Macular Degeneration, Wet Macular Degeneration
Conditions
Keywords
AMD, Wet AMD, Macular degeneration, Wet macular degeneration, Neovascularization, Retina, Retinal degeneration
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.
Interventions
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.
Sponsors
Regeneron Pharmaceuticals
University of California, San Diego
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to 90 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
The record for one participant was lost so we will report on 49/50.
Participants by arm
| Arm | Count |
|---|---|
| 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
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. | 49 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Treatment - On-Label |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 47 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 43 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 0 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
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.
Time frame: 12 Months
Population: Principal Investigator is no longer associated with the institution. All efforts were exhausted to obtain the data but no data could be found.
Secondary
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).
Time frame: 12 Months
Population: Principal Investigator is no longer associated with the institution. All efforts were exhausted to obtain the data but no data could be found.
Other Pre-specified
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.
Time frame: 12 Months
Population: Principal Investigator is no longer associated with the institution. All efforts were exhausted to obtain the data but no data could be found.