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The IAI-OCTA Study; a Study of OCT-Angiography Analysis Efficacy (IAI-OCTA)

Primary Purpose

Wet Macular Degeneration

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Aflibercept Ophthalmic
optovue angiovue
Sponsored by
University of California, Los Angeles
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Wet Macular Degeneration

Eligibility Criteria

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

Inclusion Criteria:

  1. Subject is older than 50 years of age.
  2. Subject is willing to participate in the study and able to follow the study criteria and protocol.
  3. The study eye is treatment naive regarding treatment of neovascular AMD.
  4. Subject is willing and able to comply with clinic visits and study-related procedures.
  5. Subject is able to provide signed informed consent.
  6. Subject is able to understand and complete study-related questionnaires.
  7. The subject is not currently involved with any other clinical study.
  8. Best Corrected Visual Acuity (BCVA) with ETDRS Snellen equivalent of 20/400 or better and 20/32 or worse.
  9. Sufficiently clear media (cornea, anterior chamber, lens, vitreous) for OCT, FA and fundus photography (FP).
  10. Intraocular pressure (IOP) of 25mmHg or less in the study eye, with or without use of ocular hypotensive agents.
  11. Prior focal corticosteroid treatment is allowed, as long as the study eye is not involved. However prior (within 90 days of Day 0) or current systemic corticosteroid therapy (oral or intravenous corticosteroid treatment) is not permitted.

Exclusion Criteria:

  1. Any prior treatment of neovascular AMD in the eye proposed for enrollment including previous anti-vascular endothelial factor (anti-VEGF) therapy, photodynamic therapy (PDT), radiation therapy, corticosteroid treatment, surgical treatment for CNV, thermal laser treatment, and any other prior intravitreal treatment for neovascular AMD (except minerals and vitamins).
  2. Known serious allergies to aflibercept, fluorescein dye, Indocyanine Green (ICG), shellfish, drugs for pupillary dilation, topical anesthetic, or sterilizing solution (e.g. Betadine Solution).
  3. Prior or current systemic anti-VEGF therapy.
  4. Pregnant or breast-feeding women.
  5. Sexually active men* or women of childbearing potential** who are unwilling to practice adequate contraception during the study (adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device [IUD]; bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly).
  6. Contraindication to pupillary dilation in study eye.
  7. Any condition (including inability to read visual acuity charts, or language barrier) that may preclude subjects ability to comply with the study protocol and requirements.
  8. Presence of any advanced systemic condition or end-stage disease, such as advanced Alzheimer Syndrome, end-stage cancer, etc., which will likely prevent subject from completing study.
  9. Previous therapeutic radiation in the region of the study eye.
  10. Prior retinal pigment epithelial (RPE) tear in study eye.
  11. Prior ocular surgery (except YAG laser capsulotomy) for study within the past 90 days.
  12. Anticipated ocular surgery (except YAG laser capsulotomy) for the next 12 months.
  13. Prior vitrectomy in the study eye.
  14. Presence of any causes of CNV and PED other than due to AMD or presence of ocular disease other than AMD affecting study eye, i.e. presumed ocular histoplasmosis syndrome, android streaks, pathologic myopia

Sites / Locations

  • Stein Eye Institute of UCLA

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

IAI Treatment

Arm Description

Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Additional injections can be administered during the remaining visits on an as needed basis per Primary Investigator (PI) discretion based on the presence of any intraretinal or subretinal fluid on OCT, heme visualized on examination, reduction of BCVA by 5 or more ETDRS letters, or evidence of either increased area, density, or activity of the brush border of the neovascularization on OCT-angiography. There will be a minimum of 21 days between subsequent injections. Each subject will therefore receive a minimum of 7 injections and up to a maximum of 13 injections throughout the study period.

Outcomes

Primary Outcome Measures

Area of Lesion Measured by Optical Coherence Tomography Angiography (OCTA) Scan.
Area of the neovascular lesion (in millimeters^2)
Area of Lesion Measured by Optical Coherence Tomography Angiography (OCTA) Scan.
Area of the neovascular lesion (in millimeters^2)

