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TerminatedNCT04566445Updated Jan 28, 2026Results posted

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

A Phase 2 interventional study of GT005 in Dry Age-related Macular Degeneration, sponsored by Gyroscope Therapeutics Limited. Terminated at 62 sites in 7 countries. Open to participants aged 55 Years and older. Per ClinicalTrials.gov, last updated 2026-01-28.

Sponsored by Gyroscope Therapeutics Limited · Phase 2, Interventional, and Treatment

Why this study was terminated
Terminated for interim analysis demonstrating futility (trial highly unlikely to meet efficacy outcome). The trial is not ending early because of medical problems or concerns.
Phase
Phase 2
Study type
Interventional
Enrollment
255
Allocation
Randomized
Ages
55 Years and older
Sex
All
01

Study summary

The purpose of this clinical study was 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).

Read the detailed description

This was a Phase II, open-label, outcomes-assessor masked, multicenter, randomized, controlled study designed to evaluate the safety and efficacy of two doses of GT005 administered as a single-time subretinal injection in subjects with Geographic atrophy (GA) secondary to Age-related macular degeneration (AMD).

Approximately 250 subjects, across Stage 1 and Stage 2, were planned to be randomized to one of two doses of GT005 or the untreated control group.

Subjects entered the study had genotyping and serum Complement factor I (CFI) levels assessed either through participation in a previous Gyroscope sponsored study, or a Sponsor-approved laboratory during the HORIZON screening period. If both eyes are eligible; the eye with the worse visual acuity will be selected as the study eye. If subjects failed to meet the eligibility criteria for this study, they were classified as screen failures and could be considered for entry into another Novartis/Gyroscope sponsored study.

After providing the informed consent, subjects underwent ophthalmic and clinical assessments to determined eligibility for inclusion in the study.

Upon confirmation of eligibility, subjects were randomized to one of two dose groups (medium dose [5E10 vg] or high dose [2E11 vg]). Within each dose group, subjects were allocated to GT005, or untreated control based on a 2:1 ratio. The overall study population (N=approximately 250) aimed to include approximately 60% of subjects with foveal GA and 40% of subjects with non-foveal GA (extrafoveal lesions). The study eye was identified for all subjects.

Enrolment for HORIZON were composed of two stages. Stage 1 enrolled subjects with foveal or non-foveal GA until 180 subjects were randomized. Stage 2 enrolled subjects with nonfoveal GA. Subjects with a CFI rare variant associated with normal or low serum CFI were also allowed to be enrolled in Stage 2, irrespective of GA foveal involvement.

Subjects were stratified by GA lesion size on Fundus autofluorescence (FAF) (≤10 mm2 or >10 mm2) and AMD genotype subgroup. Randomization of study eyes in the GA lesion size upper stratum of >10 mm2 to 17.5 mm2 was capped at 20% of total subjects randomized in Stage 1 and Stage 2, respectively. In Stage 2, once enrolment capping at 20% based on upper GA lesion size was reached, eyes that fulfilled the cap criteria were no longer eligible, unless the subject had a CFI rare variant genotype (minor allele frequency ≤1%) previously associated with normal or low serum CFI or had an unreported CFI rare variant genotype (Group 1 and 5). A permuted-block method was used to obtain an approximately 2:1 ratio between GT005 and the untreated control groups for each dose group within each stratum.

Following randomization, the Investigator was informed of the subject's allocated treatment (GT005 or the untreated control group) and the study eye selected. To minimize bias during imaging grading, all imaging endpoint assessments and grading were performed at a Central reading centre (CRC). All imaging efficacy assessments were performed in a masked fashion. The Sponsor, subjects, investigators, and study personnel performing clinical assessments remained masked to the dose received for those allocated to GT005.

For each subject, the study comprised of a screening period lasting up to 8 weeks (or up to 12 weeks if agreed by the Sponsor Medical Monitor) followed by a 96-week study period. All subjects were assessed for the occurrence of AEs at each visit and underwent functional assessments, retinal imaging, and biological sampling as per the schedule of assessments.

This study was conducted in compliance with Independent ethics committees (IECs) / Institutional review boards (IRBs), informed consent regulations, the Declaration of Helsinki, International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) Guidelines, and the Food and Drug Administration (FDA), 21 Code of Federal Regulations (CFR) Part 11, Electronic Records, Electronic Signatures, and FDA, Guidance for Industry: Computerised Systems Used in Clinical Trials.

