Age - Related Macular Degeneration (AMD)
Conditions
Keywords
AMD
Brief summary
This is a phase 4, open-label, single arm, multicenter, clinical study in patients with neovascular AMD designed to evaluate the efficacy and safety of Intravitreal Aflibercept Injection (IAI) administered over 2 years , and to provide clinical information from the first year in the trial evaluating the adverse effects, if any, on the corneal endothelium following administration of IAI.
Interventions
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
include but are not limited to: 1. Men or women great than or equal to 50 years of age with unilateral neovascular AMD 2. BCVA ETDRS letter score of 73 to 24 (20/40 to 20/320) in the study eye 3. Active primary subfoveal choroidal neovascularization (CNV) lesions secondary to AMD, including juxtafoveal lesions that affect the fovea as evidenced by FA in the study eye 4. The CNV area must be at least 50% of total lesion size 5. Willing and able to comply with clinic visits and study-related procedures 6. Provide signed informed consent 7. Provide signed Health Insurance Portability and Accountability Act (HIPAA) authorization
Exclusion criteria
include but are not limited to: 1. Neovascular AMD in the fellow eye 2. Corneal endothelial measures as judged by an independent reading center 3. Any prior use of intraocular anti-VEGF treatment for neovascular AMD in either eye 4. Structural damage to the center of the macula in the study eye that is likely to preclude improvement in BCVA following the resolution of macular edema 5. History of cataract surgery, or other intraocular surgery in either eye, within 1 year of screening 6. History of cataract surgery, or other intraocular surgery in either eye, within 1 year of screening, or yttrium aluminum garnet (YAG) Capsulotomy within 3 months of screening 7. Contact lens wear in either eye within 6 months of screening 8. History of angle closure glaucoma in either eye 9. Intraocular laser therapy including selective laser trabeculoplasty (SLT), YAG, prophylactic peripheral iridotomy (PI) in either eye within 1 year of screening, or YAG Capsulotomy within 3 months of screening 10. History of cataract surgery requiring an anterior chamber intraocular lens implant at any time in either eye 11. Any prior ocular trauma (blunt or penetrating) in either eye 12. Embedded corneal foreign body in either eye 13. Evidence of infectious blepharitis, keratitis, scleritis, or conjunctivitis in either eye 14. Ocular media of insufficient quality to obtain fundus and OCT images in the study eye 15. Any prior ocular inflammation/infection in either eye within 3 months of the screening visit 16. Any prior use of amantadine 17. Significant pre-retinal fibrosis involving the macula in the study eye (where, in the opinion of the investigator, the pre-retinal fibrosis is causing distortion or traction on the central macular region which may be limiting vision, or inducing retinal edema/thickening, beyond that due to underlying CNV) 18. Intraocular pressure (IOP) greater than or equal to 30 mm Hg in the study eye at screening 19. Uncontrolled diabetes mellitus (DM) (HbA1c ≥8) 20. Current treatment with systemic anti-VEGF therapeutics at screening 21. Known serious allergy to the fluorescein sodium for injection in angiography 22. Participation in an investigational study within 30 days prior to the screening visit that involved treatment with any drug (excluding vitamins and minerals) or device. 23. Positive serum hCG pregnancy test at the screening visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score From Baseline to Week 100 - Last Observation Carried Forward (LOCF) | Baseline to Week 100 | Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better vision. LOCF approach was used if any ETDRS letter score was missed after start of treatment, but baseline data were not carried forward. No formal statistical analyses were performed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Whose Optical Coherence Tomography (OCT) Status Was Dry at Week 52 and at Week 100 (LOCF) | Baseline to Week 100 | Retinal fluid status was evaluated using spectral domain OCT on the study eye at every study visit. Last observation carried forward (LOCF) method was used to impute missing data. |
| Percentage of Participants Who Gained ≥15 ETDRS Letters Compared With Baseline at Week 52 and Week 100 (LOCF) | At week 52 and At week 100 | Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better vision. LOCF approach was used if any ETDRS letter score was missed after start of treatment, but baseline data were not carried forward. No formal statistical analyses were performed. |
| Percentage of Participants Who Gained ≥0, ≥5, ≥10, or ≥30 Letters From Baseline in BCVA Through Week 100 (LOCF) | Baseline to Week 100 | Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better functioning. |
| Percentage of Patients Who Lost >0, ≥5, ≥10, or ≥15 Letters From Baseline in BCVA Through Week 100 (LOCF) | Baseline to Week 100 | Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better functioning. |
| Change From Baseline in Best Corrected Visual Acuity Score Through Week 52 (LOCF) | Baseline to Week 52 | Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better vision. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Corneal Endothelial Cell Density (ECD) at Week 24 and Week 52 in the Study Eye and the Fellow Eye - Endothelial Cell Density Evaluable Set (EES) | At week 24 and At week 52 | EES included all eligible patients who were treated in the study eye, untreated in the fellow eye, had baseline specular microscopy image in both eyes, and completed week 52 evaluation in both eyes and treatment with systemic anti-VEGF therapeutics |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 43 sites in the US from 14Nov2012 to 03Sep2015. The target study population consisted of men and women 50 years of age and older with neovascular AMD who met all study eligibility criteria. A total of 288 patients were screened, of whom 154 patients were enrolled and treated. A total of 126 patients completed week 100.
