Trial of Aganirsen in iCRVO Patients at Risk of Developing NVG (STRONG)

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

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

Study Overview

• Status: Unknown
• Conditions: Neovascular Glaucoma; Ischaemic Central Retinal Vein Occlusion
• Intervention / Treatment: Drug: aganirsen

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.

• Study Type: Interventional
• Enrollment (Anticipated): 333
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Katrin Lorenz, MD; Phone Number: 4069 +49613117; Email: katrin.lorenz@unimedizin-mainz.de
• Study Contact Backup: Name: Yvonne Scheller, PhD; Phone Number: 3367 +49613117; Email: yvonne.scheller@unimedizin-mainz.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: aganirsen "low-dose": 43µg daily, one drop of 0.86 mg/g emulsion (morning) + one drop of placebo (evening) daily	Drug: aganirsen; aganirsen antisense oligonucleotide against Insulin Receptor Substrate (IRS-1); Other Names: GS-101
EXPERIMENTAL: aganirsen "high-dose"; 86µg daily, one drop of 0.86 mg/g emulsion twice daily (morning and evening)	Drug: aganirsen; aganirsen antisense oligonucleotide against Insulin Receptor Substrate (IRS-1); Other Names: GS-101
PLACEBO_COMPARATOR: aganirsen placebo (vehicle); one drop of placebo emulsion (morning) + one drop of placebo emulsion (evening) daily	Drug: aganirsen; aganirsen antisense oligonucleotide against Insulin Receptor Substrate (IRS-1); Other Names: GS-101

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
Visual Acuity	The change from baseline in BCVA (EDTRS letter score) in the study eye to week 24.	24 weeks
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
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
Retinal non-perfusion area	The change from baseline in size of retinal non-perfusion areas in the study eye to week 24	24 weeks
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
Quality of Life	The change from baseline in the NEI-VFQ-25 health questionnaire total score to week 24	24 weeks
Quality of Life on EQ-5D	The change from baseline in the EQ-5D health questionnaire score to week 24	24 weeks
Safety: Incidence of treatment-emergent Adverse Events	Incidence, causality and intensity of adverse events between the treatment arms	24 weeks

Collaborators and Investigators

• Sponsor: Gene Signal SAS
• Collaborators: Moorfields Eye Hospital NHS Foundation Trust; Johannes Gutenberg University Mainz; University Hospital of Cologne

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2017
• Primary Completion (ANTICIPATED): June 1, 2019
• Study Completion (ANTICIPATED): December 1, 2019

Study Registration Dates

• First Submitted: October 15, 2016
• First Submitted That Met QC Criteria: October 26, 2016
• First Posted (ESTIMATE): October 28, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): October 31, 2016
• Last Update Submitted That Met QC Criteria: October 28, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Ocular Hypertension; Retinal Diseases; Embolism and Thrombosis; Venous Thrombosis; Thrombosis; Glaucoma; Retinal Vein Occlusion; Glaucoma, Neovascular
• Other Study ID Numbers: GS-101-P1-NVR; 2014-000239-18 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO