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

• ClinicalTrials.gov Identifier: NCT04566445
• Recruitment Status: Active, not recruiting
• First Posted: September 28, 2020
• Last Update Posted: March 20, 2024
• Sponsor: Gyroscope Therapeutics Limited
• Collaborator: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Gyroscope Therapeutics Limited

Tracking Information

• First Submitted Date: September 9, 2020
• First Posted Date: September 28, 2020
• Last Update Posted Date: March 20, 2024
• Actual Study Start Date: September 28, 2020
• Estimated Primary Completion Date: May 31, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 14, 2022)

Progression of geographic atrophy [ Time Frame: 72 weeks ]

The change from baseline to Week 72 in GA area as measured by fundus autofluorescence (FAF)

Original Primary Outcome Measures (submitted: September 22, 2020)

Progression of geographic atrophy [ Time Frame: 48 weeks ]

The change from baseline to Week 48 in GA area as measured by fundus fluorescence (FAF)

Current Secondary Outcome Measures (submitted: December 14, 2022)

• Progression of geographic atrophy [ Time Frame: 96 weeks ]
  The change from baseline through Week 96 in GA area as measured by fundus autofluorescence (FAF)
• Evaluation of the safety and tolerability of GT005 [ Time Frame: 96 weeks ]
  Frequency of treatment emergent adverse events (AEs)
• Evaluation of the effect of GT005 on retinal anatomical measures [ Time Frame: 96 weeks ]
  Change in retinal morphology on multimodal imaging
• Evaluation of the effect of GT005 on functional measures [ Time Frame: 96 weeks ]
  Change in best corrected visual acuity (BCVA) Score via the early treatment for diabetic retinopathy (ETDRS) chart
• Evaluation of the effect of GT005 on functional measures [ Time Frame: 96 weeks ]
  Change in low luminance difference (LLD) via the ETDRS chart
• Evaluation of the effect of GT005 on visual function [ Time Frame: 96 weeks ]
  Change in reading performance as assessed by Minnesota low-vision reading test (MNRead) chart
• Evaluation of the effect of GT005 on visual function [ Time Frame: 96 weeks ]
  Change in functional reading independence (FRI) index
• Evaluation of the effect of GT005 on patient-reported outcomes [ Time Frame: 96 weeks ]
  Change in quality of life measured on the Visual Function Questionnaire-25 (VFQ-25)

Original Secondary Outcome Measures (submitted: September 22, 2020)

• Frequency of treatment emergent adverse events (TEAEs) [Safety and Tolerability of GT005] [ Time Frame: 48 weeks ]
• Change on ophthalmic examination [Safety and Tolerability of GT005] [ Time Frame: 48 weeks ]
• Change in imaging modalities [Safety and Tolerability of GT005] [ Time Frame: 48 weeks ]
• Change in best corrected visual acuity (BCVA) [Safety and Tolerability of GT005] [ Time Frame: 48 weeks ]
• Evaluation of the effect of GT005 on retinal anatomical measures [ Time Frame: 48 weeks ]
  Change in retinal microstructures on spectral domain optical coherence tomography (SD-OCT)
• Evaluation of the effect of GT005 on retinal anatomical measures [ Time Frame: 48 weeks ]
  Change in area of nascent GA on SD-OCT
• Evaluation of the effect of GT005 on retinal anatomical measures [ Time Frame: 48 weeks ]
  Change in GA morphology on colour fundus photography (CFP)
• Evaluation of the effect of GT005 on functional measures [ Time Frame: 48 weeks ]
  Macular sensitivity as assessed by mesopic microperimetry
• Evaluation of the effect of GT005 on functional measures [ Time Frame: 48 weeks ]
  Change in BCVA Score via the early treatment for diabetic retinopathy (ETDRS) chart
• Evaluation of the effect of GT005 on functional measures [ Time Frame: 48 weeks ]
  Change in low luminance difference (LLD) via the ETDRS chart
• Evaluation of the effect of GT005 on functional vision [ Time Frame: 48 weeks ]
  Change in reading performance as assessed by Minnesota low-vision reading test (MNRead) chart
• Evaluation of the effect of GT005 on functional vision [ Time Frame: 48 weeks ]
  Change in functional reading independence index (FRI index)
• Evaluation of the effect of GT005 on patient-reported outcomes [ Time Frame: 48 weeks ]
  Change in quality of life measured on the Visual Functioning Questionnaire-25 (VFQ-25)
• Evaluation of the effects of GT005 on the progression of GA, in each genetically defined subgroup(s) [ Time Frame: 48 weeks ]
  Change from baseline to Week 48 in GA area as measured by FAF

