EAGLE: Evaluating Genotypes Using Intravitreal Aflibercept Injection (EAGLE)

Clinical and Genetic Assessment of Treatment Response in Patients With Age-related Macular Degeneration Using Intravitreal Aflibercept Injection

Clinical and genetic evaluation of individuals treated with intravitreal aflibercept injection (Eylea) for neovascular age-related macular degeneration (wet AMD)

Study Overview

• Status: Completed
• Conditions: Macular Degeneration; Wet Macular Degeneration
• Intervention / Treatment: Drug: Intravitreal aflibercept injection

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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92126
      • Shiley Eye Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 50 years
2. Naïve neovascular wet-AMD (has not received treatment before)
3. Willing and able to comply with clinic visits and study-related procedures
4. Provide signed informed consent

Exclusion Criteria:

1. Previous therapy in study eye for AMD or other retinal disease which may be used in the treatment of AMD
2. Previous subfoveal focal laser photocoagulation involving the foveal center in the study eye
3. History of vitrectomy, submacular surgery, or other surgical intervention for AMD in the study eye
4. 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
5. Active intraocular inflammation (grade trace or above) in the study eye, or history of idiopathic or autoimmune-associated uveitis in either eye
6. Current vitreous hemorrhage in the study eye
7. History of rhegmatogenous retinal detachment or macular hole (Stage 3 or 4) in the study eye
8. Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye
9. Aphakia, ACIOL, or unstable PCIOL
10. Uncontrolled glaucoma in the study eye (defined as intraocular pressure ≥30 mmHg despite treatment with anti-glaucoma medication)
11. Pregnant or breast-feeding women
12. 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)
13. 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 Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Treatment - On-Label; 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	Drug: Intravitreal aflibercept injection; 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.; Other Names: Eylea

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	12 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	12 Months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety - Incidence and Severity of Ocular and Non-ocular Adverse Events	Incidence and severity of ocular and non-ocular adverse events using Aflibercept intravitreal injections will also be evaluated.	12 Months

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Collaborators: Regeneron Pharmaceuticals
• Investigators: Principal Investigator: Michael Goldbaum, M.D., UCSD

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2014
• Primary Completion (Actual): November 12, 2019
• Study Completion (Actual): November 12, 2019

Study Registration Dates

• First Submitted: April 21, 2014
• First Submitted That Met QC Criteria: February 23, 2016
• First Posted (Estimate): February 24, 2016

Study Record Updates

• Last Update Posted (Actual): March 25, 2021
• Last Update Submitted That Met QC Criteria: March 23, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Retina; AMD; Wet AMD; Macular degeneration; Neovascularization; Retinal degeneration; Wet macular degeneration
• 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: EAGLE