Age-Related Macular Degeneration
Conditions
Keywords
Wet AMD, choroidal neovascularization, Fovista®, E10030, Avastin®, Eylea®
Brief summary
The objectives of this study are to evaluate the safety and efficacy of intravitreal administration of Fovista® administered in combination with either Avastin® or Eylea® compared to Avastin® or Eylea® 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 two arms per study design: * Fovista® 1.5 mg/eye + Avastin® 1.25 mg/eye or Eylea® 2 mg/eye * Fovista® sham + Avastin® 1.25 mg/eye or Eylea® 2 mg/eye Subjects will be treated for up to 24 months with active Fovista® or sham, in combination with either Avastin® or Eylea® with the primary endpoint at 12 months. Approximately 622 subjects will be randomized into one of the two treatment groups (311 patients per dose group), and the efficacy analysis will be based on the data from these two groups as per the SAP
Interventions
DRUGE10030
DRUGbevacizumab or aflibercept
Patients are randomized to receive either bevacizumab or aflibercept
DRUGE10030 sham injection
Pressure on the eye with a syringe with no needle
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 (Measured at Baseline and at the Month 12 Visit) | 12 months | The primary efficacy endpoint is the mean change in visual acuity (ETDRS letters) measured at baseline and at the month 12 visit. Higher ETDRS letters represents higher vision and a higher change in ETDRS letters represents better functioning. |
Countries
Argentina, Australia, Austria, Brazil, Canada, Colombia, Croatia, Czechia, Estonia, Finland, France, Germany, Hungary, Israel, Italy, Latvia, Norway, Poland, Portugal, Slovakia, Spain, United States
Participant flow
Recruitment details
The study was conducted at 214 centers (107 in North America and 107 in the rest of the world) in 22 countries (20 of which enrolled patients) between 19 May 2014 and 15 September 2017.
Pre-assignment details
Three (3) of the 645 patients who were enrolled and randomized did not receive treatments. Remaining 642 subjects were grouped into two treatment groups (E10030 + Eylea/Avastin vs. Sham + Eylea/Avastin) for the purposes of efficacy analyses in accordance with the pre-specified study design, and the SAP.
Participants by arm
| Arm | Count |
|---|---|
| E10030 + Bevacizumab or Aflibercept E10030 1.5 mg intravitreal injection + bevacizumab 1.25 mg intravitreal injection or aflibercept 2 mg intravitreal injection
E10030
bevacizumab or aflibercept: Patients are randomized to receive either bevacizumab or aflibercept | 322 |
| Sham + Bevacizumab or Aflibercept E10030 sham injection + bevacizumab 1.25 mg intravitreal injection or aflibercept 2 mg intravitreal injection
bevacizumab or aflibercept: Patients are randomized to receive either bevacizumab or aflibercept
E10030 sham injection: Pressure on the eye with a syringe with no needle | 320 |
| Total | 642 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Year 1 | Adverse Event | 7 | 6 |
| Year 1 | Death | 5 | 3 |
| Year 1 | Lost to Follow-up | 2 | 1 |
| Year 1 | Physician Decision | 7 | 3 |
| Year 1 | Protocol Violation | 0 | 1 |
| Year 1 | Withdrawal by Subject | 18 | 9 |
| Year 2 | Adverse Event | 8 | 2 |
| Year 2 | Death | 0 | 2 |
| Year 2 | Lost to Follow-up | 1 | 6 |
| Year 2 | Physician Decision | 8 | 1 |
| Year 2 | Sponsor Decision, early termination | 192 | 203 |
| Year 2 | Withdrawal by Subject | 8 | 8 |
Baseline characteristics
| Characteristic | E10030 + Bevacizumab or Aflibercept | Total | Sham + Bevacizumab or Aflibercept |
|---|---|---|---|
| Age, Continuous | 76.5 years STANDARD_DEVIATION 8.36 | 76.6 years STANDARD_DEVIATION 8.36 | 76.6 years STANDARD_DEVIATION 8.36 |
| Age, Customized Age Adults 18-64 years | 31 Participants | 56 Participants | 25 Participants |
| Age, Customized Age Adults 65-84 years | 239 Participants | 478 Participants | 239 Participants |
| Age, Customized Age Adults 85 years and over | 52 Participants | 108 Participants | 56 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 28 Participants | 51 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 294 Participants | 591 Participants | 297 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Argentina | 4 Participants | 8 Participants | 4 Participants |
| Region of Enrollment Australia | 2 Participants | 5 Participants | 3 Participants |
| Region of Enrollment Austria | 2 Participants | 5 Participants | 3 Participants |
| Region of Enrollment Brazil | 3 Participants | 6 Participants | 3 Participants |
| Region of Enrollment Canada | 1 Participants | 2 Participants | 1 Participants |
| Region of Enrollment Colombia | 7 Participants | 12 Participants | 5 Participants |
| Region of Enrollment Croatia | 22 Participants | 43 Participants | 21 Participants |
| Region of Enrollment Czechia | 15 Participants | 29 Participants | 14 Participants |
| Region of Enrollment Estonia | 9 Participants | 16 Participants | 7 Participants |
| Region of Enrollment France | 26 Participants | 49 Participants | 23 Participants |
| Region of Enrollment Hungary | 48 Participants | 98 Participants | 50 Participants |
| Region of Enrollment Israel | 32 Participants | 60 Participants | 28 Participants |
| Region of Enrollment Italy | 28 Participants | 57 Participants | 29 Participants |
| Region of Enrollment Latvia | 8 Participants | 15 Participants | 7 Participants |
| Region of Enrollment Poland | 1 Participants | 4 Participants | 3 Participants |
| Region of Enrollment Portugal | 9 Participants | 21 Participants | 12 Participants |
| Region of Enrollment Slovakia | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment Spain | 10 Participants | 20 Participants | 10 Participants |
| Region of Enrollment United States | 92 Participants | 187 Participants | 95 Participants |
| Sex: Female, Male Female | 178 Participants | 370 Participants | 192 Participants |
| Sex: Female, Male Male | 144 Participants | 272 Participants | 128 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 322 | 6 / 320 |
| other Total, other adverse events | 105 / 322 | 107 / 320 |
| serious Total, serious adverse events | 58 / 322 | 32 / 320 |
Outcome results
Primary
Mean Change in Visual Acuity (Measured at Baseline and at the Month 12 Visit)
The primary efficacy endpoint is the mean change in visual acuity (ETDRS letters) measured at baseline and at the month 12 visit. Higher ETDRS letters represents higher vision and a higher change in ETDRS letters represents better functioning.
Time frame: 12 months
Population: As pre-specified in the SAP and per the study design, 2 treatment groups (E10030 +Eylea/Avastin vs. Sham + Eylea/Avastin) will be compared. All 642 subjects who received at least one dose of the study drug, irrespective of the dose received, were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| E10030 + Bevacizumab or Aflibercept | Mean Change in Visual Acuity (Measured at Baseline and at the Month 12 Visit) | 9.42 letters | Standard Error 0.85 |
| Sham + Bevacizumab or Aflibercept | Mean Change in Visual Acuity (Measured at Baseline and at the Month 12 Visit) | 9.04 letters | Standard Error 0.85 |