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

• Sponsor: Gyroscope Therapeutics Limited (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04566445
• Collaborator: (none)
• Enrollment: 250
• Locations: 62
• Arms: 3
• Anticipated Duration (Months): 61.1
• Patients Per Site: 4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Dry Age-related Macular Degeneration	Drug: GT005: Medium Dose; Drug: GT005: High Dose	Phase 2

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 250 participants
• 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.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
• 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 Age-related Macular Degeneration
• Actual Study Start Date: Sep 28, 2020
• Anticipated Primary Completion Date: Oct 31, 2024
• Anticipated Study Completion Date: Oct 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GT005 Medium Dose Approximately 83 subjects are planned, with subjects randomised to GT005 Medium Dose.	Drug: GT005: Medium Dose; The study will test two doses of GT005: Medium Dose and High Dose.
Experimental: GT005 High Dose Approximately 83 subjects are planned, with subjects randomised to GT005 High Dose.	Drug: GT005: High Dose; The study will test two doses of GT005: Medium Dose and High Dose.
No Intervention: Untreated control Approximately 83 subjects are planned, with subjects randomised to untreated control.

Outcome Measures

Primary Outcome Measures

1. Progression of geographic atrophy [48 weeks]

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

Secondary Outcome Measures

1. Progression of geographic atrophy [72 weeks and 96 weeks]

   The change from baseline to Week 72 and Week 96 in GA area as measured by fundus autofluorescence (FAF)

2. Evaluation of the safety and tolerability of GT005 [96 weeks]

   Frequency of treatment emergent adverse events (AEs)

3. Evaluation of the effect of GT005 on retinal anatomical measures [96 weeks]

   Change in retinal microstructures on optical coherence tomography (OCT)

4. Evaluation of the effect of GT005 on retinal anatomical measures [96 weeks]

   Change in presence of area of nascent GA on OCT

5. Evaluation of the effect of GT005 on retinal anatomical measures [96 weeks]

   Change in GA morphology on multimodal imaging

6. Evaluation of the effect of GT005 on functional measures [96 weeks]

   Macular sensitivity as assessed by mesopic microperimetry

7. Evaluation of the effect of GT005 on functional measures [96 weeks]

   Change in BCVA Score via the early treatment for diabetic retinopathy (ETDRS) chart

8. Evaluation of the effect of GT005 on functional measures [96 weeks]

   Change in low luminance difference (LLD) via the ETDRS chart

9. Evaluation of the effect of GT005 on visual function [96 weeks]

   Change in reading performance as assessed by Minnesota low-vision reading test (MNRead) chart

10. Evaluation of the effect of GT005 on visual function [96 weeks]

    Change in functional reading independence (FRI) index

11. Evaluation of the effect of GT005 on patient-reported outcomes [96 weeks]

    Change in quality of life measured on the Visual Functioning Questionnaire-25 (VFQ-25)

12. Evaluation of the effects of GT005 on the progression of GA, in each genetically defined subgroup(s) [96 weeks]

    Change from baseline to Week 48, Week 72, and Week 96 in GA area as measured by FAF

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Able and willing to give written informed consent

