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).
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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
56
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 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
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
...and 3 more locations
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.
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.
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.
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.
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.
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.
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.
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
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.
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)
Macular sensitivity as assessed by mesopic Microperimetry. Mesopic Microperimetry (MP) Bivariate contour ellipse area (BCEA) 63 Area.
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)
Macular sensitivity as assessed by mesopic Microperimetry. Mesopic Microperimetry (MP) Bivariate contour ellipse area (BCEA) 95 Area.
Time frame: 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
Time frame: 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
Time frame: Up to Week 240
Macular Sensitivity Parameters by Mesopic Microperimetry (MP) Over Time in the Study Eye - MP Percent Fixation Loss (%)
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Macular sensitivity as assessed by mesopic Microperimetry
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
Change from baseline in GA size as assessed by fundus autofluorescence
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
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.
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
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Day 1