Secondary Outcome Measures

Best Corrected Visual Acuity (BCVA) -Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Change
patients with gain of ≥5, ≥10, or ≥15 ETDRS letters. The ETDRS chart is read at 4.0 meters, and presents a series of five letters of equal difficulty on each row, with standardized spacing between letters and rows, for a total of 14 lines (70 letters).
Best Corrected Visual Acuity (BCVA) -ETDRS Letter Change
patients with gain of ≥5, ≥10, or ≥15 ETDRS letters. The ETDRS chart is read at 4.0 meters, and presents a series of five letters of equal difficulty on each row, with standardized spacing between letters and rows, for a total of 14 lines (70 letters).
Mean Best Corrected Visual Acuity (BCVA)
Visual acuity (VA) was assessed at a distance of 4 meters from Snellen and converted to logarithm minimum angle of resolution (logMAR). A logMAR value of 0 equates to 20/20 Snellen visual acuity (normal distance eyesight), with a lower logMAR value indicating better visual acuity.
Mean Best Corrected Visual Acuity (BCVA)
Visual acuity (VA) was assessed at a distance of 4 meters from Snellen and converted to logarithm minimum angle of resolution (logMAR). A logMAR value of 0 equates to 20/20 Snellen visual acuity (normal distance eyesight), with a lower logMAR value indicating better visual acuity.

Full Information

First Posted
November 10, 2016
Last Updated
December 9, 2021
Sponsor
University of California, Los Angeles
Collaborators
Regeneron Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT03022292
Brief Title
The IAI-OCTA Study; a Study of OCT-Angiography Analysis Efficacy
Acronym
IAI-OCTA
Official Title
The IAI-OCTA Study or; Microvascular Structure and Morphology of Neovascular Membranes in Age Related Macular Degeneration (AMD) After Intravitreal Aflibercept Injection (IAI) Therapy Using OCT-Angiography Analysis
Study Type
Interventional

2. Study Status

Record Verification Date
December 2021
Overall Recruitment Status
Completed
Study Start Date
March 30, 2017 (Actual)
Primary Completion Date
June 25, 2020 (Actual)
Study Completion Date
August 31, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, Los Angeles
Collaborators
Regeneron Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
A study investigating the ability of OCTA imaging technology to identify and analyze untreated type 1, 2, and 3 neovascular membrane lesions in treatment naive patients with exudative macular degeneration, as well as investigating the ability of the OCTA imaging technology to evaluate the treatment outcomes of Intravitreal Aflibercept Injection in neovascular lesions associated with macular degeneration. This study is utilizing a new, FDA approved, non-standard of care technology (OCT-Angiography by Optovue) to image and evaluate the treatment outcomes of using standard of care Intravitreal Aflibercept Injections for their approved use in patients diagnosed with neovascular AMD who are naive to previous Anti-VEGF therapies.
Detailed Description
Prospective study of neovascular AMD subjects with type 1, 2, or 3 neovascularization that have not been treated with prior anti-VEGF therapy. Subjects will be scheduled for intravitreal aflibercept injection (IAI) at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Additional injections can be administered during the remaining visits on an as needed basis per PI discretion based on the presence of any intraretinal or subretinal fluid on OCT, heme visualized on examination, reduction of BCVA by 5 or more ETDRS letters, or evidence of either increased area, density, or activity of the brush border of the neovascularization on OCT angiography. There will be a minimum of 21 days between subsequent injections. Each subject will therefore receive a minimum of 7 injections and up to a maximum of 13 injections throughout the study period. No injection will be given on the exit visit, week 52. OCT angiography and spectral domain OCT imaging will be performed at baseline and every 4 weeks thereafter The above procedures are standard of care for neovascular AMD subjects. As part of this study, these subjects will also undergo imaging of both eyes with OCTA at each visit. This is not standard of Care and is research. The only procedure that is being performed for research is the OCT-A. The injections and all other procedure are SOC based on physician discretion and clinical need. The investigators will not be modifying the dosage amounts or frequency. A subgroup of willing subjects will undergo OCT angiography every 2 weeks for the first 12 weeks. Indocyanine green angiography will be performed at baseline for all subjects to establish baseline subject population characteristics. Fluorescein angiography will be performed at baseline, week 12, and week 52 for efficacy monitoring. Detailed OCT angiography analysis will be performed to identify anatomical and morphological biomarkers of growth progression and disease activity. In addition to qualitative structural and morphological analysis, detailed quantitative OCT angiography analysis of the neovascular lesion using automated or manual capillary density maps and area calculation will be performed at each visit to determine the detailed microvascular response of neovascular complexes to IAI therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Wet Macular Degeneration

