GT005 5E10 vg with Orbit Subretinal Delivery System

EXPERIMENTAL

GT005 5E10 vg with Orbit Subretinal Delivery System

Device: GT005 / Device: Orbit™ Subretinal Delivery System

GT005 2E11 vg with Orbit Subretinal Delivery System

EXPERIMENTAL

GT005 2E11 vg with Orbit Subretinal Delivery System

Device: GT005 / Device: Orbit™ Subretinal Delivery System

Interventions

GT005 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 2E10 vg via Transvitreal Procedure; GT005 2E11 vg via Transvitreal Procedure; GT005 5E10 vg via Transvitreal Procedure

GT005 / Device: Orbit™ Subretinal Delivery System 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 5E10 vg with Orbit Subretinal Delivery System

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 consent to study participation
• 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)
• 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
• GA lesion(s) in the study eye must reside completely within the FAF fundus image
• 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
• Aged ≥55 years
• Able to attend all study visits and complete the study procedures
• 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)

You may not qualify if:

• 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:
• 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
• Presence of moderate/severe non-proliferative diabetic retinopathy or worse 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 aluminum 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 more than two topical agents; a history of glaucoma-filtering or valve surgery is also excluded
• Axial myopia of greater than -8 diopters in the study eye
• 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
• Have received a gene or cell therapy at any time
• Have a contraindication to the specified protocol corticosteroid regimen
• 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
• 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

Sponsors & Collaborators

• Gyroscope Therapeutics Limited: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (13)

Midwest Eye Institute

Indianapolis, Indiana, 46290, United States

Location

Wolfe Eye Clinic

West Des Moines, Iowa, 50266, United States

Location

Ophthalamic Consultants of Boston (OCB)

Boston, Massachusetts, 02114, United States

Location

Pepose Vision Institute

Chesterfield, Missouri, 63017, United States

Location

Sierra Eye Associates

Reno, Nevada, 89502, United States

Location

Cincinnati Eye Institute

Cincinnati, Ohio, 45242, United States

Location

Mid-Atlantic Retina

Philadelphia, Pennsylvania, 19107, United States

Location

Bristol Eye Hospital

Bristol, United Kingdom

Location

Retina Clinic London

London, W1G 7LA, United Kingdom

Location

Moorfields Eye Hospital

London, United Kingdom

Location

Manchester Eye Hospital

Manchester, United Kingdom

Location

Oxford University Hospital

Oxford, United Kingdom

Location

Sunderland Eye Infirmary

Sunderland, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 33750925 DERIVED

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com
• Novartis Clinical Trial Results

MeSH Terms

Conditions

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

Condition Hierarchy (Ancestors)

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

Study Officials

• Chief Medical Officer

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A dose escalation study of the safety and efficacy of a single subretinal injection of GT005 in subjects with Macular Atrophy due to AMD

Study Record Dates

• First Submitted: February 13, 2019
• First Posted: February 19, 2019
• Study Start: December 17, 2018
• Primary Completion: June 25, 2024
• Study Completion: June 25, 2024
• Last Updated: January 28, 2026
• Results First Posted: August 24, 2025

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

US (7); GB (6)