Prospective, Randomised, Placebo-controlled, Double-masked, Three-armed Multi-centre Trial of Aganirsen Versus Vehicle in Patients After Ischaemic Central Retinal Vein Occlusion With a High Risk to Develop Neovascular Glaucoma
试验速览
- 阶段
- 2 期
- 入组人数
- 333
- 主要终点
- NVG component
研究概览
简要总结
A prospective, randomised, placebo-controlled, double-masked, three-armed multi-centre phase II/III trial for the Study of a Topical Treatment of Ischaemic Central Retinal Vein Occlusion to Prevent Neovascular Glaucoma - the STRONG Study
详细描述
The STRONG Study is a phase II/III prospective, randomised, placebo-controlled, double-masked, three-armed multi-centre study of aganirsen antisense oligonucleotide, a topical treatment for iCRVO intended to prevent Neovascular Glaucoma (NVG). The study will evaluate the efficacy of two different doses of aganirsen formulated in an eye emulsion in avoiding new vessel formation by blocking the Insulin Receptor Substrate (IRS)-1. Eligible patients will be treated with aganirsen or placebo for a period of 24 weeks. They will also be invited to participate in sub-studies working on the analysis of gonioscopic images, detection of biomarkers for neovascular glaucoma and risk factors for ischaemic central retinal vein occlusion.
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)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects meeting all of the following criteria will be considered for enrolment to the trial:
- •Male or female ≥ 18 years
- •IOP in the study eye ≤ 21mmHg
- •Primary ischaemic CRVO or conversion to ischaemic CRVO in the study eye for no longer than 4 weeks
- •Best-corrected visual acuity (BCVA) ETDRS letter score < 35 (< 20/200 Snellen equivalent) in the study eye
- •≥ 10-disc area of retinal capillary obliteration on fluorescein fundus angiography in the study eye (central fundus: macular area as defined by the optic disc and the arcades, an approximate 6000 micron circle around the fovea) and/or large, confluent retinal haemorrhages in the study eye
- •Must be accompanied by 4 or more out of 6 following criteria:
- •A relative afferent pupillary defect (with a normal fellow eye)
- •≥ 10 cotton-wool-spots in the study eye
- •Venous tortuosity in the study eye
- •Peripheral visual field defects corresponding to ischaemia (Goldmann perimeter or other semi-automatic kinetic methods) in the study eye
- •Engorged vessels on iris and/or in the chamber angle in the study eye
- •Detectable anterior chamber flare in the study eye
排除标准
- •Subjects presenting 1 or more of the following criteria will not be enrolled in the trial:
- •Ocular conditions with a poorer prognosis in the fellow eye than in the study eye
- •Primary or secondary glaucoma in the study eye
- •Prior or concomitant ocular treatment with anti-VEGF in the study eye (ranibizumab/bevacizumab is not allowed within the last 45 days, aflibercept within the last 90 days) before screening visit
- •Use of anti-VEGF treatment in the fellow eye during the trial
- •Previous use of intraocular corticosteroids at any time or use of periocular corticosteroids in the study eye within 90 days prior to screening visit
- •History of idiopathic or autoimmune uveitis in either eye
- •Presence of NVD, NVE or anterior segment neovascularisation (NVA or NVI) in the study eye
- •Previous PRP in the study eye
- •Intraocular surgery (other than intravitreal anti-VEGF treatment) or laser treatment in the study eye within the past 90 days before screening visit
- •Patients with a history of breast cancer
研究组 & 干预措施
aganirsen "low-dose":
43µg daily, one drop of 0.86 mg/g emulsion (morning) + one drop of placebo (evening) daily
干预措施: aganirsen (Drug)
aganirsen "high-dose"
86µg daily, one drop of 0.86 mg/g emulsion twice daily (morning and evening)
干预措施: aganirsen (Drug)
aganirsen placebo (vehicle)
one drop of placebo emulsion (morning) + one drop of placebo emulsion (evening) daily
干预措施: aganirsen (Drug)
结局指标
主要结局
NVG component
时间窗: Week 24
Co-primary I: NVG component scored dichotomously (NVG=yes/NVG=no) where "yes" is development of NVI, NVA, NVD, and/or NVE, or rescue treatment; "no" otherwise
IOP component
时间窗: Week 24
Co-primary II: IOP component scored dichotomously (failure/success); "failure" is rise in IOP from baseline to week 24 of ≥ 20% to \> 21 or rescue treatment; "success" otherwise
次要结局
- Secondary NVG(24 weeks)
- Required intensity of laser spots of additional laser treatments and re-treatments in the study eye at up to week 24(24 weeks)
- Retinal Thickness(24 weeks)
- Anterior segment neovascularisation(24 weeks)
- NVG Classification(24 weeks)
- Number of additional needed laser treatments and re-treatments in the study eye at up to week 24(24 weeks)
- Retinal non-perfusion area(24 weeks)
- Visual Acuity(24 weeks)
- Quality of Life(24 weeks)
- Quality of Life on EQ-5D(24 weeks)
- Safety: Incidence of treatment-emergent Adverse Events(24 weeks)