Dry Age-related Macular DegenerationPhase 1/2NCT03846193
FOCUS: A Phase I/II First in Human Study to Evaluate the Safety and Efficacy of GT005 Administered in Subjects With Dry AMD
A Phase 1/2 study testing GT005 and GT005 / Device: Orbit™ Subretinal Delivery System in people with Dry Age-related Macular Degeneration and Macular Degeneration, run by Gyroscope Therapeutics Limited at 13 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 55 years and older
- Conditions the study is for
- Dry Age-related Macular Degeneration, Macular Degeneration, Retinal Disease
- What is being tested?
- GT005 and GT005 / Device: Orbit™ Subretinal Delivery System
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 13 sitesin 2 countries
- Study dates
- 17 Dec 2018to 25 Jun 2024
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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)
Who cannot join
- 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
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- 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
- 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
Trial locations and contacts
13 sites in 2 countries.
13 sites in 2 countries
United States7 sites
Ophthalamic Consultants of Boston (OCB)
Boston, Massachusetts, 02114
Pepose Vision Institute
Chesterfield, Missouri, 63017
Cincinnati Eye Institute
Cincinnati, Ohio, 45242
Midwest Eye Institute
Indianapolis, Indiana, 46290
Mid-Atlantic Retina
Philadelphia, Pennsylvania, 19107
Sierra Eye Associates
Reno, Nevada, 89502
Wolfe Eye Clinic
West Des Moines, Iowa, 50266
United Kingdom6 sites
Bristol Eye Hospital
Bristol
Retina Clinic London
London, W1G 7LA
Moorfields Eye Hospital
London
Manchester Eye Hospital
Manchester
Oxford University Hospital
Oxford
Sunderland Eye Infirmary
Sunderland
About this study
Official title: 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 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).
Read the 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
- Being tested
- GT005, GT005 / Device: Orbit™ Subretinal Delivery System
- Keywords
- Dry Age-related Macular Degeneration (Dry AMD), AMD, Atrophic AMD, Geographic Atrophy (GA), Dry-AMD, Dry AMD
- Medical subject headings
- Macular Degeneration, Retinal Diseases, Eye Diseases, Retinal Degeneration, Geographic Atrophy, Anetoderma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GT005Biological
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 / Device: Orbit™ Subretinal Delivery SystemDevice
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
| Study group | Role | What they receive |
|---|---|---|
| GT005 2E10 vg via Transvitreal Procedure | Experimental | GT005 2E10 vg via Transvitreal Procedure Receives: Biological: GT005 |
| GT005 5E10 vg via Transvitreal Procedure | Experimental | GT005 5E10 vg via Transvitreal Procedure Receives: Biological: GT005 |
| GT005 2E11 vg via Transvitreal Procedure | Experimental | GT005 2E11 vg via Transvitreal Procedure Receives: Biological: GT005 |
| GT005 5E10 vg with Orbit Subretinal Delivery System | Experimental | GT005 5E10 vg with Orbit Subretinal Delivery System Receives: Device: GT005 / Device: Orbit™ Subretinal Delivery System |
| GT005 2E11 vg with Orbit Subretinal Delivery System | Experimental | GT005 2E11 vg with Orbit Subretinal Delivery System Receives: Device: GT005 / Device: Orbit™ Subretinal Delivery System |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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
Best corrected visual acuity (BCVA) was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts.
Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
Measured: 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
Low-Luminance Deficit best corrected visual acuity (BCVA-LLVA) was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts.
Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
Measured: 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)
Macular sensitivity as assessed by mesopic Microperimetry.
Mesopic Microperimetry (MP) Bivariate contour ellipse area (BCEA) 63 Area.
Measured: 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)
Macular sensitivity as assessed by mesopic Microperimetry.
Mesopic Microperimetry (MP) Bivariate contour ellipse area (BCEA) 95 Area.
Measured: Up to Week 240
Macular Sensitivity Parameters by Mesopic Microperimetry (MP) Over Time in the Study Eye - MP Mean Sensitivity Decibel (dB)
Macular sensitivity as assessed by mesopic Microperimetry
Measured: Up to Week 240
Macular Sensitivity Parameters by Mesopic Microperimetry (MP) Over Time in the Study Eye - MP Number of Scotomatous Points
Macular sensitivity as assessed by mesopic Microperimetry
Measured: Up to Week 240
Macular Sensitivity Parameters by Mesopic Microperimetry (MP) Over Time in the Study Eye - MP Percent Fixation Loss (%)
Macular sensitivity as assessed by mesopic Microperimetry
Measured: Up to Week 240
Change From Baseline Over Time in Square Root of Geographic Atrophy Area Size (mm) Via FAF in the Study Eye
Change from baseline in GA size as assessed by fundus autofluorescence
Measured: Up to Week 240
Delivery of GT005 to the Subretinal Space - Rate of Successful Delivery, % (US Only) Via the Orbit Subretinal Delivery System (SDS) Device
The rate of successful delivery is an evaluation limited to the administration performed using the Orbit Subretinal Delivery System (SDS) device, which is a 510(k) cleared device in the US.