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: HORIZON: A Phase II Study to Evaluate the Safety and Efficacy of Two Doses of GT005
• Official Title: HORIZON: A Phase II, Open-label, Outcomes-assessor Masked, Multicentre, Randomised, Controlled Study to Evaluate the Safety and Efficacy of Two Doses of GT005 Administered as a Single Subretinal Injection in Subjects With Geographic Atrophy Secondary to Dry Age-related Macular Degeneration
• Brief Summary: 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).

Detailed Description

This is a Phase 2, open-label, outcomes-assessor masked, multicentre, randomised, controlled 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 and a 96-week study period.

Subjects will be randomised to one of two groups; GT005 or the untreated control group.

• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

This is a Phase II, open-label, outcomes-assessor masked, multicentre, randomised, controlled 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.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Quadruple (Participant, Care Provider, Investigator, Outcome Assessor). The overall objectives of the study are to evaluate the safety and efficacy (anatomical and functional visual outcomes) of two doses of GT005 in genetically defined subjects with GA due to AMD.

Primary Purpose: Treatment

• Condition: Dry Age-related Macular Degeneration

Intervention

• Drug: GT005: Medium Dose
  The study will test two doses of GT005: Medium Dose and High Dose.
• Drug: GT005: High Dose
  The study will test two doses of GT005: Medium Dose and High Dose.

Study Arms

• Experimental: GT005 Medium Dose
  Approximately 83 subjects are planned, with subjects randomised to GT005 Medium Dose.
  Intervention: Drug: GT005: Medium Dose
• Experimental: GT005 High Dose
  Approximately 83 subjects are planned, with subjects randomised to GT005 High Dose.
  Intervention: Drug: GT005: High Dose
• No Intervention: Untreated control
  Approximately 83 subjects are planned, with subjects randomised to untreated control.

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: December 14, 2022): 255
• Original Estimated Enrollment (submitted: September 22, 2020): 180
• Estimated Study Completion Date: May 31, 2024
• Estimated Primary Completion Date: May 31, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Able and willing to give written informed consent
2. Age ≥55 years
3. a. In Stage 1: 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; b. In Stage 2: Have a clinical diagnosis of GA secondary to AMD in the study eye, as determined by the Investigator, that is non-foveal, as determined by the central reading centre, or has a CFI rare variant genotype and meets inclusion criteria 3a, and a diagnosis of AMD in the contralateral eye (except if monocular)
4. GA lesion(s) within an acceptable size on FAF, in the study eye
5. The GA lesion 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
7. Have a BCVA of ≥24 letters (6/95 or 20/320 Snellen acuity equivalent), using ETDRS charts, in the study eye
8. a. In Stage 1: Meet one of the pre-specified AMD genetic subgroup criteria; b. In Stage 2: Genotyping is not required for study eligibility
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 (not required for postmenopausal women) or provide documentation of being surgically sterilised

Exclusion Criteria:

1. a. In Stage 1: Carriers of excluded genetic variants; b. In Stage 2: Subjects are excluded if they have a clinical diagnosis of Stargardt Disease or other retinal dystrophies
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 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, uncontrolled intraocular pressure (IOP), despite use of two or more topical agents; or a history of glaucoma-filtering or valve surgery
8. Axial myopia of greater than -8 diopters in the study eye
9. 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
10. Have received a gene or cell therapy at any time.
11. Have a contraindication to the protocol specified corticosteroid regimen
12. Are unwilling to use two forms of contraception (one of which being a barrier method) for 90 days post-dosing, if relevant
13. 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
14. 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 55 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, France, Germany, Poland, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT04566445
• Other Study ID Numbers: GT005-03; CPPY988A12201 ( Other Identifier: Novartis )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Gyroscope Therapeutics Limited
• Original Responsible Party: Same as current
• Current Study Sponsor: Gyroscope Therapeutics Limited
• Original Study Sponsor: Same as current
• Collaborators: Novartis Pharmaceuticals
• Investigators: Not Provided
• PRS Account: Gyroscope Therapeutics Limited
• Verification Date: March 2024