Participants by arm
| Arm | Count |
|---|---|
| Open Label IAI Intravitreal Aflibercept Injection (IAI) | 154 |
| Total | 154 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 8 |
| Overall Study | Death | 3 |
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | Physician Decision | 3 |
| Overall Study | Protocol Deviation | 1 |
| Overall Study | Relocation (did not wish to transfer) | 1 |
| Overall Study | Withdrawal by Subject | 8 |
Baseline characteristics
| Characteristic | Open Label IAI |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 137 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants |
| Best Corrected Visual Acuity (BCVA) in the study eye (Letters Read) | 54.3 letters correctly read STANDARD_DEVIATION 13.47 |
| Central Subfield Thickness in the study eye by Optical Coherence Tomography (OCT) | 420.5 micrometers (μm) STANDARD_DEVIATION 134.9 |
| Corneal Endothelial Cell Density - Endothelial Cell Density Evaluable Set (EES) Fellow eye | 2388.0 cells/mm^2 STANDARD_DEVIATION 383.93 |
| Corneal Endothelial Cell Density - Endothelial Cell Density Evaluable Set (EES) Study eye | 2409.8 cells/mm^2 STANDARD_DEVIATION 363.89 |
| Sex: Female, Male Female | 96 Participants |
| Sex: Female, Male Male | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 38 / 154 |
| serious Total, serious adverse events | 45 / 154 |
Outcome results
Primary
Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score From Baseline to Week 100 - Last Observation Carried Forward (LOCF)
Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better vision. LOCF approach was used if any ETDRS letter score was missed after start of treatment, but baseline data were not carried forward. No formal statistical analyses were performed.
Time frame: Baseline to Week 100
Population: Results are presented for the full analysis set (FAS). FAS included all patients who received at least one dose of study drug in the study eye, had baseline Best Corrected Visual Acuity (BCVA) assessment on the study eye, and had at least one post-baseline BCVA assessment on the study eye.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Open Label IAI | Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score From Baseline to Week 100 - Last Observation Carried Forward (LOCF) | Week 100 | 58.7 letters correctly read | Standard Deviation 20.5 |
| Open Label IAI | Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score From Baseline to Week 100 - Last Observation Carried Forward (LOCF) | Change from Baseline at Week 100 | 4.5 letters correctly read | Standard Deviation 17.2 |
Secondary
Change From Baseline in Best Corrected Visual Acuity Score Through Week 52 (LOCF)
Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better vision.
Time frame: Baseline to Week 52
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Open Label IAI | Change From Baseline in Best Corrected Visual Acuity Score Through Week 52 (LOCF) | At Week 52 | 60.1 Letters correctly read | Standard Deviation 18.94 |
| Open Label IAI | Change From Baseline in Best Corrected Visual Acuity Score Through Week 52 (LOCF) | Change from Baseline at Week 52 | 5.9 Letters correctly read | Standard Deviation 15.54 |
Secondary
Percentage of Participants Who Gained ≥0, ≥5, ≥10, or ≥30 Letters From Baseline in BCVA Through Week 100 (LOCF)
Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better functioning.
Time frame: Baseline to Week 100
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Open Label IAI | Percentage of Participants Who Gained ≥0, ≥5, ≥10, or ≥30 Letters From Baseline in BCVA Through Week 100 (LOCF) | Gained ≥ 0 Letters at Week 100 | 70.9 percentage of participants |
| Open Label IAI | Percentage of Participants Who Gained ≥0, ≥5, ≥10, or ≥30 Letters From Baseline in BCVA Through Week 100 (LOCF) | Gained ≥ 5 Letters at Week 100 | 57.6 percentage of participants |
| Open Label IAI | Percentage of Participants Who Gained ≥0, ≥5, ≥10, or ≥30 Letters From Baseline in BCVA Through Week 100 (LOCF) | Gained ≥10 Letters at Week 100 | 40.4 percentage of participants |
| Open Label IAI | Percentage of Participants Who Gained ≥0, ≥5, ≥10, or ≥30 Letters From Baseline in BCVA Through Week 100 (LOCF) | Gained ≥30 Letters at Week 100 | 4.6 percentage of participants |
Secondary
Percentage of Participants Who Gained ≥15 ETDRS Letters Compared With Baseline at Week 52 and Week 100 (LOCF)
Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better vision. LOCF approach was used if any ETDRS letter score was missed after start of treatment, but baseline data were not carried forward. No formal statistical analyses were performed.
