Exudative Age-Related Macular Degeneration
Conditions
Keywords
Age-Related Macular Degeneration, Wet, Exudative, AMD, Intravitreal injection, Retina
Brief summary
The purpose of this study is to compare the efficacy and safety of ESBA1008 versus EYLEA® in the treatment of exudative age-related macular degeneration.
Detailed description
This study consisted of 16 visits (Screening, Baseline \[Day 0\], and 14 post-baseline assessment visits) that occurred at 4-week intervals through Week 56. Enrolled subjects were randomized 1:1 to receive ESBA1008 or EYLEA. All subjects received active intravitreal (IVT) injections at baseline with 2 additional loading doses of the assigned investigational product at 4-week intervals (ie, at Weeks 4 and 8) and then received further injections at 8-weeks intervals at Weeks 16, 24, and 32. Subjects in the ESBA1008 group also received an injection at Week 44, while subjects in the EYLEA group also received injections at Weeks 40 and 48. To maintain the study masking, subjects in the ESBA1008 group received sham injections at Weeks 40 and 48 (when the subjects in the EYLEA group received active injections), while subjects in the EYLEA group received a sham injection at Week 44 (when the subjects in the ESBA1008 group received an active injection). All subjects were followed up to Week 56. Week 40 visit was the end of assessment period for the 8-week treatment cycle.
Interventions
For intravitreal (IVT) injection
DRUGAflibercept
For intravitreal (IVT) injection
Sponsors
Alcon Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Give written informed consent; be able to make the required study visits and follow instructions. * Diagnosis of wet age-related macular degeneration, as specified in protocol. * Best-corrected visual acuity (BCVA) as specified in protocol * Other protocol-specified inclusion criteria may apply.
Exclusion criteria
* Either eye: Any active ocular or periocular infection or active intraocular inflammation. * Study eye: Any approved or investigational treatment for exudative AMD other than vitamin supplements. * Study eye: Any current or history of macular or retinal disease other than exudative AMD. * Study eye: Any concurrent intraocular condition that, in the opinion of the Investigator, could require medical or surgical intervention during the course of the study to prevent or treat vision loss, or that limits the potential to gain visual acuity with the investigational product. * Study eye: Uncontrolled glaucoma. * Study eye: Any ocular disease that, in the opinion of the Investigator, could compromise the visual acuity. * Study eye: History of eye surgery, as specified in protocol. * Study eye: Use of corticosteroids, as specified in protocol. * Any medical condition that, in the opinion of the Investigator, would preclude scheduled study visits, completion of the study or safe administration of investigational product. * Any screening laboratory result that, in the opinion of the Investigator, would make the patient unsuitable for study participation. * History of hypersensitivity to any component used in the study, as assessed by the Investigator. * Women of childbearing potential: Lactating, pregnant, plan to become pregnant, or not using adequate birth control, as specified in protocol. * Participation in an investigational drug or device study within time period specified in protocol. * Other protocol-defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best-Corrected Visual Acuity (BCVA) Change From Baseline (No. of Letters) to Week 12 | Baseline (Day 0), Week 12 | This outcome measure was used to compare the ESBA1008 and EYLEA groups in regards to fluctuations in treatment effect during the maintenance phase with 8-week treatment cycles (ie, to evaluate treatment effect stability during the maintenance phase). BCVA (with spectacles or other visual corrective devices) using Early Treatment Diabetic Retinopathy Study (ETDRS) testing was reported in letters read correctly. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. One eye (study eye) contributed to the analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| BCVA Change From Baseline (No. of Letters) by Visit | Baseline (Day 0), Week 4, Week 8, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56 | BCVA (with spectacles or other visual corrective devices) using ETDRS testing was reported in letters read correctly. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. One eye (study eye) contributed to the analysis. |
| Average BCVA Change From Baseline (No. of Letters) Over the Periods of Week 4 to Week 16, Week 4 to Week 24, Week 4 to Week 40, and Week 4 to Week 56 | Baseline (Day 0), Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56 | The purpose of this outcome measure was to assess the integrated effect of the treatment for different study periods and to provide more robust estimate of the absolute treatment effects. BCVA (with spectacles or other visual corrective devices) using ETDRS testing was reported in letters read correctly. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. These changes were computed as the average of the changes from baseline to each monthly study visit corresponding to each period. One eye (study eye) contributed to the analysis. |
