Clinical trial NCT03846193: FOCUS: A Phase I/II First in Human Study to Evaluate the Safety and Efficacy of GT005 Administered in Subjects With Dry AMD
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
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
Lead sponsor: Gyroscope Therapeutics Limited
Sponsor class: INDUSTRY
Collaborators: name: Novartis Pharmaceuticals
First posted: 2019-02-19
Enrollment: 56
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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 AMD
Primary purpose: TREATMENT

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

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, 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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of ocular and non-ocular Treatment Emergent AEs (TEAEs) and Treatment-Emergent Serious AEs (TESAEs) Severe Adverse Events (TEAE/TESAE)
timeFrame: 240 weeks
Secondary outcomes:
measure: Long-term safety of GT005 at 3 doses
timeFrame: 240 weeks
measure: Visual Acuity
timeFrame: 240 weeks
measure: Macular Sensitivity
timeFrame: 240 weeks
measure: Geographic Atrophy
timeFrame: 240 weeks
measure: Rate of successful delivery of Balanced Salt Solution (BSS) or BSS PLUS to the subretinal space (US only)
timeFrame: Day 1
measure: Rate of successful delivery of GT005 to the subretinal space (US only)
timeFrame: Day 1
measure: Incidence of device-related AEs and SAEs (US only)
timeFrame: Day 1
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Midwest Eye Institute
state: Indiana
city: West Des Moines
country: United States
facility: Wolfe Eye Clinic
state: Iowa
city: Boston
country: United States
facility: Ophthalamic Consultants of Boston (OCB)
state: Massachusetts
city: Chesterfield
country: United States
facility: Pepose Vision Institute
state: Missouri
city: Reno
country: United States
facility: Sierra Eye Associates
state: Nevada
city: Cincinnati
country: United States
facility: Cincinnati Eye Institute
state: Ohio
city: Philadelphia
country: United States
facility: Mid-Atlantic Retina
state: Pennsylvania
city: Bristol
country: United Kingdom
facility: Bristol Eye Hospital
city: London
country: United Kingdom
facility: Retina Clinic London
city: London
country: United Kingdom
facility: Moorfields Eye Hospital
city: Manchester
country: United Kingdom
facility: Manchester Eye Hospital
city: Oxford
country: United Kingdom
facility: Oxford University Hospital
city: Sunderland
country: United Kingdom
facility: Sunderland Eye Infirmary
Study officials:
affiliation: Novartis Pharmaceuticals
name: Chief Medical Officer
role: STUDY_DIRECTOR
References:
citation: 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.