FocuS: First in Human Study to Evaluate the Safety and Efficacy of GT005 Administered in Subjects With Dry AMD

Sponsor

Gyroscope Therapeutics Limited (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03846193

Collaborator

(none)

Enrollment

Locations

Arms

93.5

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Dry Age-related Macular Degeneration Macular Degeneration Retinal Disease Eye Diseases Retinal Degeneration Geographic Atrophy Macular Atrophy	Biological: GT005 Biological: GT005 Biological: GT005 Biological: GT005 Device: GT005 Device: GT005 Device: GT005	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

65 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Intervention 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 AMDA 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)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 17, 2018

Anticipated Primary Completion Date :

Oct 1, 2022

Anticipated Study Completion Date :

Oct 1, 2026

Arms and Interventions

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 A recombinant non-replicating adeno-associated viral (AAV) vector encoding a human complement factor
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 A recombinant non-replicating adeno-associated viral (AAV) vector encoding a human complement factor
Experimental: GT005 Dose 1, 2 or 3 with Orbit Subretinal Delivery Sysem A single dose of GT005 will be administered with subretinal injection via suprachoroidal cannulation approach	Device: GT005 A recombinant non-replicating adeno-associated viral (AAV) vector encoding a human complement factor

Outcome Measures

Primary Outcome Measures

Incidence and severity of Treatment Emergent Adverse Events /Treatment Emergent Severe Adverse Events (TEAE/TESAE) [48 weeks]
Proportion of patients with TEAEs/TESAEs after subretinal injection of GT005

Secondary Outcome Measures

Geographic Atrophy [48 weeks]
Change from baseline in GA size measured in mm2
Retinal Drusen Volume [48 weeks]
Change from baseline in GA size measured in mm3
Macular Sensitivity [48 weeks]
Change from baseline in macular sensitivity measured in decibels (DB)
Monocular Reading Speed [48 weeks]
Change from baseline in monocular reading speed measured in words/min
Vector Shedding [48 weeks]
Change from baseline in vector titres measured in vector genome/ml
Complement factors [48 weeks]
Change from baseline in levels of complement factors, measured in nanograms/ml

Eligibility Criteria

Criteria

Ages Eligible for Study:

55 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Able and willing to give consent to study participation
Presence of Bilateral GA due to AMD on Color Fundus Photography (CFP)
Cohorts 1 to 3: GA lesions total size in the treatment eye must be

≥1.25mm2 and ≤17.5mm2

Cohorts 4 to 7: GA lesions total size must be ≥1.25mm2 and ≤17.5mm2 for both eyes

Cohorts 1 to 3: the GA lesion in the treatment eye must reside completely within the FAF fundus image

Cohorts 4 to 7: The GA lesion must reside completely within the FAF fundus image for both eyes

Cohorts 1 to 3: BCVA of ≤50 letters (6/36 Snellen acuity equivalent or worse) using ETDRS charts in the treatment eye

Cohorts 4 to 7: BCVA of ≥24 letters (6/95 and 20/320 Snellen acuity equivalent or better) using ETDRS charts in both eyes

Aged ≥55 years
Able to attend all study visits and complete the study procedures

Exclusion Criteria

Have evidence or history of choroidal neovascularization (CNV) in either eye
Presence of moderate/severe or worse non-proliferative, diabetic retinopathy in either eye
Have history of vitrectomy, sub-macular surgery, or macular photocoagulation in either 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 either eye
Presence of moderate to severe glaucomatous optic neuropathy in either 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 either eye
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Retina Vitreous Associates of Florida	Saint Petersburg	Florida	United States	33711
2	Wolfe Eye Clinic	West Des Moines	Iowa	United States	50266
3	Ophthalamic Consultants of Boston (OCB)	Boston	Massachusetts	United States	02114
4	Pepose Vision Institute	Chesterfield	Missouri	United States	63017
5	Sierra Eye Associates	Reno	Nevada	United States	89502
6	Cincinnati Eye Institute	Cincinnati	Ohio	United States	45242
7	Mid-Atlantic Retina	Philadelphia	Pennsylvania	United States	19107
8	Bristol Eye Hospital	Bristol		United Kingdom
9	London Vision Clinic	London		United Kingdom	W1G 7LA
10	Moorfields Eye Hospital	London		United Kingdom
11	Manchester Eye Hospital	Manchester		United Kingdom
12	Oxford University Hospital	Oxford		United Kingdom
13	Sunderland Eye Infirmary	Sunderland		United Kingdom