| Average BCVA Change From Week 12 (No. of Letters) Over the Periods of Week 16 to Week 24, Week 16 Week 40, and Week 16 to Week 56 | Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56 | The purpose of this outcome measure was to assess the average maintenance level of BCVA following the 3 loading treatments (ie, after Week 12). BCVA (with spectacles or other visual corrective devices) using ETDRS testing was reported in letters read correctly. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. These changes were computed as the average of the changes from Week 12 to each monthly study visit corresponding to each period. One eye (study eye) contributed to the analysis. |
| BCVA Change From Baseline (No. of Letters) to Week 16 | Baseline (Day 0), Week 16 | BCVA (with spectacles or other visual corrective devices) using ETDRS testing was reported in letters read correctly. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. One eye (study eye) contributed to the analysis. |
| One-Month BCVA Changes (No. of Letters) Following Treatment by Visit | Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52 | The purpose of this outcome measure was to assess the potential treatment needs present at these treatment visits. BCVA (with spectacles or other visual corrective devices) using ETDRS testing was reported in letters read correctly. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. One eye (study eye) contributed to the analysis. |
| Two-Months BCVA Changes (No. of Letters) Following No Treatment for 1 Month in ESBA Treatment Group | Week 36, Week 44, Week 48, Week 56 | BCVA (with spectacles or other visual corrective devices) using ETDRS testing was reported in letters read correctly. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. This outcome measure was pre-specified for ESBA1008 arm only. One eye (study eye) contributed to the analysis. |
| Central Subfield Thickness (CSFT) Change From Baseline by Visit | Baseline (Day 0), Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56 | CSFT (average thickness in the central subfield centered at the fovea) as measured using Spectral-Domain Optical Coherence Tomography (SD-OCT). Reduction in CSFT measurement from baseline indicates improvement. One eye (study eye) contributed to the analysis. |
| One-Month BCVA Changes (No. of Letters) Following No Treatment for 1-Month | Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56 | The purpose of this outcome measure was to assess the stability of BCVA during the second month of 8-week/12-week treatment cycles and specifically to identify potential under treatment. BCVA (with spectacles or other visual corrective devices) using ETDRS testing was reported in letters read correctly. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. One eye (study eye) contributed to the analysis. |
Participant flow
Recruitment details
Subjects were recruited from 41 investigational centers located in the US.
Pre-assignment details
Of the 173 enrolled, 83 subjects were exited as screen failures prior to randomization. One randomized subject did not receive treatment. Another subject randomized to ESBA 1008 received EYLEA treatment. This reporting group includes all randomized and treated subjects, as treated (ESBA1008: 44 subjects and EYLEA: 45 subjects).
Participants by arm
| Arm | Count |
|---|---|
| ESBA1008 ESBA1008 solution, 7 intravitreal (IVT) injections, as specified in protocol | 44 |
| EYLEA Aflibercept, 8 intravitreal (IVT) injections, as specified in protocol | 45 |
| Total | 89 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | ESBA1008 | EYLEA | Total |
|---|---|---|---|
| Age, Continuous | 78.8 years STANDARD_DEVIATION 9.7 | 77.3 years STANDARD_DEVIATION 9.1 | 78.0 years STANDARD_DEVIATION 9.4 |
| Sex: Female, Male Female | 28 Participants | 25 Participants | 53 Participants |
| Sex: Female, Male Male | 16 Participants | 20 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 173 | 22 / 44 | 25 / 45 |
| serious Total, serious adverse events | 0 / 173 | 11 / 44 | 9 / 45 |
Outcome results
Primary
Best-Corrected Visual Acuity (BCVA) Change From Baseline (No. of Letters) to Week 12
This outcome measure was used to compare the ESBA1008 and EYLEA groups in regards to fluctuations in treatment effect during the maintenance phase with 8-week treatment cycles (ie, to evaluate treatment effect stability during the maintenance phase). BCVA (with spectacles or other visual corrective devices) using Early Treatment Diabetic Retinopathy Study (ETDRS) testing was reported in letters read correctly. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. One eye (study eye) contributed to the analysis.
