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

• ClinicalTrials.gov Identifier: NCT03846193
• Recruitment Status: Active, not recruiting
• First Posted: February 19, 2019
• Last Update Posted: March 23, 2023
• Sponsor: Gyroscope Therapeutics Limited
• Collaborator: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Gyroscope Therapeutics Limited

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; Device: GT005/ Device: Orbit™ Subretinal Delivery System	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, with the option to be followed for a further 4 years in long-term follow up after completing week 48.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 56 participants
• Allocation: Non-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 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: December 17, 2018
• Estimated Primary Completion Date: May 23, 2023
• Estimated Study Completion Date: January 19, 2027

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

Outcome Measures

Primary Outcome Measures :

1. Incidence of ocular and non-ocular Treatment Emergent AEs (TEAEs) and Treatment-Emergent Serious AEs (TESAEs) Severe Adverse Events (TEAE/TESAE) [ Time Frame: 48 weeks ]
   Proportion of patients with TEAEs/TESAEs after subretinal injection of GT005

Secondary Outcome Measures :

1. Long-term safety of GT005 at 3 doses [ Time Frame: 240 weeks ]
   Incidence of ocular and non-ocular treatment-emergent AEs (TEAEs) and treatment-emergent serious AEs (TESAEs) up to 240 weeks
2. Visual Acuity [ Time Frame: 240 weeks ]
   Change from baseline in BCVA (Best Corrected Visual Acuity) and LLVA (Low Luminance Visual Acuity) score via ETDRS (Early Treatment Diabetic Retinopathy Study) chart
3. Macular Sensitivity [ Time Frame: 240 weeks ]
   Change from baseline in macular sensitivity as assessed by mesopic Microperimetry
4. Geographic Atrophy [ Time Frame: 240 weeks ]
   Change from baseline in GA size as assessed by fundus autofluorescence
5. Rate of successful delivery of Balanced Salt Solution (BSS) or BSS PLUS to the subretinal space (US only) [ Time Frame: Day 1 ]
   Proportion of subjects with successful delivery of BSS or BSS PLUS to subretinal space
6. Rate of successful delivery of GT005 to the subretinal space (US only) [ Time Frame: Day 1 ]
   Proportion of subjects with successful delivery of GT005 to subretinal space
7. Incidence of device-related AEs and SAEs (US only) [ Time Frame: Day 1 ]
   Proportion of subjects with device related AEs and SAEs after subretinal delivery with Orbit SDS

Eligibility Criteria

• Ages Eligible for Study: 55 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Indiana

Midwest Eye Institute

Indianapolis, Indiana, United States, 46290

United States, Iowa

Wolfe Eye Clinic

West Des Moines, Iowa, United States, 50266

United States, Massachusetts

Ophthalamic Consultants of Boston (OCB)

Boston, Massachusetts, United States, 02114

United States, Missouri

Pepose Vision Institute

Chesterfield, Missouri, United States, 63017

United States, Nevada

Sierra Eye Associates

Reno, Nevada, United States, 89502

United States, Ohio

Cincinnati Eye Institute

Cincinnati, Ohio, United States, 45242

United States, Pennsylvania

Mid-Atlantic Retina

Philadelphia, Pennsylvania, United States, 19107

United Kingdom

Bristol Eye Hospital

Bristol, United Kingdom

Retina Clinic London

London, United Kingdom, W1G 7LA

Moorfields Eye Hospital

London, United Kingdom

Manchester Eye Hospital

Manchester, United Kingdom

Oxford University Hospital

Oxford, United Kingdom

Sunderland Eye Infirmary

Sunderland, United Kingdom

Sponsors and Collaborators

Gyroscope Therapeutics Limited

Novartis Pharmaceuticals

Investigators

• Study Director: Chief Medical Officer; Novartis Pharmaceuticals

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Gyroscope Therapeutics Limited
• ClinicalTrials.gov Identifier: NCT03846193
• Other Study ID Numbers: GT005-01
• First Posted: February 19, 2019
• Last Update Posted: March 23, 2023
• Last Verified: March 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Gyroscope Therapeutics Limited:

Dry Age-related Macular Degeneration (Dry AMD); AMD; Atrophic AMD; Geographic Atrophy (GA); Dry-AMD; Dry AMD

Additional relevant MeSH terms:

Macular Degeneration; Eye Diseases; Geographic Atrophy; Retinal Diseases; Retinal Degeneration; Anetoderma; Atrophy; Pathological Conditions, Anatomical; Eye Diseases, Hereditary; Connective Tissue Diseases; Skin Abnormalities; Skin Diseases