Clinical trial NCT02947867: Trial of Aganirsen in iCRVO Patients at Risk of Developing NVG
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Ischaemic Central Retinal Vein Occlusion
Neovascular Glaucoma
Lead sponsor: Gene Signal SAS
Sponsor class: INDUSTRY
Collaborators: name: Johannes Gutenberg University Mainz
name: University Hospital of Cologne
name: Moorfields Eye Hospital NHS Foundation Trust
First posted: 2016-10-28
Enrollment: 333
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

Primary outcomes:
measure: NVG component
timeFrame: Week 24
measure: IOP component
timeFrame: Week 24
Secondary outcomes:
measure: Secondary NVG
timeFrame: 24 weeks
measure: Anterior segment neovascularisation
timeFrame: 24 weeks
measure: NVG Classification
timeFrame: 24 weeks
measure: Visual Acuity
timeFrame: 24 weeks
measure: Number of additional needed laser treatments and re-treatments in the study eye at up to week 24
timeFrame: 24 weeks
measure: Required intensity of laser spots of additional laser treatments and re-treatments in the study eye at up to week 24
timeFrame: 24 weeks
measure: Retinal non-perfusion area
timeFrame: 24 weeks
measure: Retinal Thickness
timeFrame: 24 weeks
measure: Quality of Life
timeFrame: 24 weeks
measure: Quality of Life on EQ-5D
timeFrame: 24 weeks
measure: Safety: Incidence of treatment-emergent Adverse Events
timeFrame: 24 weeks
Other outcomes:
Locations:
Study officials:
References:
citation: Lorenz K, Scheller Y, Bell K, Grus F, Ponto KA, Bock F, Cursiefen C, Flach J, Gehring M, Peto T, Silva R, Tal Y, Pfeiffer N. A prospective, randomised, placebo-controlled, double-masked, three-armed, multicentre phase II/III trial for the Study of a Topical Treatment of Ischaemic Central Retinal Vein Occlusion to Prevent Neovascular Glaucoma - the STRONG study: study protocol for a randomised controlled trial. Trials. 2017 Mar 16;18(1):128. doi: 10.1186/s13063-017-1861-3.