EAGLE: Evaluating Genotypes Using Intravitreal Aflibercept Injection (EAGLE)
Primary Purpose
Macular Degeneration, Wet Macular Degeneration
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Intravitreal aflibercept injection
Sponsored by
About this trial
This is an interventional treatment trial for Macular Degeneration focused on measuring AMD, Wet AMD, Macular degeneration, Wet macular degeneration, Neovascularization, Retina, Retinal degeneration
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 50 years
- Naïve neovascular wet-AMD (has not received treatment before)
- Willing and able to comply with clinic visits and study-related procedures
- Provide signed informed consent
Exclusion Criteria:
- Previous therapy in study eye for AMD or other retinal disease which may be used in the treatment of AMD
- Previous subfoveal focal laser photocoagulation involving the foveal center in the study eye
- History of vitrectomy, submacular surgery, or other surgical intervention for AMD in the study eye
- Any concurrent intraocular condition in the study eye (e.g. diabetic retinopathy or glaucoma) that, in the opinion of the investigator, could either 4.1 require medical or surgical intervention during the study period to prevent or treat visual loss that might result from that condition, or 4.2 if allowed to progress untreated, could likely contribute to loss of at least 2 Snellen equivalent lines of best corrected visual acuity over the study period
- Active intraocular inflammation (grade trace or above) in the study eye, or history of idiopathic or autoimmune-associated uveitis in either eye
- Current vitreous hemorrhage in the study eye
- History of rhegmatogenous retinal detachment or macular hole (Stage 3 or 4) in the study eye
- Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye
- Aphakia, ACIOL, or unstable PCIOL
- Uncontrolled glaucoma in the study eye (defined as intraocular pressure ≥30 mmHg despite treatment with anti-glaucoma medication)
- 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)
- Any other condition that the investigator believes would pose a significant hazard to the patient if the investigational therapy were initiated *Contraception is not required for men with documented vasectomy. **Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of child bearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.
Sites / Locations
- Shiley Eye Center
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Treatment - On-Label
Arm Description
On-label intravitreal aflibercept (Eylea) injection 2 mg (0.05 mL) administered every 4 weeks for the first 3 months, followed by 2 mg (0.05 mL) intravitreal injection once every 8 weeks (2 months) with the option to treat monthly based on retreatment criteria for a total duration of 12 months
Outcomes
Primary Outcome Measures
Anatomic Response
The primary endpoint in the study is the correlation of CFH, HTRA1, VEGFA, C3, TIMP3, APOE, CETP, LIPC, TGFBR1, CFI, and CFB allele frequencies and VEGA expression in lymphoblastoid cell lines with response to intravitreal aflibercept injection treatment, based on anatomic outcomes:
Early response (at Month 3) - o On optical coherence tomography(SD-OCT)
Reduction in central retinal thickness by ≥ 50%, OR
Central retinal thickness <300 um, OR
Absence of retinal fluid
Later response (at Month 12) -
o On SD-OCT
Reduction in central retinal thickness by ≥ 50%, OR
Central retinal thickness < 300 um, OR
Absence of retinal fluid
Poor response, defined as no reduction of fluid or central retinal thickness at Month 12.
Secondary Outcome Measures
Visual/Treatment Response
The secondary endpoints are a correlation of CFH, VEGF, HTRA1, VEGFA, C3, TIMP3, APOE, CETP, LIPC, TGFBR1, CFI, and CFB allele frequencies:
With visual outcomes -
Early response, defined as a gain ≥ 0 letters at Month 3
Later response, defined as a gain ≥ 0 letters at Month 12
Poor response, defined as loss of visual acuity (gain <0 letters) at Month 12
With change in characteristics on fluorescein angiography and fundus photography (lesion size, lesion type, etc)
With number of injections through Month 12
o Mean number of intravitreal aflibercept injections required through Month 12 will be calculated for the group overall, and separately by response group (early, later, and no response to treatment).
