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

Macular Degeneration Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03846193
• Other study ID #: GT005-01
• Secondary ID: CPPY988A12101
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: December 17, 2018
• Est. completion date: June 28, 2024

Study information

• Verified date: January 2024
• Source: Gyroscope Therapeutics Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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, with the option to be followed for a further 4 years in long-term follow up after completing week 48.

This study is terminating early due to the interim analysis demonstrating lack of treatment efficacy. No additional subjects will be randomized or dosed. The trial is not ending early because of medical problems.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 56
• Est. completion date: June 28, 2024
• Est. primary completion date: June 28, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Biological:
• GT005
A recombinant non-replicating Adeno-Associated Viral (AAV) vector encoding a human complement factor
• GT005
A recombinant non-replicating Adeno-Associated Viral (AAV) vector encoding a human complement factor
• GT005
A recombinant non-replicating Adeno-Associated Viral (AAV) vector encoding a human complement factor
• GT005
A recombinant non-replicating Adeno-Associated Viral (AAV) vector encoding a human complement factor

Device:
• GT005/ Device: Orbit™ Subretinal Delivery System
A recombinant non-replicating Adeno-Associated Viral (AAV) vector encoding a human complement factor Device: Orbit™ Subretinal Delivery System
• GT005/ Device: Orbit™ Subretinal Delivery System
A recombinant non-replicating Adeno-Associated Viral (AAV) vector encoding a human complement factor Device: Orbit™ Subretinal Delivery System
• GT005/ Device: Orbit™ Subretinal Delivery System
A recombinant non-replicating Adeno-Associated Viral (AAV) vector encoding a human complement factor Device: Orbit™ Subretinal Delivery System

Locations

Country	Name	City	State
United Kingdom	Bristol Eye Hospital	Bristol
United Kingdom	Moorfields Eye Hospital	London
United Kingdom	Retina Clinic London	London
United Kingdom	Manchester Eye Hospital	Manchester
United Kingdom	Oxford University Hospital	Oxford
United Kingdom	Sunderland Eye Infirmary	Sunderland
United States	Ophthalamic Consultants of Boston (OCB)	Boston	Massachusetts
United States	Pepose Vision Institute	Chesterfield	Missouri
United States	Cincinnati Eye Institute	Cincinnati	Ohio
United States	Midwest Eye Institute	Indianapolis	Indiana
United States	Mid-Atlantic Retina	Philadelphia	Pennsylvania
United States	Sierra Eye Associates	Reno	Nevada
United States	Wolfe Eye Clinic	West Des Moines	Iowa

Sponsors (2)

Lead Sponsor	Collaborator
Gyroscope Therapeutics Limited	Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of ocular and non-ocular Treatment Emergent AEs (TEAEs) and Treatment-Emergent Serious AEs (TESAEs) Severe Adverse Events (TEAE/TESAE)	Proportion of patients with TEAEs/TESAEs after subretinal injection of GT005	240 weeks
Secondary	Long-term safety of GT005 at 3 doses	Incidence of ocular and non-ocular treatment-emergent AEs (TEAEs) and treatment-emergent serious AEs (TESAEs) up to 240 weeks	240 weeks
Secondary	Visual Acuity	Change from baseline in BCVA (Best Corrected Visual Acuity) and LLVA (Low Luminance Visual Acuity) score via ETDRS (Early Treatment Diabetic Retinopathy Study) chart	240 weeks
Secondary	Macular Sensitivity	Change from baseline in macular sensitivity as assessed by mesopic Microperimetry	240 weeks
Secondary	Geographic Atrophy	Change from baseline in GA size as assessed by fundus autofluorescence	240 weeks
Secondary	Rate of successful delivery of Balanced Salt Solution (BSS) or BSS PLUS to the subretinal space (US only)	Proportion of subjects with successful delivery of BSS or BSS PLUS to subretinal space	Day 1
Secondary	Rate of successful delivery of GT005 to the subretinal space (US only)	Proportion of subjects with successful delivery of GT005 to subretinal space	Day 1
Secondary	Incidence of device-related AEs and SAEs (US only)	Proportion of subjects with device related AEs and SAEs after subretinal delivery with Orbit SDS	Day 1