EAGLE: Evaluating Genotypes Using Intravitreal Aflibercept Injection

Phase 4

Completed

Conditions: Macular Degeneration
Wet Macular Degeneration

Interventions: Drug: Intravitreal aflibercept injection

Registration Number: NCT02689518

Lead Sponsor: University of California, San Diego

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 50

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment - On-Label	Intravitreal aflibercept injection	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

Primary Outcome Measures

Name	Time	Method
Anatomic Response	12 Months	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

Name	Time	Method
Visual/Treatment Response	12 Months	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).