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

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

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.

Study Overview

• Status: Completed
• Conditions: Wet Macular Degeneration
• Intervention / Treatment: Drug: Aflibercept Ophthalmic; Device: optovue angiovue

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.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Stein Eye Institute of UCLA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: IAI Treatment; 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.

Drug: Aflibercept Ophthalmic; IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC; Device: optovue angiovue; FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.; Other Names: OCTA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area of Lesion Measured by Optical Coherence Tomography Angiography (OCTA) Scan.	Area of the neovascular lesion (in millimeters^2)	Week 24
Area of Lesion Measured by Optical Coherence Tomography Angiography (OCTA) Scan.	Area of the neovascular lesion (in millimeters^2)	Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Baseline, Week 24
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).	Week 24, Week 52
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.	Week 24
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.	Week 52

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
OCTA Neovascular Membrane Regression Ratio of Change	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	12 weeks
Presence of Intraretinal and Subretinal Fluid, and Subretinal Hyper-Reflective Material (SHRM) on Spectral Domain Optical Coherence Tomography (SD-OCT) Scan.	Participants with presence of intraretinal and subretinal fluid, and Subretinal Hyper-Reflective Material (SHRM)	week 24
SD OCT Presence of Intraretinal and Subretinal Fluid, and Subretinal Hyper-Reflective Material (SHRM)	Participants with presence of SD OCT intraretinal and subretinal fluid, and Subretinal Hyper-Reflective Material (SHRM)	week 52
Ocular AE	ocular adverse events	52 weeks
Relevant Systemic SAE	relevant systemic serious adverse events	52 weeks
Number of Injections		week 24
Number of Injections		week 52
OCTA Neovascular Membrane Biomarker Qualitative Analysis (Sub-study)	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	Week 1-12
SD OCT Analysis of Central Macular Thickness	Ratio of change in SD OCT central macular thickness, calculated as change between visits divided by baseline measure.	Baseline to week 24
SD OCT Analysis of Central Macular Thickness	Ratio of change in SD OCT central macular thickness, calculated as change between visits divided by baseline measure.	Baseline to week 52
OCTA Analysis of Vessel Density	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.	24 weeks
OCTA Neovascular Membrane Biomarker Qualitative Analysis of Flow-void Areas(Sub-study)	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	Week 1-12
OCTA Neovascular Membrane Biomarker Qualitative Analysis of Vessel Looping (Sub-study)	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	Week 1-12
SD OCT Analysis of SRF Volume	Change in volume of subretinal fluid	week 24 and 52
SD OCT Analysis of SHRM Volume	Change volume of SHRM	week 24 and 52
Presence of CME (Cystoid Macular Edema) on Spectral Domain Optical Coherence Tomography (SD-OCT) Scan.	Participants with presence of cystoid macular edema	week 24
Presence of CME (Cystoid Macular Edema) on Spectral Domain Optical Coherence Tomography (SD-OCT) Scan.	Participants with presence of cystoid macular edema	week 52
Pigment Epithelial Detachment (PED) Volume as Determined by SD OCT Analysis	Change in ratio of volume of pigment epithelial detachment (PED), calculated as change from baseline divided by baseline value.	Baseline to week 24
PED Volume as Determined by SD OCT Analysis	Change in ratio of volume of PED, calculated as change from baseline divided by baseline value.	Baseline to Week 52
PED Height as Determined by SD OCT Analysis	Ratio of change in height of PED, calculated as change from baseline divided by baseline value	Baseline, week 24
PED Height as Determined by SD OCT Analysis	Ratio of change in height of PED, calculated as change from baseline divided by baseline value	Baseline, week 52