Time frame: At week 52 and At week 100
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Open Label IAI | Percentage of Participants Who Gained ≥15 ETDRS Letters Compared With Baseline at Week 52 and Week 100 (LOCF) | At week 52 | 25.8 percentage of participants |
| Open Label IAI | Percentage of Participants Who Gained ≥15 ETDRS Letters Compared With Baseline at Week 52 and Week 100 (LOCF) | At week 100 | 22.5 percentage of participants |
Secondary
Percentage of Participants Whose Optical Coherence Tomography (OCT) Status Was Dry at Week 52 and at Week 100 (LOCF)
Retinal fluid status was evaluated using spectral domain OCT on the study eye at every study visit. Last observation carried forward (LOCF) method was used to impute missing data.
Time frame: Baseline to Week 100
Population: Full analysis set (FAS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Open Label IAI | Percentage of Participants Whose Optical Coherence Tomography (OCT) Status Was Dry at Week 52 and at Week 100 (LOCF) | Baseline: Dry | 0.7 percentage of participants |
| Open Label IAI | Percentage of Participants Whose Optical Coherence Tomography (OCT) Status Was Dry at Week 52 and at Week 100 (LOCF) | Baseline: Not Dry | 99.3 percentage of participants |
| Open Label IAI | Percentage of Participants Whose Optical Coherence Tomography (OCT) Status Was Dry at Week 52 and at Week 100 (LOCF) | Week 52: Dry | 53.0 percentage of participants |
| Open Label IAI | Percentage of Participants Whose Optical Coherence Tomography (OCT) Status Was Dry at Week 52 and at Week 100 (LOCF) | Week 52: Not Dry | 47.0 percentage of participants |
| Open Label IAI | Percentage of Participants Whose Optical Coherence Tomography (OCT) Status Was Dry at Week 52 and at Week 100 (LOCF) | Week 100: Dry | 51.7 percentage of participants |
| Open Label IAI | Percentage of Participants Whose Optical Coherence Tomography (OCT) Status Was Dry at Week 52 and at Week 100 (LOCF) | Week 100: Not Dry | 48.3 percentage of participants |
Secondary
Percentage of Patients Who Lost >0, ≥5, ≥10, or ≥15 Letters From Baseline in BCVA Through Week 100 (LOCF)
Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better functioning.
Time frame: Baseline to Week 100
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Open Label IAI | Percentage of Patients Who Lost >0, ≥5, ≥10, or ≥15 Letters From Baseline in BCVA Through Week 100 (LOCF) | Lost >0 Letters at Week 100 | 29.1 percentage of participants |
| Open Label IAI | Percentage of Patients Who Lost >0, ≥5, ≥10, or ≥15 Letters From Baseline in BCVA Through Week 100 (LOCF) | Lost ≥5 Letters at Week 100 | 23.2 percentage of participants |
| Open Label IAI | Percentage of Patients Who Lost >0, ≥5, ≥10, or ≥15 Letters From Baseline in BCVA Through Week 100 (LOCF) | Lost ≥10 Letters at Week 100 | 16.6 percentage of participants |
| Open Label IAI | Percentage of Patients Who Lost >0, ≥5, ≥10, or ≥15 Letters From Baseline in BCVA Through Week 100 (LOCF) | Lost ≥15 Letters at Week 100 | 13.2 percentage of participants |
Other Pre-specified
Percent Change From Baseline in Corneal Endothelial Cell Density (ECD) at Week 24 and Week 52 in the Study Eye and the Fellow Eye - Endothelial Cell Density Evaluable Set (EES)
EES included all eligible patients who were treated in the study eye, untreated in the fellow eye, had baseline specular microscopy image in both eyes, and completed week 52 evaluation in both eyes and treatment with systemic anti-VEGF therapeutics
Time frame: At week 24 and At week 52
Population: EES
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Open Label IAI | Percent Change From Baseline in Corneal Endothelial Cell Density (ECD) at Week 24 and Week 52 in the Study Eye and the Fellow Eye - Endothelial Cell Density Evaluable Set (EES) | Week 24: Study eye | -0.3 percent change from baseline | Standard Deviation 4.15 |
| Open Label IAI | Percent Change From Baseline in Corneal Endothelial Cell Density (ECD) at Week 24 and Week 52 in the Study Eye and the Fellow Eye - Endothelial Cell Density Evaluable Set (EES) | Week 24: Fellow eye | 1.0 percent change from baseline | Standard Deviation 4.28 |
| Open Label IAI | Percent Change From Baseline in Corneal Endothelial Cell Density (ECD) at Week 24 and Week 52 in the Study Eye and the Fellow Eye - Endothelial Cell Density Evaluable Set (EES) | Week 52: Study eye | -0.2 percent change from baseline | Standard Deviation 4.19 |
| Open Label IAI | Percent Change From Baseline in Corneal Endothelial Cell Density (ECD) at Week 24 and Week 52 in the Study Eye and the Fellow Eye - Endothelial Cell Density Evaluable Set (EES) | Week 52: Fellow eye | -0.3 percent change from baseline | Standard Deviation 4.04 |