7. Study Design

Primary Purpose
Other
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
26 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IAI Treatment
Arm Type
Experimental
Arm Description
Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Additional injections can be administered during the remaining visits on an as needed basis per Primary Investigator (PI) discretion based on the presence of any intraretinal or subretinal fluid on OCT, heme visualized on examination, reduction of BCVA by 5 or more ETDRS letters, or evidence of either increased area, density, or activity of the brush border of the neovascularization on OCT-angiography. There will be a minimum of 21 days between subsequent injections. Each subject will therefore receive a minimum of 7 injections and up to a maximum of 13 injections throughout the study period.
Intervention Type
Drug
Intervention Name(s)
Aflibercept Ophthalmic
Intervention Description
IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC
Intervention Type
Device
Intervention Name(s)
optovue angiovue
Other Intervention Name(s)
OCTA
Intervention Description
FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.
Primary Outcome Measure Information:
Title
Area of Lesion Measured by Optical Coherence Tomography Angiography (OCTA) Scan.
Description
Area of the neovascular lesion (in millimeters^2)
Time Frame
Week 24
Title
Area of Lesion Measured by Optical Coherence Tomography Angiography (OCTA) Scan.
Description
Area of the neovascular lesion (in millimeters^2)
Time Frame
Week 52
Secondary Outcome Measure Information:
Title
Best Corrected Visual Acuity (BCVA) -Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Change
Description
patients with gain of ≥5, ≥10, or ≥15 ETDRS letters. The ETDRS chart is read at 4.0 meters, and presents a series of five letters of equal difficulty on each row, with standardized spacing between letters and rows, for a total of 14 lines (70 letters).
Time Frame
Baseline, Week 24
Title
Best Corrected Visual Acuity (BCVA) -ETDRS Letter Change
Description
patients with gain of ≥5, ≥10, or ≥15 ETDRS letters. The ETDRS chart is read at 4.0 meters, and presents a series of five letters of equal difficulty on each row, with standardized spacing between letters and rows, for a total of 14 lines (70 letters).
Time Frame
Week 24, Week 52
Title
Mean Best Corrected Visual Acuity (BCVA)
Description
Visual acuity (VA) was assessed at a distance of 4 meters from Snellen and converted to logarithm minimum angle of resolution (logMAR). A logMAR value of 0 equates to 20/20 Snellen visual acuity (normal distance eyesight), with a lower logMAR value indicating better visual acuity.
Time Frame
Week 24
Title
Mean Best Corrected Visual Acuity (BCVA)
Description
Visual acuity (VA) was assessed at a distance of 4 meters from Snellen and converted to logarithm minimum angle of resolution (logMAR). A logMAR value of 0 equates to 20/20 Snellen visual acuity (normal distance eyesight), with a lower logMAR value indicating better visual acuity.
Time Frame
Week 52
Other Pre-specified Outcome Measures:
Title
OCTA Neovascular Membrane Regression Ratio of Change
Description
OCT angiography regression of neovascular membrane as measured by ratio of change in area of the neovascular lesion (in millimeters^2) during the initial 12 weeks
Time Frame
12 weeks
Title
Presence of Intraretinal and Subretinal Fluid, and Subretinal Hyper-Reflective Material (SHRM) on Spectral Domain Optical Coherence Tomography (SD-OCT) Scan.
Description
Participants with presence of intraretinal and subretinal fluid, and Subretinal Hyper-Reflective Material (SHRM)
Time Frame
week 24
Title
SD OCT Presence of Intraretinal and Subretinal Fluid, and Subretinal Hyper-Reflective Material (SHRM)
Description
Participants with presence of SD OCT intraretinal and subretinal fluid, and Subretinal Hyper-Reflective Material (SHRM)
Time Frame
week 52
Title
Ocular AE
Description
ocular adverse events
Time Frame
52 weeks
Title
Relevant Systemic SAE
Description
relevant systemic serious adverse events
Time Frame
52 weeks
Title
Number of Injections
Time Frame
week 24
Title
Number of Injections
Time Frame
week 52
Title
OCTA Neovascular Membrane Biomarker Qualitative Analysis (Sub-study)
Description
In subjects participating in the sub-study of serial OCT Angiography during the initial 12 weeks OCT angiography qualitative analysis of morphological biomarkers of the neovascular complex including attenuation of the fringe during the initial 12 weeks
Time Frame
Week 1-12
Title
SD OCT Analysis of Central Macular Thickness
Description
Ratio of change in SD OCT central macular thickness, calculated as change between visits divided by baseline measure.
Time Frame
Baseline to week 24
Title
SD OCT Analysis of Central Macular Thickness
Description
Ratio of change in SD OCT central macular thickness, calculated as change between visits divided by baseline measure.
Time Frame
Baseline to week 52
Title
OCTA Analysis of Vessel Density
Description
OCT angiography ratio of change in neovascular membrane as measured by area of the neovascular lesion in mm^2 at baseline and week 24. Ratio of change was calculated as change from baseline divided by the baseline value.
Time Frame
24 weeks
Title
OCTA Neovascular Membrane Biomarker Qualitative Analysis of Flow-void Areas(Sub-study)
Description
In subjects participating in the sub-study of serial OCT Angiography during the initial 12 weeks) OCT angiography qualitative analysis of morphological biomarkers of the neovascular complex including presence of flow-void areas during the initial 12 weeks
Time Frame
Week 1-12
Title
OCTA Neovascular Membrane Biomarker Qualitative Analysis of Vessel Looping (Sub-study)
Description
In subjects participating in the sub-study of serial OCT Angiography during the initial 12 weeks) OCT angiography qualitative analysis of morphological biomarkers of the neovascular complex including changes in vessel looping during the initial 12 weeks
Time Frame
Week 1-12
Title
SD OCT Analysis of SRF Volume
Description
Change in volume of subretinal fluid
Time Frame
week 24 and 52
Title
SD OCT Analysis of SHRM Volume
Description
Change volume of SHRM
Time Frame
week 24 and 52
Title
Presence of CME (Cystoid Macular Edema) on Spectral Domain Optical Coherence Tomography (SD-OCT) Scan.
Description
Participants with presence of cystoid macular edema
Time Frame
week 24
Title
Presence of CME (Cystoid Macular Edema) on Spectral Domain Optical Coherence Tomography (SD-OCT) Scan.
Description
Participants with presence of cystoid macular edema
Time Frame
week 52
Title
Pigment Epithelial Detachment (PED) Volume as Determined by SD OCT Analysis
Description
Change in ratio of volume of pigment epithelial detachment (PED), calculated as change from baseline divided by baseline value.
Time Frame
Baseline to week 24
Title
PED Volume as Determined by SD OCT Analysis
Description
Change in ratio of volume of PED, calculated as change from baseline divided by baseline value.
Time Frame
Baseline to Week 52
Title
PED Height as Determined by SD OCT Analysis
Description
Ratio of change in height of PED, calculated as change from baseline divided by baseline value
Time Frame
Baseline, week 24
Title
PED Height as Determined by SD OCT Analysis
Description
Ratio of change in height of PED, calculated as change from baseline divided by baseline value
Time Frame
Baseline, week 52