Time frame: Baseline (Day 0), Week 12
Population: This analysis population includes all subjects who were randomized, received at least 1 treatment, had a baseline value, and had at least 1 postbaseline measurement of the primary efficacy variable, BCVA. Subjects were analyzed according to the actual treatment received with LOCF imputation of missing values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ESBA1008 | Best-Corrected Visual Acuity (BCVA) Change From Baseline (No. of Letters) to Week 12 | Baseline (Day 0) | 54.1 letters | Standard Deviation 13.9 |
| ESBA1008 | Best-Corrected Visual Acuity (BCVA) Change From Baseline (No. of Letters) to Week 12 | Change from baseline | 5.8 letters | Standard Deviation 12.7 |
| EYLEA | Best-Corrected Visual Acuity (BCVA) Change From Baseline (No. of Letters) to Week 12 | Baseline (Day 0) | 55.6 letters | Standard Deviation 12.3 |
| EYLEA | Best-Corrected Visual Acuity (BCVA) Change From Baseline (No. of Letters) to Week 12 | Change from baseline | 6.9 letters | Standard Deviation 9.3 |
Comparison: An analysis of variance (ANOVA) model with treatment and baseline BCVA categories (\< 55 and ≥ 55 letters) as class variables was used to estimate the treatment group differences (ESBA1008 - EYLEA) in the primary efficacy endpoint, BCVA Change from baseline to Week 12.80% CI: [-4.19, 1.93]
Secondary
Average BCVA Change From Baseline (No. of Letters) Over the Periods of Week 4 to Week 16, Week 4 to Week 24, Week 4 to Week 40, and Week 4 to Week 56
The purpose of this outcome measure was to assess the integrated effect of the treatment for different study periods and to provide more robust estimate of the absolute treatment effects. BCVA (with spectacles or other visual corrective devices) using ETDRS testing was reported in letters read correctly. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. These changes were computed as the average of the changes from baseline to each monthly study visit corresponding to each period. One eye (study eye) contributed to the analysis.
Time frame: Baseline (Day 0), Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56
Population: This analysis population includes all subjects who were randomized, received at least 1 treatment, had a baseline value, and had at least 1 postbaseline measurement of the primary efficacy variable, BCVA. Subjects were analyzed according to the actual treatment received with LOCF imputation of missing values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ESBA1008 | Average BCVA Change From Baseline (No. of Letters) Over the Periods of Week 4 to Week 16, Week 4 to Week 24, Week 4 to Week 40, and Week 4 to Week 56 | Avg Change from baseline over period of Weeks 4-16 | 5.7 letters | Standard Deviation 11 |
| ESBA1008 | Average BCVA Change From Baseline (No. of Letters) Over the Periods of Week 4 to Week 16, Week 4 to Week 24, Week 4 to Week 40, and Week 4 to Week 56 | Avg Change from baseline over period of Weeks 4-40 | 6.5 letters | Standard Deviation 12.3 |
| ESBA1008 | Average BCVA Change From Baseline (No. of Letters) Over the Periods of Week 4 to Week 16, Week 4 to Week 24, Week 4 to Week 40, and Week 4 to Week 56 | Avg Change from baseline over period of Weeks 4-24 | 6.2 letters | Standard Deviation 11.7 |
| ESBA1008 | Average BCVA Change From Baseline (No. of Letters) Over the Periods of Week 4 to Week 16, Week 4 to Week 24, Week 4 to Week 40, and Week 4 to Week 56 | Avg Change from baseline over period of Weeks 4-56 | 6.4 letters | Standard Deviation 13.3 |
| ESBA1008 | Average BCVA Change From Baseline (No. of Letters) Over the Periods of Week 4 to Week 16, Week 4 to Week 24, Week 4 to Week 40, and Week 4 to Week 56 | Baseline (Day 0) | 54.1 letters | Standard Deviation 13.9 |
| EYLEA | Average BCVA Change From Baseline (No. of Letters) Over the Periods of Week 4 to Week 16, Week 4 to Week 24, Week 4 to Week 40, and Week 4 to Week 56 | Avg Change from baseline over period of Weeks 4-56 | 6.6 letters | Standard Deviation 10 |