The rate of successful delivery of GT005 is the number of full doses delivered divided by number of Orbit devices used.
This endpoint evaluates the surgical procedure with the Orbit device, and it is independent of the dose administered, as the volume of GT005 administered was consistent across all arms and cohorts.
The delivery was attempted in 28 pts but was only successful in 25 pts. Of 3 pts where the GT005 delivery via Orbit SDS arms was not successful, 2 were treated via the transvitreal procedure, and 1 was disc. from treatment. (For 1 of the 3 pts, BSS delivery was successful, but not GT005 delivery.) In all other efficacy tables, these 2 pts who were treated via the transvitreal procedure are included in the 1 of the 3 Transvitreal Procedure arms and not 1 of the 2 Orbit SDS arms.
Measured: Day 1
Delivery of Balanced Salt Solution (BSS) or BSS PLUS (BSS+) to the Subretinal Space - Rate of Successful Delivery, % (US Only) Via the Orbit Subretinal Delivery System (SDS) Device
The rate of successful delivery is an evaluation limited to the administration performed using the Orbit Subretinal Delivery System (SDS) device, which is a 510(k) cleared device in the US.
The rate of successful delivery of BSS was the number of full doses delivered divided by number of Orbit devices used.
This endpoint evaluates the surgical procedure with the Orbit device, and it is independent of the dose administered, as the volume of BSS administered was consistent across all arms and cohorts.
The delivery was attempted in 28 pts but was only successful in 25 pts. Of 3 pts where the GT005 delivery via Orbit SDS arms was not successful, 2 were treated via the transvitreal procedure, and 1 was disc. from treatment. (For 1 of the 3 pts, BSS delivery was successful, but not GT005 delivery.) In all other efficacy tables, these 2 pts who were treated via the transvitreal procedure are included in the 1 of the 3 Transvitreal Procedure arms and not 1 of the 2 Orbit SDS arms.
Measured: Day 1
Summary of Ocular Treatment-Emergent Adverse Events Related to Surgical Procedure in the Study Eye
Subjects with device related AEs and SAEs after subretinal delivery with Orbit SDS.
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.
Measured: Day 1
Summary of Non-Ocular Treatment-Emergent Adverse Events Related to Surgical Procedure
Subjects with device related AEs and SAEs after subretinal delivery with Orbit SDS.
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.
Measured: Day 1
Summary of Ocular Serious Treatment-Emergent Adverse Events Related to Surgical Procedure in the Study Eye
Subjects with device related AEs and SAEs after subretinal delivery with Orbit SDS.
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.
Measured: Day 1
Summary of Non-Ocular Serious Treatment-Emergent Adverse Events Related to Surgical Procedure
Subjects with device related AEs and SAEs after subretinal delivery with Orbit SDS.
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.
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2019
- Study start17 Dec 2018
- Primary completion25 Jun 2024
- Study completion25 Jun 2024
Why it stopped: The study was terminated due to the interim analysis demonstrating lack of treatment efficacy.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Dry Age-related Macular DegenerationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- A dose escalation study of the safety and efficacy of a single subretinal injection of GT005 in subjects with Macular Atrophy due to AMD
- Masking
- None (open label)
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gyroscope Therapeutics Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Chief Medical Officer, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03846193
- Sponsor's protocol ID
- GT005-01
- Other IDs
- CPPY988A12101
- Status last verified
- Jan 2026
- First submitted
- 13 Feb 2019
- Last updated
- 28 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.
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.
PubMed 33750925
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03846193
- Acronym / sponsor ID
- GT005-01
- Conditions
- Dry Age-related Macular Degeneration, Macular Degeneration, Retinal Disease, Eye Diseases, Retinal Degeneration, Geographic Atrophy
- Keywords
- Dry Age-related Macular Degeneration (Dry AMD), AMD, Atrophic AMD, Geographic Atrophy (GA), Dry-AMD, Dry AMD
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated due to the interim analysis demonstrating lack of treatment efficacy.
