EAGLE: Evaluating Genotypes Using Intravitreal Aflibercept Injection

• Sponsor: University of California, San Diego (Other)
• Overall Status: Completed
• CT.gov ID: NCT02689518
• Collaborator: Regeneron Pharmaceuticals (Industry)
• Enrollment: 50
• Location: 1
• Arm: 1
• Actual Duration (Months): 67.4
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Macular Degeneration; Wet Macular Degeneration	Drug: Intravitreal aflibercept injection	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Clinical and Genetic Assessment of Treatment Response in Patients With Age-related Macular Degeneration Using Intravitreal Aflibercept Injection
• Actual Study Start Date: Apr 1, 2014
• Actual Primary Completion Date: Nov 12, 2019
• Actual Study Completion Date: Nov 12, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

1. 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).

Other Outcome Measures

1. Safety - Incidence and Severity of Ocular and Non-ocular Adverse Events [12 Months]

   Incidence and severity of ocular and non-ocular adverse events using Aflibercept intravitreal injections will also be evaluated.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Shiley Eye Center	La Jolla	California	United States	92126

Sponsors and Collaborators

• University of California, San Diego
• Regeneron Pharmaceuticals

Investigators

• Principal Investigator: Michael Goldbaum, M.D., UCSD

Study Documents (Full-Text)

• Study Protocol - Feb 21, 2019

More Information

Publications

None provided.

• Responsible Party: Michael Goldbaum, MD, Professor of Ophthalmology in Residence, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT02689518
• Other Study ID Numbers: EAGLE
• First Posted: Feb 24, 2016
• Last Update Posted: Mar 25, 2021
• Last Verified: Mar 1, 2021

• Keywords provided by Michael Goldbaum, MD, Professor of Ophthalmology in Residence, University of California, San Diego: AMD; Wet AMD; Macular degeneration; Wet macular degeneration; Neovascularization; Retina; Retinal degeneration
• Additional relevant MeSH terms: Macular Degeneration; Wet Macular Degeneration; Aflibercept

Study Results

Participant Flow

Recruitment Details	The record for one participant was lost so we will report on 49/50.

Arm/Group Title	Treatment - On-Label
Arm/Group 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 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.
Period Title: Overall Study
STARTED	49
COMPLETED	46
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Treatment - On-Label
Arm/Group 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 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.
Overall Participants	49
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 4.1%
>=65 years	47 95.9%
Sex: Female, Male (Count of Participants)
Female	21 42.9%
Male	28 57.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 8.2%
Not Hispanic or Latino	43 87.8%
Unknown or Not Reported	2 4.1%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Principal Investigator is no longer associated with the institution. All efforts were exhausted to obtain the data but no data could be found.

Arm/Group Title	Treatment - On-Label
Arm/Group 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 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.
Measure Participants	0

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Principal Investigator is no longer associated with the institution. All efforts were exhausted to obtain the data but no data could be found.

Arm/Group Title	Treatment - On-Label
Arm/Group 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 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.
Measure Participants	0

3. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

Principal Investigator is no longer associated with the institution. All efforts were exhausted to obtain the data but no data could be found.

Arm/Group Title	Treatment - On-Label
Arm/Group 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 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.
Measure Participants	0

Adverse Events

Time Frame	1 year
Adverse Event Reporting Description	Principal Investigator is no longer associated with the institution. All efforts were exhausted to obtain the data but no data could be found.
Arm/Group Title	Treatment - On-Label
Arm/Group 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 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.
All Cause Mortality
	Treatment - On-Label
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Serious Adverse Events
	Treatment - On-Label
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Treatment - On-Label
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

Principal Investigator is no longer associated with the institution. All efforts were exhausted to obtain the data but no data could be found.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.