| EYLEA | Average BCVA Change From Baseline (No. of Letters) Over the Periods of Week 4 to Week 16, Week 4 to Week 24, Week 4 to Week 40, and Week 4 to Week 56 | Baseline (Day 0) | 55.6 letters | Standard Deviation 12.3 |
| EYLEA | Average BCVA Change From Baseline (No. of Letters) Over the Periods of Week 4 to Week 16, Week 4 to Week 24, Week 4 to Week 40, and Week 4 to Week 56 | Avg Change from baseline over period of Weeks 4-16 | 6.1 letters | Standard Deviation 8 |
| EYLEA | Average BCVA Change From Baseline (No. of Letters) Over the Periods of Week 4 to Week 16, Week 4 to Week 24, Week 4 to Week 40, and Week 4 to Week 56 | Avg Change from baseline over period of Weeks 4-24 | 6.6 letters | Standard Deviation 8.4 |
| EYLEA | Average BCVA Change From Baseline (No. of Letters) Over the Periods of Week 4 to Week 16, Week 4 to Week 24, Week 4 to Week 40, and Week 4 to Week 56 | Avg Change from baseline over period of Weeks 4-40 | 6.5 letters | Standard Deviation 9.2 |
Secondary
Average BCVA Change From Week 12 (No. of Letters) Over the Periods of Week 16 to Week 24, Week 16 Week 40, and Week 16 to Week 56
The purpose of this outcome measure was to assess the average maintenance level of BCVA following the 3 loading treatments (ie, after Week 12). BCVA (with spectacles or other visual corrective devices) using ETDRS testing was reported in letters read correctly. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. These changes were computed as the average of the changes from Week 12 to each monthly study visit corresponding to each period. One eye (study eye) contributed to the analysis.
Time frame: Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56
Population: This analysis population includes all subjects who were randomized, received at least 1 treatment, had a baseline value, and had at least 1 postbaseline measurement of the primary efficacy variable, BCVA. Subjects were analyzed according to the actual treatment received with LOCF imputation of missing values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ESBA1008 | Average BCVA Change From Week 12 (No. of Letters) Over the Periods of Week 16 to Week 24, Week 16 Week 40, and Week 16 to Week 56 | Week 12 | 59.8 letters | Standard Deviation 18.5 |
| ESBA1008 | Average BCVA Change From Week 12 (No. of Letters) Over the Periods of Week 16 to Week 24, Week 16 Week 40, and Week 16 to Week 56 | Avg Change from Week 12 over period Weeks 16-24 | 1.1 letters | Standard Deviation 5.4 |
| ESBA1008 | Average BCVA Change From Week 12 (No. of Letters) Over the Periods of Week 16 to Week 24, Week 16 Week 40, and Week 16 to Week 56 | Avg Change from Week 12 over period Weeks 16-40 | 1.1 letters | Standard Deviation 6.3 |
| ESBA1008 | Average BCVA Change From Week 12 (No. of Letters) Over the Periods of Week 16 to Week 24, Week 16 Week 40, and Week 16 to Week 56 | Avg Change from Week 12 over period Weeks 16-56 | 0.8 letters | Standard Deviation 7 |
| EYLEA | Average BCVA Change From Week 12 (No. of Letters) Over the Periods of Week 16 to Week 24, Week 16 Week 40, and Week 16 to Week 56 | Avg Change from Week 12 over period Weeks 16-56 | -0.0 letters | Standard Deviation 8.1 |
| EYLEA | Average BCVA Change From Week 12 (No. of Letters) Over the Periods of Week 16 to Week 24, Week 16 Week 40, and Week 16 to Week 56 | Week 12 | 62.4 letters | Standard Deviation 16.1 |
| EYLEA | Average BCVA Change From Week 12 (No. of Letters) Over the Periods of Week 16 to Week 24, Week 16 Week 40, and Week 16 to Week 56 | Avg Change from Week 12 over period Weeks 16-40 | -0.1 letters | Standard Deviation 7.3 |
| EYLEA | Average BCVA Change From Week 12 (No. of Letters) Over the Periods of Week 16 to Week 24, Week 16 Week 40, and Week 16 to Week 56 | Avg Change from Week 12 over period Weeks 16-24 | 0.5 letters | Standard Deviation 4.7 |
Secondary
BCVA Change From Baseline (No. of Letters) by Visit
BCVA (with spectacles or other visual corrective devices) using ETDRS testing was reported in letters read correctly. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. One eye (study eye) contributed to the analysis.