Full Information
NCT ID
NCT02689518
First Posted
April 21, 2014
Last Updated
March 23, 2021
Sponsor
University of California, San Diego
Collaborators
Regeneron Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT02689518
Brief Title
EAGLE: Evaluating Genotypes Using Intravitreal Aflibercept Injection
Acronym
EAGLE
Official Title
Clinical and Genetic Assessment of Treatment Response in Patients With Age-related Macular Degeneration Using Intravitreal Aflibercept Injection
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
April 2014 (Actual)
Primary Completion Date
November 12, 2019 (Actual)
Study Completion Date
November 12, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, San Diego
Collaborators
Regeneron Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Clinical and genetic evaluation of individuals treated with intravitreal aflibercept injection (Eylea) for neovascular age-related macular degeneration (wet AMD)
Detailed Description
Clinical and genetic assessment of treatment response in patients with age-related macular degeneration using intravitreal aflibercept injection. This study seeks to determine if different genetic polymorphisms of vascular endothelial growth factor A (VEGF-A) and HtrA serine peptidase 1(HTRA1) and other genes correlate to the response to intravitreal aflibercept injection therapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Macular Degeneration, Wet Macular Degeneration
Keywords
AMD, Wet AMD, Macular degeneration, Wet macular degeneration, Neovascularization, Retina, Retinal degeneration
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment - On-Label
Arm Type
Other
Arm Description
On-label intravitreal aflibercept (Eylea) injection 2 mg (0.05 mL) administered every 4 weeks for the first 3 months, followed by 2 mg (0.05 mL) intravitreal injection once every 8 weeks (2 months) with the option to treat monthly based on retreatment criteria for a total duration of 12 months
Intervention Type
Drug
Intervention Name(s)
Intravitreal aflibercept injection
Other Intervention Name(s)
Eylea
Intervention Description
Intravitreal aflibercept injection 2 mg (0.05 mL) administered every 4 weeks for the first 3 months, followed by 2 mg (0.05 mL) intravitreal injection once every 8 weeks(2 months) with the option to treat monthly based on retreatment criteria for a total duration of 12 months.
Primary Outcome Measure Information:
Title
Anatomic Response
Description
The primary endpoint in the study is the correlation of CFH, HTRA1, VEGFA, C3, TIMP3, APOE, CETP, LIPC, TGFBR1, CFI, and CFB allele frequencies and VEGA expression in lymphoblastoid cell lines with response to intravitreal aflibercept injection treatment, based on anatomic outcomes:
Early response (at Month 3) - o On optical coherence tomography(SD-OCT)
Reduction in central retinal thickness by ≥ 50%, OR
Central retinal thickness <300 um, OR
Absence of retinal fluid
Later response (at Month 12) -
o On SD-OCT
Reduction in central retinal thickness by ≥ 50%, OR
Central retinal thickness < 300 um, OR
Absence of retinal fluid
Poor response, defined as no reduction of fluid or central retinal thickness at Month 12.
Time Frame
12 Months
Secondary Outcome Measure Information:
Title
Visual/Treatment Response
Description
The secondary endpoints are a correlation of CFH, VEGF, HTRA1, VEGFA, C3, TIMP3, APOE, CETP, LIPC, TGFBR1, CFI, and CFB allele frequencies:
With visual outcomes -
Early response, defined as a gain ≥ 0 letters at Month 3
Later response, defined as a gain ≥ 0 letters at Month 12
Poor response, defined as loss of visual acuity (gain <0 letters) at Month 12
With change in characteristics on fluorescein angiography and fundus photography (lesion size, lesion type, etc)
With number of injections through Month 12
o Mean number of intravitreal aflibercept injections required through Month 12 will be calculated for the group overall, and separately by response group (early, later, and no response to treatment).
Time Frame
12 Months
Other Pre-specified Outcome Measures:
Title
Safety - Incidence and Severity of Ocular and Non-ocular Adverse Events
Description
Incidence and severity of ocular and non-ocular adverse events using Aflibercept intravitreal injections will also be evaluated.
Time Frame
12 Months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥ 50 years
Naïve neovascular wet-AMD (has not received treatment before)
Willing and able to comply with clinic visits and study-related procedures
Provide signed informed consent
Exclusion Criteria:
Previous therapy in study eye for AMD or other retinal disease which may be used in the treatment of AMD
Previous subfoveal focal laser photocoagulation involving the foveal center in the study eye
History of vitrectomy, submacular surgery, or other surgical intervention for AMD in the study eye
Any concurrent intraocular condition in the study eye (e.g. diabetic retinopathy or glaucoma) that, in the opinion of the investigator, could either 4.1 require medical or surgical intervention during the study period to prevent or treat visual loss that might result from that condition, or 4.2 if allowed to progress untreated, could likely contribute to loss of at least 2 Snellen equivalent lines of best corrected visual acuity over the study period
Active intraocular inflammation (grade trace or above) in the study eye, or history of idiopathic or autoimmune-associated uveitis in either eye
Current vitreous hemorrhage in the study eye
History of rhegmatogenous retinal detachment or macular hole (Stage 3 or 4) in the study eye
Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye
Aphakia, ACIOL, or unstable PCIOL
Uncontrolled glaucoma in the study eye (defined as intraocular pressure ≥30 mmHg despite treatment with anti-glaucoma medication)
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)
Any other condition that the investigator believes would pose a significant hazard to the patient if the investigational therapy were initiated *Contraception is not required for men with documented vasectomy. **Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of child bearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Goldbaum, M.D.
Organizational Affiliation
UCSD
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shiley Eye Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92126
Country
United States
12. IPD Sharing Statement
Learn more about this trial
EAGLE: Evaluating Genotypes Using Intravitreal Aflibercept Injection
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