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subject is older than 50 years of age. Subject is willing to participate in the study and able to follow the study criteria and protocol. The study eye is treatment naive regarding treatment of neovascular AMD. Subject is willing and able to comply with clinic visits and study-related procedures. Subject is able to provide signed informed consent. Subject is able to understand and complete study-related questionnaires. The subject is not currently involved with any other clinical study. Best Corrected Visual Acuity (BCVA) with ETDRS Snellen equivalent of 20/400 or better and 20/32 or worse. Sufficiently clear media (cornea, anterior chamber, lens, vitreous) for OCT, FA and fundus photography (FP). Intraocular pressure (IOP) of 25mmHg or less in the study eye, with or without use of ocular hypotensive agents. Prior focal corticosteroid treatment is allowed, as long as the study eye is not involved. However prior (within 90 days of Day 0) or current systemic corticosteroid therapy (oral or intravenous corticosteroid treatment) is not permitted. Exclusion Criteria: Any prior treatment of neovascular AMD in the eye proposed for enrollment including previous anti-vascular endothelial factor (anti-VEGF) therapy, photodynamic therapy (PDT), radiation therapy, corticosteroid treatment, surgical treatment for CNV, thermal laser treatment, and any other prior intravitreal treatment for neovascular AMD (except minerals and vitamins). Known serious allergies to aflibercept, fluorescein dye, Indocyanine Green (ICG), shellfish, drugs for pupillary dilation, topical anesthetic, or sterilizing solution (e.g. Betadine Solution). Prior or current systemic anti-VEGF therapy. Pregnant or breast-feeding women. Sexually active men* or women of childbearing potential** who are unwilling to practice adequate contraception during the study (adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device [IUD]; bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly). Contraindication to pupillary dilation in study eye. Any condition (including inability to read visual acuity charts, or language barrier) that may preclude subjects ability to comply with the study protocol and requirements. Presence of any advanced systemic condition or end-stage disease, such as advanced Alzheimer Syndrome, end-stage cancer, etc., which will likely prevent subject from completing study. Previous therapeutic radiation in the region of the study eye. Prior retinal pigment epithelial (RPE) tear in study eye. Prior ocular surgery (except YAG laser capsulotomy) for study within the past 90 days. Anticipated ocular surgery (except YAG laser capsulotomy) for the next 12 months. Prior vitrectomy in the study eye. Presence of any causes of CNV and PED other than due to AMD or presence of ocular disease other than AMD affecting study eye, i.e. presumed ocular histoplasmosis syndrome, android streaks, pathologic myopia
Facility Information:
Facility Name
Stein Eye Institute of UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
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The IAI-OCTA Study; a Study of OCT-Angiography Analysis Efficacy

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