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Gyroscope Therapeutics LimitedIndustry (pharma, biotech, devices)
- Collaborators
- Novartis Pharmaceuticals
- Study start
- 17 Dec 2018 (actual)
- Primary completion
- 25 Jun 2024 (actual)
- Study completion
- 25 Jun 2024 (actual)
- First posted
- 19 Feb 2019 (actual)
- Results
- Posted 24 Aug 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
- Model description
- A dose escalation study of the safety and efficacy of a single subretinal injection of GT005 in subjects with Macular Atrophy due to AMD
| Arm | Type | Receives |
|---|---|---|
| GT005 2E10 vg via Transvitreal Procedure | Experimental | Biological: GT005GT005 2E10 vg via Transvitreal Procedure |
| GT005 5E10 vg via Transvitreal Procedure | Experimental | Biological: GT005GT005 5E10 vg via Transvitreal Procedure |
| GT005 2E11 vg via Transvitreal Procedure | Experimental | Biological: GT005GT005 2E11 vg via Transvitreal Procedure |
| GT005 5E10 vg with Orbit Subretinal Delivery System | Experimental | Device: GT005 / Device: Orbit™ Subretinal Delivery SystemGT005 5E10 vg with Orbit Subretinal Delivery System |
| GT005 2E11 vg with Orbit Subretinal Delivery System | Experimental | Device: GT005 / Device: Orbit™ Subretinal Delivery SystemGT005 2E11 vg with Orbit Subretinal Delivery System |
Who may qualify
- Ages
- 55 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (16 listed)
- 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:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GT005GT005 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. | Biological | GT005 2E10 vg via Transvitreal Procedure, GT005 2E11 vg via Transvitreal Procedure, GT005 5E10 vg via Transvitreal Procedure |
| GT005 / Device: Orbit™ Subretinal Delivery SystemGT005 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 | Device | GT005 2E11 vg with Orbit Subretinal Delivery System, GT005 5E10 vg with Orbit Subretinal Delivery System |
Primary outcome
Ocular Treatment Emergent Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye
Time frame: 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.
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.
Summary of Non-Ocular Treatment Emergent Adverse Events
Time frame: 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.
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.
Summary of Ocular Serious Treatment-Emergent Adverse Events in the Study Eye by System Organ Class and Preferred
Time frame: 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.
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.
14 secondary outcomes
Best Corrected Visual Acuity (BCVA) (in Early Treatment Diabetic Retinopathy Study (ETDRS) Letters) in the Study Eye
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: Up to Week 240
Macular Sensitivity Parameters by Mesopic Microperimetry (MP) Over Time in the Study Eye - MP Mean Sensitivity Decibel (dB)
Time frame: Up to Week 240
Macular Sensitivity Parameters by Mesopic Microperimetry (MP) Over Time in the Study Eye - MP Number of Scotomatous Points
Time frame: Up to Week 240
Macular Sensitivity Parameters by Mesopic Microperimetry (MP) Over Time in the Study Eye - MP Percent Fixation Loss (%)
Time frame: Up to Week 240
Change From Baseline Over Time in Square Root of Geographic Atrophy Area Size (mm) Via FAF in the Study Eye
Time frame: Up to Week 240
Delivery of GT005 to the Subretinal Space - Rate of Successful Delivery, % (US Only) Via the Orbit Subretinal Delivery System (SDS) Device
Time frame: Day 1
Delivery of Balanced Salt Solution (BSS) or BSS PLUS (BSS+) to the Subretinal Space - Rate of Successful Delivery, % (US Only) Via the Orbit Subretinal Delivery System (SDS) Device
Time frame: Day 1
Summary of Ocular Treatment-Emergent Adverse Events Related to Surgical Procedure in the Study Eye
Time frame: Day 1
Summary of Non-Ocular Treatment-Emergent Adverse Events Related to Surgical Procedure
Time frame: Day 1
Summary of Ocular Serious Treatment-Emergent Adverse Events Related to Surgical Procedure in the Study Eye
Time frame: Day 1
Summary of Non-Ocular Serious Treatment-Emergent Adverse Events Related to Surgical Procedure
Time frame: Day 1
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33750925Dreismann 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.
- A Plain Language Trial Summary is available on www.novctrd.comLink provided by the sponsor.
- Novartis Clinical Trial ResultsLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chief Medical Officer study director
Novartis Pharmaceuticals
13 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing GT005 and GT005 / Device: Orbit™ Subretinal Delivery System in people with Dry Age-related Macular Degeneration and Macular Degeneration, run by Gyroscope Therapeutics Limited at 13 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ocular Treatment Emergent Adverse Events by Primary System Organ Class and Preferred Term for the Study Eye (time frame: 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.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03846193, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2026.