EXPLORE: A Phase II Study to Evaluate the Safety and Efficacy of Two Doses of GT005

Gyroscope Therapeutics

Status and phase: Terminated; Phase 2

Conditions: Dry Age-related Macular Degeneration

Treatments: Drug: GT005; High Dose; Drug: GT005; Low Dose

Study type: Interventional

Funder types: Industry

Identifiers

NCT04437368

GT005-02

CPPY988A12202 (Other Identifier)

Details and patient eligibility

About

The purpose of this clinical study is to evaluate the safety and efficacy of two doses of GT005 administered as a single subretinal injection in subjects with geographic atrophy secondary to age-related macular degeneration (AMD).

Full description

This is a Phase 2, outcomes assessor-masked, multicentre, randomised study to evaluate the safety and efficacy of two doses of GT005 administered as a single subretinal injection in subjects with GA secondary to AMD.

The trial includes a screening period of up to 8 weeks followed by a 96-week study period.

Subjects will be randomised to one of two arms: GT005 or the untreated control group.

Part 1 is conducted in a genetically selective sub-group of patients with GA secondary to AMD.

Part 2 is conducted in a non-genetically selective sub-group of patients with GA secondary to AMD.

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.

Enrollment: 98 patients

Sex: All

Ages: 55+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Able and willing to give written informed consent

2. Age ≥55 years

3. 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)

4. Have GA lesion(s) total size between or equal to 1.25mm2 to 17.5mm2 in the study eye

5. The GA lesion(s) in the study eye must reside completely within the FAF image

6. Up to 25% of the enrolled study population 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

7. Have a BCVA of 24 letters (6/95 and 20/320 Snellen acuity equivalent) or better, using ETDRS charts, in the study eye

8. Part 1 Only: Subjects carrying a CFI rare variant genotype (minor allele frequency of ≤1%) previously associated with low serum CFI or subjects carrying an unreported CFI rare variant genotype that have tested to have a low serum CFI

9. Able to attend all study visits and complete the study procedures

10. Women of child-bearing potential must have a negative pregnancy test within 2 weeks prior to randomisation. 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. Subjects who have a clinical diagnosis of Stargardt Disease or other retinal dystrophies, confirmed by the central reading centre
2. Have a history, or evidence, of CNV in the study eye
3. Presence of moderate/severe or worse non-proliferative diabetic retinopathy in the study eye
4. Have history of vitrectomy, sub-macular surgery, or macular photocoagulation in the study eye
5. History of intraocular surgery in the study eye within 12 weeks prior to Screening (Visit 1). Yttrium aluminium garnet capsulotomy is permitted if performed >10 weeks prior to Visit 1
6. Have clinically significant cataract that may require surgery during the study period in the study eye
7. Presence of moderate to severe glaucomatous optic neuropathy in the study eye; uncontrolled IOP despite the use of two or more topical agents; a history of glaucoma-filtering or valve surgery is also excluded
8. Axial myopia of greater than -8 dioptres in the study eye
9. 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
10. Have a contraindication to specified protocol corticosteroid regimen
11. Have received any investigational and/or approved product(s) 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 in the study eye or systemically
12. Have received a gene or cell therapy at any time
13. Are unwilling to use two forms of contraception (one of which being a barrier method) for 90 days post-dosing, if relevant
14. 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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98 participants in 5 patient groups

Part 1 - GT005 Low Dose

Experimental group

Description:

Approximately 25 subjects are planned, with subjects randomised to GT005 Low Dose.

Treatment:

Drug: GT005; Low Dose

Drug: GT005; Low Dose

Part 1 - GT005 High Dose

Experimental group

Description:

Approximately 25 subjects are planned, with subjects randomised to GT005 High Dose.

Treatment:

Drug: GT005; High Dose

Part 1 - Untreated control

No Intervention group

Description:

Approximately 25 subjects are planned, with subjects randomised to untreated control.

Part 2 - GT005 Low Dose

Experimental group

Description:

Approximately 116 subjects are planned, with subjects randomised to Part 2 - GT005 Low Dose.

Treatment:

Drug: GT005; Low Dose

Drug: GT005; Low Dose

Part 2 - Untreated control

No Intervention group

Description:

Approximately 54 subjects are planned, with subjects randomised to untreated control.