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
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 255
- 试验地点
- 62
- 主要终点
- The Change From Baseline to Week 72 in Geographic Atrophy (GA)
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 55 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able and willing to give written informed consent
- •Age ≥55 years
- •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)
- •GA lesion(s) within an acceptable size on FAF, in the study eye
- •The GA lesion in the study eye must reside completely within the FAF image
- •Up to 25% of the enrolled study population are permitted to have CNV in the fellow eye
- •Have a BCVA of ≥24 letters (6/95 or 20/320 Snellen acuity equivalent), using ETDRS charts, in the study eye
- •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
- •Able to attend all study visits and complete the study procedures
- •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
排除标准
- •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
- •Have a history, or evidence, of CNV in the study eye
- •Presence of moderate/severe or worse non-proliferative, diabetic retinopathy in the study eye
- •Have history of vitrectomy, sub-macular surgery, or macular photocoagulation in the study eye
- •History of intraocular surgery in the study eye within 12 weeks prior to Visit 1
- •Have clinically significant cataract that may require surgery during the study period in the study eye
- •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
- •Axial myopia of greater than -8 diopters in the study eye
- •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
- •Have received a gene or cell therapy at any time.
- •Have a contraindication to the protocol specified corticosteroid regimen
- •Are unwilling to use two forms of contraception (one of which being a barrier method) for 90 days post-dosing, if relevant
- •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
- •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
研究组 & 干预措施
GT005 Medium dose [5E10 vg]
GT005 Medium dose [5E10 vg]
干预措施: GT005 (Drug)
GT005 High dose [2E11 vg]
GT005 High dose [2E11 vg]
干预措施: GT005 (Drug)
Untreated control
Untreated control
结局指标
主要结局
The Change From Baseline to Week 72 in Geographic Atrophy (GA)
时间窗: Baseline, Weeks 12, 24, 36, 48 and 72
GA area as measured by fundus autofluorescence (FAF)
次要结局
- The Change From Baseline at Week 96 in Geographic Atrophy (GA)(Baseline, Week 96)
- Summary of Adverse Events(Adverse events are reported from randomization to the end of study, at Week 96, up to a maximum timeframe of approximately 96 weeks.)
- Ocular AEs Occurring in ≥2% of Subjects by Primary System Organ Class and Preferred Term for the Study Eye(Adverse events are reported from randomization to the end of study, at Week 96, up to a maximum timeframe of approximately 96 weeks.)
- Non-ocular AEs Occurring in ≥2% of Subjects(Adverse events are reported from randomization to the end of study, at Week 96, up to a maximum timeframe of approximately 96 weeks.)
- Change in GA Morphology From Baseline to Week 96 on Multimodal Imaging - Number of Participants With Increase in Fundus Autofluorescence(Baseline, Weeks 5, 12, 24, 36, 48, 72 and 96)
- Change in Best Corrected Visual Acuity (BCVA) Score From Baseline Through Week 96 Via the Early Treatment for Diabetic Retinopathy (ETDRS) Chart(Baseline, Weeks 1, 5, 8, 12, 24, 36, 48, 72 and 96)
- 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(Baseline, Weeks 12, 24, 36, 48, 72 and 96)
- 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(Baseline, Weeks 12, 24, 36, 48, 72 and 96)
- Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Functional Reading Independence (FRI) Index(Baseline, Weeks 24, 36, 48, 72 and 96)
- Change From Baseline at Weeks 24, 36, 48, 72 and 96 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Composite Score(Baseline, Weeks 24, 36, 48, 72 and 96)