On 24-Aug-2023, the decision was taken to terminate the study and the GT005 program. The decision was aligned with the recommendation of an independent Data monitoring committee (DMC), which concluded that futility criteria had been met for the HORIZON study (GT005-03) and the overall benefit-risk ratio did not support continuation of the current development program as planned. All GT005- treated subjects, who were willing to be transferred into the long-term safety follow-up study were enrolled in the ORACLE (CPPY988A12203B) study.

02

Conditions studied

  • Dry Age-related Macular Degeneration

Keywords

  • Dry age-related macular degeneration
  • Geographic atrophy
  • Retinal disease
  • Eye disease
  • Retinal degeneration
  • Macular atrophy
03

Who can participate

Ages eligible
55 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
255 participants (actual)

Study arms

  • Experimental
    GT005 Medium dose [5E10 vg]

    GT005 Medium dose \[5E10 vg\]

    Drug: GT005

  • Experimental
    GT005 High dose [2E11 vg]

    GT005 High dose \[2E11 vg\]

    Drug: GT005

  • No intervention
    Untreated control

    Untreated control

Interventions

  • DrugGT005

    GT005 is a recombinant, non-replicating AAV2 expressing human complement factor I (CFI). GT005 was administered as a single time subretinal injection into the study eye of subjects allocated to one of the two GT005 doses.

05

What researchers measure

Primary outcomes

  1. The Change From Baseline to Week 72 in Geographic Atrophy (GA)

    GA area as measured by fundus autofluorescence (FAF)

    Time frame: Baseline, Weeks 12, 24, 36, 48 and 72

Secondary outcomes

  1. The Change From Baseline at Week 96 in Geographic Atrophy (GA)

    GA area as measured by fundus autofluorescence (FAF)

    Time frame: Baseline, Week 96

  2. Summary of Adverse Events

    An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject. A TEAE is defined as any AE that develops after randomization or any AE already present that worsens following randomization. The primary summaries of AEs are based on TEAEs.

    Time frame: Adverse events are reported from randomization to the end of study, at Week 96, up to a maximum timeframe of approximately 96 weeks.

  3. Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye

    An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject. A TEAE is defined as any AE that develops after randomization or any AE already present that worsens following randomization. The primary summaries of AEs are based on TEAEs. System organ classes are sorted alphabetically, and preferred terms are sorted by decreasing overall frequency within system organ class.

    Time frame: Adverse events are reported from randomization to the end of study, at Week 96, up to a maximum timeframe of approximately 96 weeks.

  4. Non-ocular AEs Occurring in ≥2% of Subjects

    An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject. A TEAE is defined as any AE that develops after randomization or any AE already present that worsens following randomization. The primary summaries of AEs are based on TEAEs.

    Time frame: Adverse events are reported from randomization to the end of study, at Week 96, up to a maximum timeframe of approximately 96 weeks.

  5. Change in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence

    Change in retinal morphology on multimodal imaging. For the untreated control group, there were no protocol-specified visits at Week 5.

    Time frame: Baseline, Weeks 5, 12, 24, 36, 48, 72 and 96

  6. Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart

    BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning. For the untreated control group, there were no protocol-specified visits for Weeks 1, 5 and 8.

    Time frame: Baseline, Weeks 1, 5, 8, 12, 24, 36, 48, 72 and 96

  7. Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, 48, 72 and 96, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart

    LLD was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. The test was to be performed after BCVA testing, prior to pupil dilation, and distance refraction was to be carried out before Low Luminance Visual Acuity (LLVA) was measured. LLVA was to be measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the subject read the normally illuminated ETDRS chart. The LLD was calculated as the difference between BCVA and LLVA. Initially, letters were to be read at a distance of 4 metres from the chart. If \<20 letters were read at 4 metres, testing at 1 metre should have been performed. LLD was to be reported as number of letters read correctly by the subject. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.

    Time frame: Baseline, Weeks 12, 24, 36, 48, 72 and 96

  8. Reading Performance, Measured as the MRS (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart: Summary Statistics for Change From Baseline by Visit for the Study Eye

    The maximum reading speed (MRS) represents the highest reading speed an individual can achieve when print size is not a limiting factor. Essentially, it measures how quickly a person can read text when the print is large enough to be easily readable. A higher count represents better visual functioning.

    Time frame: Baseline, Weeks 12, 24, 36, 48, 72 and 96

  9. Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index

    The FRI index is a patient-reported outcome measure developed specifically for use in GA patients. The FRI index evaluates the level of independence subjects have in performing everyday activities that require reading, such as writing a cheque or reading a prescription. Scores derived from the index range from 1 (unable to do) to 4 (total independence). A higher score represents better visual functioning.

    Time frame: Baseline, Weeks 24, 36, 48, 72 and 96

  10. Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score

    The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.