2. Age ≥55 years

3. 1. 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. 1. 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. 1. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Retinal Research Institute	Phoenix	Arizona	United States	85053
2	Retina Vitreous Associates Medical Group	Beverly Hills	California	United States	90211
3	Retina Consultants of Orange County	Fullerton	California	United States	92835
4	Northern California Retina Vitreous Associates	Mountain View	California	United States	94040
5	Byers Eye Institute at Stanford	Palo Alto	California	United States	94303
6	Retina Consultants San Diego	Poway	California	United States	92064
7	University of California- Davis Medical Group Eye Center	Sacramento	California	United States	95817
8	Southwest Retina Research Center	Durango	Colorado	United States	81303
9	Rand Eye Institute	Deerfield Beach	Florida	United States	33064
10	VitreoRetinal Associates of Gainesville	Gainesville	Florida	United States	32607
11	Bascom Palmer Eye Institute	Miami	Florida	United States	33136
12	Retina Vitreous Associates of Florida	Saint Petersburg	Florida	United States	33711
13	Southeast Retina Center	Augusta	Georgia	United States	30909
14	Georgia Retina PC	Marietta	Georgia	United States	30060
15	University Retina Macula Associates PC	Oak Forest	Illinois	United States	60452
16	Illinois Retina Associates	Oak Park	Illinois	United States	60304
17	Midwest Eye Institute Northside	Indianapolis	Indiana	United States	46290
18	Wolfe Eye Clinic	West Des Moines	Iowa	United States	50266
19	Retina Associates PA	Lenexa	Kansas	United States	66215
20	The Retina Care Center	Baltimore	Maryland	United States	21209
21	Ophthalmic Consultants of Boston	Boston	Massachusetts	United States	02114
22	Michigan Retina	Grand Blanc	Michigan	United States	48439
23	Associated Retinal Consultants PC	Royal Oak	Michigan	United States	48073
24	Sierra Eye Associates	Reno	Nevada	United States	89502
25	Harkness Eye Institute	New York	New York	United States	10032
26	Retina Associates of Western NY	Rochester	New York	United States	14620
27	Duke Eye Center	Durham	North Carolina	United States	27705
28	Cincinnati Eye Institute	Cincinnati	Ohio	United States	45242
29	Cleveland Clinic	Cleveland	Ohio	United States	44195
30	Oregon Retina	Eugene	Oregon	United States	97401
31	Casey Eye Institute - OHSU	Portland	Oregon	United States	97239
32	Erie Retina Research	Erie	Pennsylvania	United States	16507
33	Wills Eye Clinic	Philadelphia	Pennsylvania	United States	19107
34	Palmetto Eye	Columbia	South Carolina	United States	29212
35	SE Retina Associates	Knoxville	Tennessee	United States	37922
36	Charles Retina Institute	Memphis	Tennessee	United States	38138
37	Retina Consultants of Austin	Austin	Texas	United States	78705
38	Retina Foundation of the Southwest	Dallas	Texas	United States	75231
39	Texas Retina Associates	Dallas	Texas	United States	75231
40	Retina Consultants of Houston	Houston	Texas	United States	77030
41	Retinal Consultants of San Antonio	San Antonio	Texas	United States	78240
42	Retina Consultants of Houston	The Woodlands	Texas	United States	77384
43	Rocky Mountain Retina Consultants	Salt Lake City	Utah	United States	84107
44	University of Washington	Seattle	Washington	United States	98104
45	Retina Center Northwest	Silverdale	Washington	United States	98383
46	Sydney Eye Hospital	Sydney	New South Wales	Australia
47	The University of Melbourne - The Centre for Eye Research Australia (CERA)	Melbourne E.	Victoria	Australia
48	Centre Paradis Monticelli	Marseille	Alpes-Cote d'Azur	France	13008
49	CHU Hôpital F. Mitterrand	Dijon	Bourgogne-Franche-Comté	France	21079
50	CHU de Nantes - Hôtel-Dieu	Nantes	Pays De La Loire	France	44000
51	Universitaetsklinikum Tuebingen	Tuebingen	Baden Wurttemberg	Germany	72076
52	Universitaetsklinikum Schleswig-Holstein Campus Lübeck	Lübeck	Schleswig-Holstein	Germany	23562
53	Universitätsklinikum Bonn Augenklinik	Bonn		Germany	53127
54	Internationale Innovative Ophthalmochirurgie	Düsseldorf		Germany	40212
55	Oftalmika - Prywatna Klinika Okulistyczna	Bydgoszcz	Kujawsko-Pomorskie	Poland
56	Hospital Universitari General de Catalunya	Sant Cugat Del Vallès	Barcelona	Spain	08195
57	Clinica Baviera	Madrid	Comunidad De Madrid	Spain	28046
58	Clinica Universidad de Navarra	Pamplona		Spain	31008
59	Moorfields Eye Hospital	London		United Kingdom	EC1V 2PD
60	London Vision Clinic	London		United Kingdom	W1G 7LA
61	John Radcliffe Hospital	Oxford		United Kingdom	OX3 9DU
62	Sunderland Eye Infirmary	Sunderland		United Kingdom	SR2 9HP

Sponsors and Collaborators

• Gyroscope Therapeutics Limited

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gyroscope Therapeutics Limited
• ClinicalTrials.gov Identifier: NCT04566445
• Other Study ID Numbers: GT005-03
• First Posted: Sep 28, 2020
• Last Update Posted: Aug 2, 2022
• Last Verified: Aug 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Gyroscope Therapeutics Limited: Dry age-related macular degeneration; Geographic atrophy; Retinal disease; Eye disease; Retinal degeneration; Macular atrophy
• Additional relevant MeSH terms: Macular Degeneration; Geographic Atrophy

Study Results

No Results Posted as of Aug 2, 2022