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: Regeneron Pharmaceuticals

Publications and helpful links

General Publications

• Congdon N, O'Colmain B, Klaver CC, Klein R, Munoz B, Friedman DS, Kempen J, Taylor HR, Mitchell P; Eye Diseases Prevalence Research Group. Causes and prevalence of visual impairment among adults in the United States. Arch Ophthalmol. 2004 Apr;122(4):477-85. doi: 10.1001/archopht.122.4.477.
• Solomon SD, Lindsley K, Vedula SS, Krzystolik MG, Hawkins BS. Anti-vascular endothelial growth factor for neovascular age-related macular degeneration. Cochrane Database Syst Rev. 2014 Aug 29;8(8):CD005139. doi: 10.1002/14651858.CD005139.pub3.
• Kuehlewein L, Bansal M, Lenis TL, Iafe NA, Sadda SR, Bonini Filho MA, De Carlo TE, Waheed NK, Duker JS, Sarraf D. Optical Coherence Tomography Angiography of Type 1 Neovascularization in Age-Related Macular Degeneration. Am J Ophthalmol. 2015 Oct;160(4):739-48.e2. doi: 10.1016/j.ajo.2015.06.030. Epub 2015 Jul 9.
• Kuehlewein L, Dansingani KK, de Carlo TE, Bonini Filho MA, Iafe NA, Lenis TL, Freund KB, Waheed NK, Duker JS, Sadda SR, Sarraf D. OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF TYPE 3 NEOVASCULARIZATION SECONDARY TO AGE-RELATED MACULAR DEGENERATION. Retina. 2015 Nov;35(11):2229-35. doi: 10.1097/IAE.0000000000000835.
• Miere A, Querques G, Semoun O, El Ameen A, Capuano V, Souied EH. OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN EARLY TYPE 3 NEOVASCULARIZATION. Retina. 2015 Nov;35(11):2236-41. doi: 10.1097/IAE.0000000000000834.
• El Ameen A, Cohen SY, Semoun O, Miere A, Srour M, Quaranta-El Maftouhi M, Oubraham H, Blanco-Garavito R, Querques G, Souied EH. TYPE 2 NEOVASCULARIZATION SECONDARY TO AGE-RELATED MACULAR DEGENERATION IMAGED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY. Retina. 2015 Nov;35(11):2212-8. doi: 10.1097/IAE.0000000000000773.
• Jia Y, Bailey ST, Wilson DJ, Tan O, Klein ML, Flaxel CJ, Potsaid B, Liu JJ, Lu CD, Kraus MF, Fujimoto JG, Huang D. Quantitative optical coherence tomography angiography of choroidal neovascularization in age-related macular degeneration. Ophthalmology. 2014 Jul;121(7):1435-44. doi: 10.1016/j.ophtha.2014.01.034. Epub 2014 Mar 27.
• Miere A, Semoun O, Cohen SY, El Ameen A, Srour M, Jung C, Oubraham H, Querques G, Souied EH. OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FEATURES OF SUBRETINAL FIBROSIS IN AGE-RELATED MACULAR DEGENERATION. Retina. 2015 Nov;35(11):2275-84. doi: 10.1097/IAE.0000000000000819.
• Coscas G, Lupidi M, Coscas F, Francais C, Cagini C, Souied EH. Optical coherence tomography angiography during follow-up: qualitative and quantitative analysis of mixed type I and II choroidal neovascularization after vascular endothelial growth factor trap therapy. Ophthalmic Res. 2015;54(2):57-63. doi: 10.1159/000433547. Epub 2015 Jul 17.
• Spaide RF. Optical Coherence Tomography Angiography Signs of Vascular Abnormalization With Antiangiogenic Therapy for Choroidal Neovascularization. Am J Ophthalmol. 2015 Jul;160(1):6-16. doi: 10.1016/j.ajo.2015.04.012. Epub 2015 Apr 14.
• Schmidt-Erfurth U, Kaiser PK, Korobelnik JF, Brown DM, Chong V, Nguyen QD, Ho AC, Ogura Y, Simader C, Jaffe GJ, Slakter JS, Yancopoulos GD, Stahl N, Vitti R, Berliner AJ, Soo Y, Anderesi M, Sowade O, Zeitz O, Norenberg C, Sandbrink R, Heier JS. Intravitreal aflibercept injection for neovascular age-related macular degeneration: ninety-six-week results of the VIEW studies. Ophthalmology. 2014 Jan;121(1):193-201. doi: 10.1016/j.ophtha.2013.08.011. Epub 2013 Sep 29.

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2017
• Primary Completion (Actual): June 25, 2020
• Study Completion (Actual): August 31, 2020

Study Registration Dates

• First Submitted: November 10, 2016
• First Submitted That Met QC Criteria: January 11, 2017
• First Posted (Estimate): January 16, 2017

Study Record Updates

• Last Update Posted (Actual): January 6, 2022
• Last Update Submitted That Met QC Criteria: December 9, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Wet Macular Degeneration; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept
• Other Study ID Numbers: 16-000925

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• 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