    Time frame: Baseline, Weeks 24, 36, 48, 72 and 96

06

Results

Posted Jul 10, 2025

Participant flow

This was a 3-arm study conducted in 2 stages. Results are reported per the 3 treatment arms. Stage 1 and Stage 2 results were combined since the study population and study treatments were the same in both Stage 1 and Stage 2; In Stage 1, participants were enrolled with both foveal and non-foveal geographic atrophy and in Stage 2, participants were enrolled with non-foveal geographic atrophy to enrich the number of participants with non-foveal geographic atrophy.

Participant flow — Overall Study
MilestoneGT005 Medium Dose [5E10 vg]GT005 High Dose [2E11 vg]Untreated Control
Started878682
Stage 1 (foveal and non-foveal geographic atrophy)646261
Stage 2 (non-foveal geographic atrophy)232421
Completed545135
Not completed333547
Withdrew: Death411
Withdrew: Lost to follow-up311
Withdrew: Study terminated by sponsor111732
Withdrew: Withdrawal by subject121413
Withdrew: Randomized but not treated due to ae210
Withdrew: Adverse event110

Outcome measures

PrimaryThe Change From Baseline to Week 72 in Geographic Atrophy (GA)

GA area as measured by fundus autofluorescence (FAF)

Time frame:
Baseline, Weeks 12, 24, 36, 48 and 72
Reported as:
Least squares mean · mm^2
The Change From Baseline to Week 72 in Geographic Atrophy (GA)
mm^2GT005 Medium Dose [5E10 vg]GT005 High Dose [2E11 vg]Untreated Control
Week 12 (n=75,71,72)0.730 ± 0.06250.752 ± 0.06340.667 ± 0.0647
Week 24 (n=72,75,71)1.151 ± 0.08331.260 ± 0.08311.054 ± 0.0860
Week 36 (n=66,66,71)1.728 ± 0.14881.955 ± 0.15031.531 ± 0.1528
Week 48 (n=64,68,65)2.098 ± 0.18412.535 ± 0.18532.047 ± 0.1896
Week 72 (n=56,51,54)3.225 ± 0.23373.421 ± 0.23692.919 ± 0.2412
Statistical analysis
  • GT005 Medium Dose [5E10 vg] vs Untreated Control · mixed model repeated measures · Ls mean difference: 0.062 · 90% CI -0.087 to 0.211
  • GT005 High Dose [2E11 vg] vs Untreated Control · mixed model repeated measures · Ls mean difference: 0.084 · 90% CI -0.066 to 0.234
  • GT005 Medium Dose [5E10 vg] vs Untreated Control · mixed model repeated measures · Ls mean difference: 0.096 · 90% CI -0.102 to 0.294
  • GT005 High Dose [2E11 vg] vs Untreated Control · mixed model repeated measures · Ls mean difference: 0.205 · 90% CI 0.007 to 0.404
  • GT005 Medium Dose [5E10 vg] vs Untreated Control · mixed model repeated measures · Ls mean difference: 0.197 · 90% CI -0.155 to 0.550
  • GT005 High Dose [2E11 vg] vs Untreated Control · mixed model repeated measures · Ls mean difference: 0.423 · 90% CI 0.068 to 0.779
  • GT005 Medium Dose [5E10 vg] vs Untreated Control · mixed model repeated measures · Ls mean difference: 0.052 · 90% CI -0.385 to 0.489
  • GT005 High Dose [2E11 vg] vs Untreated Control · mixed model repeated measures · Ls mean difference: 0.488 · 90% CI 0.049 to 0.928
  • GT005 Medium Dose [5E10 vg] vs Untreated Control · mixed model repeated measures · Ls mean difference: 0.307 · 90% CI -0.248 to 0.862
  • GT005 High Dose [2E11 vg] vs Untreated Control · mixed model repeated measures · Ls mean difference: 0.503 · 90% CI -0.058 to 1.063
SecondaryThe Change From Baseline at Week 96 in Geographic Atrophy (GA)

GA area as measured by fundus autofluorescence (FAF)

Time frame:
Baseline, Week 96
Reported as:
Least squares mean · mm2
The Change From Baseline at Week 96 in Geographic Atrophy (GA)
mm2GT005 Medium Dose [5E10 vg]GT005 High Dose [2E11 vg]Untreated Control
The Change From Baseline at Week 96 in Geographic Atrophy (GA)4.414 ± 0.31094.607 ± 0.31673.769 ± 0.3286
Statistical analysis
  • GT005 Medium Dose [5E10 vg] vs Untreated Control · mixed model repeated measures · Ls mean difference: 0.645 · 90% CI -0.103 to 1.393
  • GT005 High Dose [2E11 vg] vs Untreated Control · mixed model repeated measures · Ls mean difference: 0.838 · 90% CI 0.081 to 1.594
SecondarySummary of Adverse Events

An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject. A TEAE is defined as any AE that develops after randomization or any AE already present that worsens following randomization. The primary summaries of AEs are based on TEAEs.

