Trial of Aganirsen in iCRVO Patients at Risk of Developing NVG (STRONG)
Primary Purpose
Ischaemic Central Retinal Vein Occlusion, Neovascular Glaucoma
Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
aganirsen
Sponsored by
About this trial
This is an interventional treatment trial 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
aganirsen "low-dose":
aganirsen "high-dose"
aganirsen placebo (vehicle)
Arm Description
43µg daily, one drop of 0.86 mg/g emulsion (morning) + one drop of placebo (evening) daily
86µg daily, one drop of 0.86 mg/g emulsion twice daily (morning and evening)
one drop of placebo emulsion (morning) + one drop of placebo emulsion (evening) daily
Outcomes
Primary Outcome Measures
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
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
Secondary Outcome Measures
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).
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.
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
Visual Acuity
The change from baseline in BCVA (EDTRS letter score) in the study eye to week 24.
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
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
Retinal non-perfusion area
The change from baseline in size of retinal non-perfusion areas in the study eye to week 24
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
Quality of Life
The change from baseline in the NEI-VFQ-25 health questionnaire total score to week 24
Quality of Life on EQ-5D
The change from baseline in the EQ-5D health questionnaire score to week 24
Safety: Incidence of treatment-emergent Adverse Events
Incidence, causality and intensity of adverse events between the treatment arms
Full Information
NCT ID
NCT02947867
First Posted
October 15, 2016
Last Updated
October 28, 2016
Sponsor
Gene Signal SAS
Collaborators
Johannes Gutenberg University Mainz, University Hospital of Cologne, Moorfields Eye Hospital NHS Foundation Trust
1. Study Identification
Unique Protocol Identification Number
NCT02947867
Brief Title
Trial of Aganirsen in iCRVO Patients at Risk of Developing NVG
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2016
Overall Recruitment Status
Unknown status
Study Start Date
January 2017 (undefined)
Primary Completion Date
June 2019 (Anticipated)
Study Completion Date
December 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gene Signal SAS
Collaborators
Johannes Gutenberg University Mainz, University Hospital of Cologne, Moorfields Eye Hospital NHS Foundation Trust
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ischaemic Central Retinal Vein Occlusion, Neovascular Glaucoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
333 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
aganirsen "low-dose":
Arm Type
Experimental
Arm Description
43µg daily, one drop of 0.86 mg/g emulsion (morning) + one drop of placebo (evening) daily
Arm Title
aganirsen "high-dose"
Arm Type
Experimental
Arm Description
86µg daily, one drop of 0.86 mg/g emulsion twice daily (morning and evening)
Arm Title
aganirsen placebo (vehicle)
Arm Type
Placebo Comparator
Arm Description
one drop of placebo emulsion (morning) + one drop of placebo emulsion (evening) daily
Intervention Type
Drug
Intervention Name(s)
aganirsen
Other Intervention Name(s)
GS-101
Intervention Description
aganirsen antisense oligonucleotide against Insulin Receptor Substrate (IRS-1)
Primary Outcome Measure Information:
Title
NVG component
Description
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
Time Frame
Week 24
Title
IOP component
Description
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
Time Frame
Week 24
Secondary Outcome Measure Information:
Title
Secondary NVG
Description
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).
Time Frame
24 weeks
Title
Anterior segment neovascularisation
Description
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.
Time Frame
24 weeks
Title
NVG Classification
Description
NVG Classification at 24 weeks on a scale from 1 (non-NVG) to 6 (most advanced NVG) based on central reading of neovascularisation
Time Frame
24 weeks
Title
Visual Acuity
Description
The change from baseline in BCVA (EDTRS letter score) in the study eye to week 24.
Time Frame
24 weeks
Title
Number of additional needed laser treatments and re-treatments in the study eye at up to week 24
Description
Number of additional needed laser treatments and re-treatments in the study eye at up to week 24
Time Frame
24 weeks
Title
Required intensity of laser spots of additional laser treatments and re-treatments in the study eye at up to week 24
Description
Required intensity of laser spots of additional laser treatments and re-treatments in the study eye at up to week 24
Time Frame
24 weeks
Title
Retinal non-perfusion area
Description
The change from baseline in size of retinal non-perfusion areas in the study eye to week 24
Time Frame
24 weeks
Title
Retinal Thickness
Description
Absolute change from baseline in retinal thickness in the study eye, assessed by spectral domain optical coherence tomography (SD-OCT) at week 24
Time Frame
24 weeks
Title
Quality of Life
Description
The change from baseline in the NEI-VFQ-25 health questionnaire total score to week 24
Time Frame
24 weeks
Title
Quality of Life on EQ-5D
Description
The change from baseline in the EQ-5D health questionnaire score to week 24
Time Frame
24 weeks
Title
Safety: Incidence of treatment-emergent Adverse Events
Description
Incidence, causality and intensity of adverse events between the treatment arms
Time Frame
24 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Katrin Lorenz, MD
Phone
+49613117
Ext
4069
Email
katrin.lorenz@unimedizin-mainz.de
First Name & Middle Initial & Last Name or Official Title & Degree
Yvonne Scheller, PhD
Phone
+49613117
Ext
3367
Email
yvonne.scheller@unimedizin-mainz.de
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
28302155
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.
Results Reference
derived
Learn more about this trial
Trial of Aganirsen in iCRVO Patients at Risk of Developing NVG
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