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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
Gene Signal SAS
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ischaemic Central Retinal Vein Occlusion

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

    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
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    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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