Time frame:
Adverse events are reported from randomization to the end of study, at Week 96, up to a maximum timeframe of approximately 96 weeks.
Reported as:
Count of participants · Participants
Summary of Adverse Events
ParticipantsGT005 Medium Dose [5E10 vg]GT005 High Dose [2E11 vg]Untreated Control
Subjects with at least one ocular adverse event for the study eye666515
Subjects with at least one ocular adverse event for the fellow eye323514
Subjects with at least one non-ocular adverse event635944
Subjects with at least one ocular adverse event related to study treatment for the study eye13210
Subjects with at least one non-ocular adverse event related to study treatment000
Subjects with at least one ocular adverse event related to surgical procedure for the study eye48480
Subjects with at least one non-ocular adverse event related to surgical procedure000
Subjects with at least one ocular adverse event related to study procedure for the study eye890
Subjects with at least one non-ocular adverse event related to study procedure020
Subjects with at least one ocular adverse event leading to study discontinuation for the study eye000
Subjects with at least one non-ocular adverse event leading to study discontinuation521
Subjects with at least one ocular adverse event of special interest for the study eye19313
Subjects with at least one ocular adverse event of special interest for the fellow eye331
Subjects with at least one ocular serious adverse event (SAE) for the study eye250
Subjects with at least one ocular serious adverse event for the fellow eye000
Subjects with at least one non-ocular serious adverse event202210
Subjects with at least one ocular serious adverse event related to study treatment for the study eye000
Subjects with at least one non-ocular serious adverse event related to study treatment000
Subjects with at least one ocular SAE related to surgical procedure for the study eye140
Subjects with at least one non-ocular serious adverse event related to surgical procedure000
Subjects with at least one ocular serious adverse event related to study procedure for the study eye110
Subjects with at least one non-ocular serious adverse event related to study procedure000
Subjects with at least one ocular SAE leading to study discontinuation for the study eye000
Subjects with at least one non-ocular serious adverse event leading to study discontinuation521
Deaths411
SecondaryOcular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye

An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject. A TEAE is defined as any AE that develops after randomization or any AE already present that worsens following randomization. The primary summaries of AEs are based on TEAEs. System organ classes are sorted alphabetically, and preferred terms are sorted by decreasing overall frequency within system organ class.

Time frame:
Adverse events are reported from randomization to the end of study, at Week 96, up to a maximum timeframe of approximately 96 weeks.
Reported as:
Count of participants · Participants
Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye
ParticipantsGT005 Medium Dose [5E10 vg]GT005 High Dose [2E11 vg]Untreated Control
Subjects with at least one event666515
Eye disorders656214
-Cataract21203
-Retinal pigmentation12220
-Conjunctival haemorrhage18121
-Retinal haemorrhage8102
-Eye pain570
-Ocular hypertension660
-Punctate keratitis660
-Retinal tear560
-Dry eye441
-Posterior capsule opacification342
-Anterior chamber cell440
-Eye irritation620
-Vitreous haemorrhage260
-Choroidal neovascularisation232
-Vitreous floaters340
-Cataract nuclear330
-Retinal detachment240
-Corneal oedema140
-Diplopia410
-Eye pruritus140
-Foreign body sensation in eyes320
-Iritis410
-Visual impairment230
Investigations1120
-Intraocular pressure increased120
SecondaryNon-ocular AEs Occurring in ≥2% of Subjects

An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject. A TEAE is defined as any AE that develops after randomization or any AE already present that worsens following randomization. The primary summaries of AEs are based on TEAEs.

Time frame:
Adverse events are reported from randomization to the end of study, at Week 96, up to a maximum timeframe of approximately 96 weeks.
Reported as:
Count of participants · Participants
Non-ocular AEs Occurring in ≥2% of Subjects
ParticipantsGT005 Medium Dose [5E10 vg]GT005 High Dose [2E11 vg]Untreated Control
Non-ocular AEs Occurring in ≥2% of Subjects635944
SecondaryChange in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence

Change in retinal morphology on multimodal imaging. For the untreated control group, there were no protocol-specified visits at Week 5.