Time frame: Baseline (Day 0), Week 4, Week 8, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56
Population: This analysis population includes all subjects who were randomized, received at least 1 treatment, had a baseline value, and had at least 1 postbaseline measurement of the primary efficacy variable, BCVA. Subjects were analyzed according to the actual treatment received with LOCF imputation of missing values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ESBA1008 | BCVA Change From Baseline (No. of Letters) by Visit | Change from baseline at Week 48 | 6.2 letters | Standard Deviation 16.5 |
| ESBA1008 | BCVA Change From Baseline (No. of Letters) by Visit | Baseline (Day 0) | 54.1 letters | Standard Deviation 13.9 |
| ESBA1008 | BCVA Change From Baseline (No. of Letters) by Visit | Change from baseline at Week 4 | 4.8 letters | Standard Deviation 9.1 |
| ESBA1008 | BCVA Change From Baseline (No. of Letters) by Visit | Change from baseline at Week 8 | 6.0 letters | Standard Deviation 11.6 |
| ESBA1008 | BCVA Change From Baseline (No. of Letters) by Visit | Change from baseline at Week 20 | 7.5 letters | Standard Deviation 14.5 |
| ESBA1008 | BCVA Change From Baseline (No. of Letters) by Visit | Change from baseline at Week 24 | 7.1 letters | Standard Deviation 13 |
| ESBA1008 | BCVA Change From Baseline (No. of Letters) by Visit | Change from baseline at Week 28 | 8.3 letters | Standard Deviation 12.2 |
| ESBA1008 | BCVA Change From Baseline (No. of Letters) by Visit | Change from baseline at Week 32 | 6.7 letters | Standard Deviation 13.7 |
| ESBA1008 | BCVA Change From Baseline (No. of Letters) by Visit | Change from baseline at Week 36 | 6.2 letters | Standard Deviation 16.2 |
| ESBA1008 | BCVA Change From Baseline (No. of Letters) by Visit | Change from baseline at Week 40 | 6.3 letters | Standard Deviation 14.9 |
| ESBA1008 | BCVA Change From Baseline (No. of Letters) by Visit | Change from baseline at Week 44 | 7.0 letters | Standard Deviation 15.6 |
| ESBA1008 | BCVA Change From Baseline (No. of Letters) by Visit | Change from baseline at Week 52 | 6.0 letters | Standard Deviation 16.4 |
| ESBA1008 | BCVA Change From Baseline (No. of Letters) by Visit | Change from baseline at Week 56 | 4.9 letters | Standard Deviation 17.9 |
| EYLEA | BCVA Change From Baseline (No. of Letters) by Visit | Change from baseline at Week 44 | 6.5 letters | Standard Deviation 12 |
| EYLEA | BCVA Change From Baseline (No. of Letters) by Visit | Change from baseline at Week 32 | 6.5 letters | Standard Deviation 12.7 |
| EYLEA | BCVA Change From Baseline (No. of Letters) by Visit | Baseline (Day 0) | 55.6 letters | Standard Deviation 12.3 |
| EYLEA | BCVA Change From Baseline (No. of Letters) by Visit | Change from baseline at Week 48 | 6.8 letters | Standard Deviation 13.4 |
| EYLEA | BCVA Change From Baseline (No. of Letters) by Visit | Change from baseline at Week 4 | 4.3 letters | Standard Deviation 7.4 |
