Age-Related Macular Degeneration
Conditions
Keywords
Wet AMD, choroidal neovascularization, Fovista®, E10030, Lucentis®
Brief summary
The objectives of this study are to evaluate the safety and efficacy of intravitreal administration of Fovista® administered in combination with Lucentis® compared to Lucentis® monotherapy in subjects with subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD).
Detailed description
Subjects will be randomized in a 1:1 ratio to the following dose groups: * Fovista® 1.5 mg/eye + Lucentis® 0.5 mg/eye * Fovista® sham + Lucentis® 0.5 mg/eye Subjects will be treated for a total of 24 months with active Fovista® or sham in combination with Lucentis® with the primary endpoint at 12 months. Primary Efficacy Endpoint: The primary efficacy endpoint is the mean change in visual acuity (ETDRS letters) from baseline at the month 12 visit. Safety Endpoints: Safety endpoints include adverse events, vital signs, ophthalmic variables \[ophthalmic examination, intraocular pressure (IOP), fluorescein angiogram (FA), optical coherence tomography (OCT)\], ECG, and laboratory variables. Approximately 622 subjects will be randomized into one of the two treatment cohorts (311 patients per dose group).
Interventions
Sponsors
Ophthotech Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects of either gender aged ≥ 50 years * Active subfoveal choroidal neovascularization (CNV) secondary to AMD * Presence of sub-retinal hyper-reflective material (SD-OCT)
Exclusion criteria
* Any prior treatment for AMD in the study eye prior to the Day 1 visit, except oral supplements of vitamins and minerals * Any prior intravitreal treatment in the study eye prior to the Day 1 visit, regardless of indication (including intravitreal corticosteroids) * Any intraocular surgery or thermal laser within three (3) months of trial entry. Any prior thermal laser in the macular region, regardless of indication * Subjects with subfoveal scar or subfoveal atrophy are excluded * Diabetes mellitus
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Visual Acuity From Baseline to 12 Months | 12 Months | The primary efficacy endpoint is the mean change in visual acuity (ETDRS letters) from baseline to the month 12 visit. Higher ETDRS letters represents higher vision and a higher change in ETDRS letters represents better functioning. |
Countries
Austria, Belgium, Brazil, Canada, Czechia, Estonia, Italy, Latvia, Poland, Slovakia, Switzerland, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| E10030 + Ranibizumab E10030 1.5 mg intravitreal injection + ranibizumab 0.5 mg intravitreal injection
E10030
ranibizumab | 309 |
| Sham + Ranibizumab E10030 sham intravitreal injection + ranibizumab 0.5 mg intravitreal injection
ranibizumab
E10030 sham intravitreal injection: Pressure on the eye with a syringe with no needle | 310 |
| Total | 619 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 5 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Physician Decision | 2 | 2 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Subject non-compliance | 0 | 3 |
| Overall Study | Withdrawal by Subject | 9 | 17 |
Baseline characteristics
| Characteristic | E10030 + Ranibizumab | Total | Sham + Ranibizumab |
|---|---|---|---|
| Age, Continuous | 76.1 years STANDARD_DEVIATION 7.98 | NA years | 76.9 years STANDARD_DEVIATION 8.04 |
| Age, Customized 85 years and over | 40 Participants | 97 Participants | 57 Participants |
| Age, Customized Adults 18-64 years | 26 Participants | 46 Participants | 20 Participants |
| Age, Customized Adults 65 - 84 years | 243 Participants | 476 Participants | 233 Participants |
| Region of Enrollment Austria | 5 Participants | 10 Participants | 5 Participants |
| Region of Enrollment Belgium | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment Brazil | 8 Participants | 16 Participants | 8 Participants |
| Region of Enrollment Canada | 14 Participants | 23 Participants | 9 Participants |
| Region of Enrollment Czechia | 42 Participants | 84 Participants | 42 Participants |
| Region of Enrollment Estonia | 12 Participants | 22 Participants | 10 Participants |
| Region of Enrollment Italy | 56 Participants | 118 Participants | 62 Participants |
| Region of Enrollment Latvia | 21 Participants | 46 Participants | 25 Participants |
| Region of Enrollment Poland | 23 Participants | 46 Participants | 23 Participants |
| Region of Enrollment Slovakia | 5 Participants | 9 Participants | 4 Participants |
| Region of Enrollment Switzerland | 3 Participants | 7 Participants | 4 Participants |
| Region of Enrollment United Kingdom | 13 Participants | 27 Participants | 14 Participants |
| Region of Enrollment United States | 106 Participants | 210 Participants | 104 Participants |
| Sex: Female, Male Female | 181 Participants | 377 Participants | 196 Participants |
| Sex: Female, Male Male | 128 Participants | 242 Participants | 114 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 6 / 310 | 2 / 309 |
| other Total, other adverse events | 123 / 310 | 114 / 309 |
| serious Total, serious adverse events | 48 / 310 | 36 / 309 |
Outcome results
Primary
Mean Change in Visual Acuity From Baseline to 12 Months
The primary efficacy endpoint is the mean change in visual acuity (ETDRS letters) from baseline to the month 12 visit. Higher ETDRS letters represents higher vision and a higher change in ETDRS letters represents better functioning.
Time frame: 12 Months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| E10030 + Ranibizumab | Mean Change in Visual Acuity From Baseline to 12 Months | 10.74 letters | Standard Error 0.86 |
| Sham + Ranibizumab | Mean Change in Visual Acuity From Baseline to 12 Months | 9.82 letters | Standard Error 0.86 |