Time frame:
Baseline, Weeks 5, 12, 24, 36, 48, 72 and 96
Reported as:
Count of participants · Participants
Change in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence
ParticipantsGT005 Medium Dose [5E10 vg]GT005 High Dose [2E11 vg]Untreated Control
Week 5 (n=23,24,0)2323—
Week 12 (n=75,73,74)747373
Week 24 (n=75,78,72)727871
Week 36 (n=70,70, 71)666970
Week 48 (n=67,72,68)677168
Week 72 (n=61, 62,59)606056
Week 96 (n=52,49, 34)504833
SecondaryChange in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart

BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning. For the untreated control group, there were no protocol-specified visits for Weeks 1, 5 and 8.

Time frame:
Baseline, Weeks 1, 5, 8, 12, 24, 36, 48, 72 and 96
Reported as:
Least squares mean · Letters read
Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart
Letters readGT005 Medium Dose [5E10 vg]GT005 High Dose [2E11 vg]Untreated Control
Week 1 (n=81,78,0)-2.0 ± 1.54-7.0 ± 1.56—
Week 5 (n=81,78,0)-0.8 ± 0.88-3.3 ± 0.89—
Week 8 (n=79,77,0)-0.1 ± 0.85-1.7 ± 0.86—
Week 12 (n=79,79,73)-1.1 ± 0.91-2.5 ± 0.91-0.7 ± 0.96
Week 24 (n=78,78,71)-2.7 ± 1.03-6.3 ± 1.03-1.1 ± 1.09
Week 36 (75,74,72)-2.5 ± 1.24-7.7 ± 1.25-3.0 ± 1.30
Week 48 (n=73,75,69)-2.6 ± 1.48-7.3 ± 1.46-5.3 ± 1.54
Week 72 (n=63, 70, 58)-4.1 ± 1.54-7.9 ± 1.50-8.8 ± 1.61
Week 96 (n=54,51,35)-5.5 ± 1.78-10.0 ± 1.78-12.7 ± 2.02
Statistical analysis
  • GT005 Medium Dose [5E10 vg] vs Untreated Control · mixed model repeated measures · Ls mean difference: -0.5 · 90% CI -2.6 to 1.7
  • GT005 High Dose [2E11 vg] vs Untreated Control · mixed model repeated measures · Ls mean difference: -1.8 · 90% CI -4.0 to 0.4
  • GT005 Medium Dose [5E10 vg] vs Untreated Control · mixed model repeated measures · Ls mean difference: -1.6 · 90% CI -4.1 to 0.8
  • GT005 High Dose [2E11 vg] vs Untreated Control · mixed model repeated measures · Ls mean difference: -5.3 · 90% CI -7.7 to -2.8
  • GT005 Medium Dose [5E10 vg] vs Untreated Control · mixed model repeated measures · Ls mean difference: 0.5 · 90% CI -2.5 to 3.5
  • GT005 High Dose [2E11 vg] vs Untreated Control · mixed model repeated measures · Ls mean difference: -4.7 · 90% CI -7.7 to -1.7
  • GT005 Medium Dose [5E10 vg] vs Untreated Control · mixed model repeated measures · Ls mean difference: 2.6 · 90% CI -0.9 to 6.1
  • GT005 High Dose [2E11 vg] vs Untreated Control · mixed model repeated measures · Ls mean difference: -2.1 · 90% CI -5.6 to 1.4
  • GT005 Medium Dose [5E10 vg] vs Untreated Control · mixed model repeated measures · Ls mean difference: 4.7 · 90% CI 1.0 to 8.4
  • GT005 High Dose [2E11 vg] vs Untreated Control · mixed model repeated measures · Ls mean difference: 0.9 · 90% CI -2.8 to 4.5
  • GT005 Medium Dose [5E10 vg] vs Untreated Control · mixed model repeated measures · Ls mean difference: 7.1 · 90% CI 2.7 to 11.6
  • GT005 High Dose [2E11 vg] vs Untreated Control · mixed model repeated measures · Ls mean difference: 2.6 · 90% CI -1.8 to 7.1
SecondaryChange in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, 48, 72 and 96, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart

LLD was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. The test was to be performed after BCVA testing, prior to pupil dilation, and distance refraction was to be carried out before Low Luminance Visual Acuity (LLVA) was measured. LLVA was to be measured by placing a 2.0-log-unit neutral density filter over the front of each eye and having the subject read the normally illuminated ETDRS chart. The LLD was calculated as the difference between BCVA and LLVA. Initially, letters were to be read at a distance of 4 metres from the chart. If \<20 letters were read at 4 metres, testing at 1 metre should have been performed. LLD was to be reported as number of letters read correctly by the subject. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.