| EYLEA | BCVA Change From Baseline (No. of Letters) by Visit | Change from baseline at Week 36 | 6.4 letters | Standard Deviation 13.1 |
| EYLEA | BCVA Change From Baseline (No. of Letters) by Visit | Change from baseline at Week 8 | 6.5 letters | Standard Deviation 8.5 |
| EYLEA | BCVA Change From Baseline (No. of Letters) by Visit | Change from baseline at Week 56 | 7.3 letters | Standard Deviation 13.4 |
| EYLEA | BCVA Change From Baseline (No. of Letters) by Visit | Change from baseline at Week 20 | 7.3 letters | Standard Deviation 9.4 |
| EYLEA | BCVA Change From Baseline (No. of Letters) by Visit | Change from baseline at Week 40 | 5.7 letters | Standard Deviation 13.6 |
| EYLEA | BCVA Change From Baseline (No. of Letters) by Visit | Change from baseline at Week 24 | 8.2 letters | Standard Deviation 11.2 |
| EYLEA | BCVA Change From Baseline (No. of Letters) by Visit | Change from baseline at Week 52 | 7.2 letters | Standard Deviation 13.2 |
| EYLEA | BCVA Change From Baseline (No. of Letters) by Visit | Change from baseline at Week 28 | 6.6 letters | Standard Deviation 12.4 |
Secondary
BCVA Change From Baseline (No. of Letters) to Week 16
BCVA (with spectacles or other visual corrective devices) using ETDRS testing was reported in letters read correctly. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. One eye (study eye) contributed to the analysis.
Time frame: Baseline (Day 0), Week 16
Population: This analysis population includes all subjects who were randomized, received at least 1 treatment, had a baseline value, and had at least 1 postbaseline measurement of the primary efficacy variable, BCVA. Subjects were analyzed according to the actual treatment received with LOCF imputation of missing values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ESBA1008 | BCVA Change From Baseline (No. of Letters) to Week 16 | Baseline (Day 0) | 54.1 letters | Standard Deviation 13.9 |
| ESBA1008 | BCVA Change From Baseline (No. of Letters) to Week 16 | Change from baseline | 6.0 letters | Standard Deviation 13.3 |
| EYLEA | BCVA Change From Baseline (No. of Letters) to Week 16 | Baseline (Day 0) | 55.6 letters | Standard Deviation 12.3 |
| EYLEA | BCVA Change From Baseline (No. of Letters) to Week 16 | Change from baseline | 6.6 letters | Standard Deviation 9.2 |
Comparison: An analysis of variance (ANOVA) model with treatment and baseline BCVA categories (\< 55 and ≥ 55 letters) as class variables was used to estimate the treatment group differences (ESBA1008 - EYLEA) in the primary efficacy endpoint, BCVA Change from baseline to Week 16.80% CI: [-3.72, 2.56]
Secondary
Central Subfield Thickness (CSFT) Change From Baseline by Visit
CSFT (average thickness in the central subfield centered at the fovea) as measured using Spectral-Domain Optical Coherence Tomography (SD-OCT). Reduction in CSFT measurement from baseline indicates improvement. One eye (study eye) contributed to the analysis.
