Trial of Aganirsen in iCRVO Patients at Risk of Developing NVG

Neovascular Glaucoma Clinical Trial

— STRONG  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02947867
• Other study ID #: GS-101-P1-NVR
• Secondary ID: 2014-000239-18
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• First received: October 15, 2016
• Last updated: October 28, 2016
• Start date: January 2017
• Est. completion date: December 2019

Study information

• Verified date: October 2016
• Source: Gene Signal SAS
• Contact: Katrin Lorenz, MD
• Phone: +49613117
• Email: katrin.lorenz[@]unimedizin-mainz.de
• Is FDA regulated: No
• Health authority: European Union: European Medicines Agency
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 333
• Est. completion date: December 2019
• Est. primary completion date: June 2019
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glaucoma
• Glaucoma, Neovascular
• Ischaemic Central Retinal Vein Occlusion
• Ischemia
• Neovascular Glaucoma
• Retinal Vein Occlusion

Intervention

Drug:
• aganirsen
aganirsen antisense oligonucleotide against Insulin Receptor Substrate (IRS-1)

Locations

Country	Name	City	State
n/a

Sponsors (4)

Lead Sponsor	Collaborator
Gene Signal SAS	Johannes Gutenberg University Mainz, Moorfields Eye Hospital NHS Foundation Trust, University Hospital of Cologne

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	NVG component	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	Week 24	No
Primary	IOP component	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	Week 24	No
Secondary	Secondary NVG	The time to development of secondary NVG in the study eye up to week 24 (in case aganirsen does not totally inhibit but slows down the development of NVG).	24 weeks	No
Secondary	Anterior segment neovascularisation	The time to development of anterior segment neovascularisation (NVI or NVA), NVD or NVE in the study eye, requiring PRP or cryotherapy up to week 24.	24 weeks	No
Secondary	NVG Classification	NVG Classification at 24 weeks on a scale from 1 (non-NVG) to 6 (most advanced NVG) based on central reading of neovascularisation	24 weeks	No
Secondary	Visual Acuity	The change from baseline in BCVA (EDTRS letter score) in the study eye to week 24.	24 weeks	Yes
Secondary	Number of additional needed laser treatments and re-treatments in the study eye at up to week 24	Number of additional needed laser treatments and re-treatments in the study eye at up to week 24	24 weeks	No
Secondary	Required intensity of laser spots of additional laser treatments and re-treatments in the study eye at up to week 24	Required intensity of laser spots of additional laser treatments and re-treatments in the study eye at up to week 24	24 weeks	No
Secondary	Retinal non-perfusion area	The change from baseline in size of retinal non-perfusion areas in the study eye to week 24	24 weeks	No
Secondary	Retinal Thickness	Absolute change from baseline in retinal thickness in the study eye, assessed by spectral domain optical coherence tomography (SD-OCT) at week 24	24 weeks	No
Secondary	Quality of Life	The change from baseline in the NEI-VFQ-25 health questionnaire total score to week 24	24 weeks	No
Secondary	Quality of Life on EQ-5D	The change from baseline in the EQ-5D health questionnaire score to week 24	24 weeks	No
Secondary	Safety: Incidence of treatment-emergent Adverse Events	Incidence, causality and intensity of adverse events between the treatment arms	24 weeks	Yes