Time frame:
Baseline, Weeks 12, 24, 36, 48, 72 and 96
Reported as:
Mean · Letters read
Change in Low Luminance Difference (LLD) Letter Count From Baseline at Weeks 12, 24, 36, 48, 72 and 96, Via Early Treatment for Diabetic Retinopathy (ETDRS) Chart
Letters readGT005 Medium Dose [5E10 vg]GT005 High Dose [2E11 vg]Untreated Control
Week 12-0.6 ± 7.59-1.1 ± 9.631.2 ± 9.51
Week 24 (n=78,75,71)-0.6 ± 10.10-2.5 ± 12.730.5 ± 12.01
Week 36 (n=75,72,71)0.0 ± 9.90-2.6 ± 13.40-0.1 ± 11.12
Week 48 (n=73,73,69)-0.5 ± 10.31-1.5 ± 15.18-0.4 ± 12.93
Week 72 (n=63,67,58)-0.5 ± 13.15-5.2 ± 17.24-2.5 ± 14.93
Week 96 (n=54,49,35)-3.1 ± 16.11-2.2 ± 13.48-5.9 ± 16.82
SecondaryReading Performance, Measured as the MRS (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart: Summary Statistics for Change From Baseline by Visit for the Study Eye

The maximum reading speed (MRS) represents the highest reading speed an individual can achieve when print size is not a limiting factor. Essentially, it measures how quickly a person can read text when the print is large enough to be easily readable. A higher count represents better visual functioning.

Time frame:
Baseline, Weeks 12, 24, 36, 48, 72 and 96
Reported as:
Mean · Words read per minute
Reading Performance, Measured as the MRS (Words Per Minute), as Assessed by Minnesota Low-vision Reading Test (MNRead) Chart: Summary Statistics for Change From Baseline by Visit for the Study Eye
Words read per minuteGT005 Medium Dose [5E10 vg]GT005 High Dose [2E11 vg]Untreated Control
Week 24 (n=73,72,65)-15.756 ± 32.7268-12.368 ± 43.2054-15.769 ± 40.5051
Week 36 (n=71,70,65)-18.488 ± 54.7913-15.673 ± 31.7802-3.689 ± 94.1057
Week 48 (n=69,67,62)-20.734 ± 36.4110-6.678 ± 49.0844-17.297 ± 56.8547
Week 72 (n=57,64,53)-24.485 ± 45.8525-20.798 ± 39.6796-26.121 ± 40.8016
Week 96 (n=48,47,29)-24.678 ± 44.7777-25.178 ± 39.7216-19.242 ± 45.0703
SecondaryChange From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index

The FRI index is a patient-reported outcome measure developed specifically for use in GA patients. The FRI index evaluates the level of independence subjects have in performing everyday activities that require reading, such as writing a cheque or reading a prescription. Scores derived from the index range from 1 (unable to do) to 4 (total independence). A higher score represents better visual functioning.

Time frame:
Baseline, Weeks 24, 36, 48, 72 and 96
Reported as:
Mean · Scores on a scale
Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index
Scores on a scaleGT005 Medium Dose [5E10 vg]GT005 High Dose [2E11 vg]Untreated Control
Week 24 (n=77,75,67)-0.4 ± 5.20-1.4 ± 4.74-0.1 ± 3.98
Week 36 (n=74,72,66)-0.8 ± 4.64-1.1 ± 4.31-0.1 ± 4.67
Week 48 (n=70,73,65)-0.3 ± 4.76-1.4 ± 4.87-0.2 ± 4.50
Week 72 (n=63,69,58)-0.8 ± 4.93-1.3 ± 5.19-1.5 ± 5.37
Week 96 (n=54,51,32)-1.4 ± 5.57-1.4 ± 4.41-1.1 ± 5.11
SecondaryChange From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score

The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.

Time frame:
Baseline, Weeks 24, 36, 48, 72 and 96
Reported as:
Mean · Scores on a scale
Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score
Scores on a scaleGT005 Medium Dose [5E10 vg]GT005 High Dose [2E11 vg]Untreated Control
Week 24 (n=77,78,67)-1.466 ± 12.8742-2.289 ± 12.3295-1.270 ± 11.2063
Week 36 (n=74,73,66)-1.955 ± 11.5060-3.479 ± 12.0848-2.273 ± 12.2395
Week 48 (n=70,74,65)-2.501 ± 12.9563-3.113 ± 11.9974-4.403 ± 14.2465
Week 72 (n=63,69,54)-4.232 ± 14.6259-3.432 ± 11.3840-6.583 ± 15.5133
Week 96 (n=54,51,33)-6.341 ± 14.4187-7.718 ± 10.9016-6.804 ± 15.4812

