Clinical trial NCT03022292: The IAI-OCTA Study; a Study of OCT-Angiography Analysis Efficacy
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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Wet Macular Degeneration
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2017-01-16
Enrollment: 26
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: Area of Lesion Measured by Optical Coherence Tomography Angiography (OCTA) Scan.
timeFrame: Week 24
measure: Area of Lesion Measured by Optical Coherence Tomography Angiography (OCTA) Scan.
timeFrame: Week 52
Secondary outcomes:
measure: Best Corrected Visual Acuity (BCVA) -Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Change
timeFrame: Baseline, Week 24
measure: Best Corrected Visual Acuity (BCVA) -ETDRS Letter Change
timeFrame: Week 24, Week 52
measure: Mean Best Corrected Visual Acuity (BCVA)
timeFrame: Week 24
measure: Mean Best Corrected Visual Acuity (BCVA)
timeFrame: Week 52
Other outcomes:
measure: OCTA Neovascular Membrane Regression Ratio of Change
timeFrame: 12 weeks
measure: Presence of Intraretinal and Subretinal Fluid, and Subretinal Hyper-Reflective Material (SHRM) on Spectral Domain Optical Coherence Tomography (SD-OCT) Scan.
timeFrame: week 24
measure: SD OCT Presence of Intraretinal and Subretinal Fluid, and Subretinal Hyper-Reflective Material (SHRM)
timeFrame: week 52
measure: Ocular AE
timeFrame: 52 weeks
measure: Relevant Systemic SAE
timeFrame: 52 weeks
measure: Number of Injections
timeFrame: week 24
measure: Number of Injections
timeFrame: week 52
measure: OCTA Neovascular Membrane Biomarker Qualitative Analysis (Sub-study)
timeFrame: Week 1-12
measure: SD OCT Analysis of Central Macular Thickness
timeFrame: Baseline to week 24
measure: SD OCT Analysis of Central Macular Thickness
timeFrame: Baseline to week 52
measure: OCTA Analysis of Vessel Density
timeFrame: 24 weeks
measure: OCTA Neovascular Membrane Biomarker Qualitative Analysis of Flow-void Areas(Sub-study)
timeFrame: Week 1-12
measure: OCTA Neovascular Membrane Biomarker Qualitative Analysis of Vessel Looping (Sub-study)
timeFrame: Week 1-12
measure: SD OCT Analysis of SRF Volume
timeFrame: week 24 and 52
measure: SD OCT Analysis of SHRM Volume
timeFrame: week 24 and 52
measure: Presence of CME (Cystoid Macular Edema) on Spectral Domain Optical Coherence Tomography (SD-OCT) Scan.
timeFrame: week 24
measure: Presence of CME (Cystoid Macular Edema) on Spectral Domain Optical Coherence Tomography (SD-OCT) Scan.
timeFrame: week 52
measure: Pigment Epithelial Detachment (PED) Volume as Determined by SD OCT Analysis
timeFrame: Baseline to week 24
measure: PED Volume as Determined by SD OCT Analysis
timeFrame: Baseline to Week 52
measure: PED Height as Determined by SD OCT Analysis
timeFrame: Baseline, week 24
measure: PED Height as Determined by SD OCT Analysis
timeFrame: Baseline, week 52
Locations:
city: Los Angeles
country: United States
facility: Stein Eye Institute of UCLA
state: California
Study officials:
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