Adverse events

Collected over Adverse events are reported from randomization to the end of study, at Week 96, up to a maximum timeframe of approximately 96 weeks.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
GT005@Medium Dose@[5E10 vg]4/87 (4.6%)22/87 (25.3%)76/87 (87.4%)
GT005@High Dose@[2E11 vg]1/86 (1.2%)25/86 (29.1%)75/86 (87.2%)
Untreated Control1/82 (1.2%)10/82 (12.2%)50/82 (61%)
Overall6/255 (2.4%)57/255 (22.4%)201/255 (78.8%)
Most frequent serious events
Showing 10 of 75
Most frequent serious events
EventGT005@Medium Dose@[5E10 vg]GT005@High Dose@[2E11 vg]Untreated ControlOverall
Endophthalmitis - Study eyeInfections and infestations0/873/860/823/255
Atrial fibrillationCardiac disorders3/871/860/824/255
Cardiac failure congestiveCardiac disorders0/872/860/822/255
Retinal detachment - Study eyeEye disorders1/872/860/823/255
SepsisInfections and infestations1/872/860/823/255
Acute kidney injuryRenal and urinary disorders0/872/861/823/255
Hip fractureInjury, poisoning and procedural complications2/870/861/823/255
SyncopeNervous system disorders2/871/860/823/255
Angina pectorisCardiac disorders1/870/861/822/255
BradycardiaCardiac disorders0/870/861/821/255
Most frequent other events
Showing 10 of 440
Most frequent other events
EventGT005@Medium Dose@[5E10 vg]GT005@High Dose@[2E11 vg]Untreated ControlOverall
Retinal pigmentation - Study eyeEye disorders12/8722/860/8234/255
Cataract - Study eyeEye disorders21/8720/863/8244/255
Conjunctival haemorrhage - Study eyeEye disorders18/8712/861/8231/255
COVID-19Infections and infestations14/8712/869/8235/255
Intraocular pressure increased - Study eyeInvestigations11/872/860/8213/255
Cataract - Fellow eyeEye disorders5/8710/862/8217/255
Retinal haemorrhage - Study eyeEye disorders8/8710/862/8220/255
Eye pain - Study eyeEye disorders5/877/860/8212/255
Urinary tract infectionInfections and infestations7/873/863/8213/255
Ocular hypertension - Study eyeEye disorders6/876/860/8212/255

Baseline characteristics

Age, Continuous
Age, Continuous(Years)GT005 Medium Dose [5E10 vg]GT005 High Dose [2E11 vg]Untreated ControlTotal
Mean77.6 ± 7.3377.6 ± 7.6077.8 ± 6.8377.7 ± 7.24
Sex: Female, Male
Sex: Female, Male(Participants)GT005 Medium Dose [5E10 vg]GT005 High Dose [2E11 vg]Untreated ControlTotal
Female526153166
Male35252989
Race (NIH/OMB)
Race (NIH/OMB)(Participants)GT005 Medium Dose [5E10 vg]GT005 High Dose [2E11 vg]Untreated ControlTotal
American Indian or Alaska Native0000
Asian0101
Native Hawaiian or Other Pacific Islander0000
Black or African American0000
White878080247
More than one race0000
Unknown or Not Reported0527
07

Study locations

62 sites
  • Retinal Research Institute (retina consultants of AZ)
    Phoenix, Arizona 85053, United States
  • Retina Vitreous Associates Medical Group
    Beverly Hills, California 90211, United States
  • Retina Consultants of Orange County
    Fullerton, California 92835, United States
  • Northern California Retina Vitreous Associates
    Mountain View, California 94040, United States
  • Byers Eye Institute at Stanford
    Palo Alto, California 94303, United States
  • Retina Consultants of San Diego
    Poway, California 92064, United States
  • University of California (UC) Davis Medical Group Eye Center
    Sacramento, California 95817, United States
  • Southwest Retina Research Center
    Durango, Colorado 81303, United States
  • Rand Eye Institute
    Deerfield Beach, Florida 33064, United States
  • VitreoRetinal Associates, P.A.
    Gainesville, Florida 32607, United States
  • Bascom Palmer Eye Institute
    Miami, Florida 33136, United States
  • Retina Vitreous Associates of Florida
    St. Petersburg, Florida 33711, United States
  • Southeast Retina Center
    Augusta, Georgia 30909, United States
  • Georgia Retina PC
    Marietta, Georgia 30060, United States
  • Illinois Retina Associates
    Chicago, Illinois 60657, United States
  • University Retina Macula Associates PC
    Lemont, Illinois 60452, United States
  • Midwest Eye Institute Northside
    Indianapolis, Indiana 46290, United States
  • Wolfe Eye Clinic
    West Des Moines, Iowa 50266, United States
  • Retina Associates, LLC
    Shawnee Mission, Kansas 66204, United States
  • The Retina Care Center
    Baltimore, Maryland 21209, United States
  • Ophthalamic Consultants of Boston (OCB)
    Boston, Massachusetts 02114, United States
  • Retina Associates of Michigan
    Grand Blanc, Michigan 48439, United States
  • Associated Retinal Consultants PC
    Royal Oak, Michigan 48073, United States
  • Sierra Eye Associates
    Reno, Nevada 89502, United States
  • Columbia University Medical Center
    New York, New York 10032, United States
  • Retina Associates of Western New York
    Rochester, New York 14620, United States
  • Duke Eye Center
    Durham, North Carolina 27705, United States
  • Cincinnati Eye Institute
    Cincinnati, Ohio 45242, United States
  • Cleveland Clinic
    Cleveland, Ohio 44195, United States
  • Oregon Retina
    Eugene, Oregon 97401, United States
  • Casey Eye Institute - OHSU
    Portland, Oregon 97239, United States
  • Erie Retinal Surgery ,INC
    Erie, Pennsylvania 16507, United States
  • Mid Atlantic Retina - Wills Eye Hospital
    Philadelphia, Pennsylvania 19107, United States
  • Palmetto Retina Center
    West Columbia, South Carolina 29169, United States
  • Charles Retina Institute
    Germantown, Tennessee 38138, United States
  • Southeastern Retina Associates, PC
    Knoxville, Tennessee 37922, United States
  • Austin Research Center for Retina, PLLC
    Austin, Texas 78705, United States
  • Retina Consultants of Houston-TMC
    Bellaire, Texas 77401, United States
  • Retina Foundation of the Southwest
    Dallas, Texas 75231, United States
  • Texas Retina Associates (Dallas)
    Dallas, Texas 75231, United States
  • Retinal Consultants of San Antonio
    San Antonio, Texas 78240, United States
  • Retina Consultants of Houston
    The Woodlands, Texas 77384, United States
  • Rocky Mountain Retina Consultants
    Salt Lake City, Utah 84107, United States
  • Department of Ophthalmology UW Medicine
    Seattle, Washington 98104-2499, United States
  • Retina Center Northwest
    Silverdale, Washington 98383, United States
  • Sydney Hospital and Sydney Eye Hospital
    Sydney, New South Wales 2000, Australia
  • The University of Melbourne - The Centre for Eye Research Australia (CERA)
    Melbourne E., Victoria 3002, Australia
  • CHU Dijon - Hopital Mitterrand
    Dijon, 21000, France
  • Centre Paradis Monticelli
    Marseille, 13008, France
  • CHU de Nantes - Hôtel-Dieu
    Nantes, 44093, France
  • Universitätsklinikum Bonn
    Bonn, 53127, Germany
  • Internationale Innovative Ophthalmochirurgie
    Düsseldorf, 40549, Germany
  • Universitaetsklinikum Schleswig-Holstein - Campus Lübeck
    Lübeck, 23562, Germany
  • Universitaetsklinikum Tuebingen
    Tübingen, 72076, Germany
  • Oftalmika Spolka z ograniczona odpowiedzialnoscia
    Bydgoszcz, 85-631, Poland
  • Instituto de microcirugía ocular
    Barcelona, 08035, Spain
  • Clinica Baviera
    Madrid, 28046, Spain
  • Clinica Universidad de Navarra - Pamplona
    Pamplona, 31008, Spain
  • Moorfields Eye Hospital - NHS Foundation Trust
    London, EC1V 2PD, United Kingdom
  • Retina Clinic London
    London, W1G 7LB, United Kingdom
  • John Radcliffe Hospital
    Oxford, OX3 9DU, United Kingdom
  • Sunderland Eye Infirmary
    Sunderland, SR2 9HP, United Kingdom
08

References and documents

Publications

  • Tzoumas N, Riding G, Williams MA, Steel DH. Complement inhibitors for age-related macular degeneration. Cochrane Database Syst Rev. 2023 Jun 14;6(6):CD009300. doi: 10.1002/14651858.CD009300.pub3. PubMed 37314061 ↗

Study documents

  • Study protocol · Sep 15, 2022
  • Statistical analysis plan · Jun 13, 2024

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT04566445
Lead sponsor
Gyroscope Therapeutics Limited
Collaborators
Novartis Pharmaceuticals
Responsible party
Sponsor
First posted
Sep 28, 2020
Start date
Sep 28, 2020
Primary completion
Jun 10, 2024
Completion
Jun 10, 2024
Results posted
Jul 10, 2025
Last update
Jan 28, 2026

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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