Time frame: Baseline (Day 0), Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56
Population: This analysis population includes all subjects who were randomized, received at least 1 treatment, had a baseline value, and had at least 1 postbaseline measurement of the primary efficacy variable, BCVA. Subjects were analyzed according to the actual treatment received with LOCF imputation of missing values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ESBA1008 | Central Subfield Thickness (CSFT) Change From Baseline by Visit | Change from baseline at Week 16 | -188.4 microns | Standard Deviation 121 |
| ESBA1008 | Central Subfield Thickness (CSFT) Change From Baseline by Visit | Change from baseline at Week 32 | -205.8 microns | Standard Deviation 124.3 |
| ESBA1008 | Central Subfield Thickness (CSFT) Change From Baseline by Visit | Change from baseline at Week 4 | -184.7 microns | Standard Deviation 118.9 |
| ESBA1008 | Central Subfield Thickness (CSFT) Change From Baseline by Visit | Change from baseline at Week 36 | -213.0 microns | Standard Deviation 132.4 |
| ESBA1008 | Central Subfield Thickness (CSFT) Change From Baseline by Visit | Change from baseline at Week 20 | -207.0 microns | Standard Deviation 123.2 |
| ESBA1008 | Central Subfield Thickness (CSFT) Change From Baseline by Visit | Change from baseline at Week 40 | -200.6 microns | Standard Deviation 143.6 |
| ESBA1008 | Central Subfield Thickness (CSFT) Change From Baseline by Visit | Change from baseline at Week 12 | -199.5 microns | Standard Deviation 126.7 |
| ESBA1008 | Central Subfield Thickness (CSFT) Change From Baseline by Visit | Change from baseline at Week 44 | -196.1 microns | Standard Deviation 120.2 |
| ESBA1008 | Central Subfield Thickness (CSFT) Change From Baseline by Visit | Change from baseline at Week 24 | -194.0 microns | Standard Deviation 127.9 |
| ESBA1008 | Central Subfield Thickness (CSFT) Change From Baseline by Visit | Change from baseline at Week 48 | -213.0 microns | Standard Deviation 129.7 |
| ESBA1008 | Central Subfield Thickness (CSFT) Change From Baseline by Visit | Change from baseline at Week 8 | -198.5 microns | Standard Deviation 117.6 |
| ESBA1008 | Central Subfield Thickness (CSFT) Change From Baseline by Visit | Change from baseline at Week 52 | -210.5 microns | Standard Deviation 130.6 |
| ESBA1008 | Central Subfield Thickness (CSFT) Change From Baseline by Visit | Change from baseline at Week 28 | -210.0 microns | Standard Deviation 125 |
| ESBA1008 | Central Subfield Thickness (CSFT) Change From Baseline by Visit | Change from baseline at Week 56 | -196.8 microns | Standard Deviation 135.4 |
| ESBA1008 | Central Subfield Thickness (CSFT) Change From Baseline by Visit | Baseline (Day 0) | 490.1 microns | Standard Deviation 149.2 |
| EYLEA | Central Subfield Thickness (CSFT) Change From Baseline by Visit | Change from baseline at Week 56 | -180.4 microns | Standard Deviation 121.6 |
| EYLEA | Central Subfield Thickness (CSFT) Change From Baseline by Visit | Baseline (Day 0) | 495.7 microns | Standard Deviation 144.6 |
| EYLEA | Central Subfield Thickness (CSFT) Change From Baseline by Visit | Change from baseline at Week 4 | -153.0 microns | Standard Deviation 95.1 |
| EYLEA | Central Subfield Thickness (CSFT) Change From Baseline by Visit | Change from baseline at Week 8 | -176.1 microns | Standard Deviation 106.5 |
| EYLEA | Central Subfield Thickness (CSFT) Change From Baseline by Visit | Change from baseline at Week 12 | -186.2 microns | Standard Deviation 113.6 |
| EYLEA | Central Subfield Thickness (CSFT) Change From Baseline by Visit | Change from baseline at Week 16 | -163.2 microns | Standard Deviation 116.4 |
| EYLEA | Central Subfield Thickness (CSFT) Change From Baseline by Visit | Change from baseline at Week 20 | -184.8 microns | Standard Deviation 118.5 |
| EYLEA | Central Subfield Thickness (CSFT) Change From Baseline by Visit | Change from baseline at Week 24 | -164.0 microns | Standard Deviation 121.8 |
| EYLEA | Central Subfield Thickness (CSFT) Change From Baseline by Visit | Change from baseline at Week 28 | -185.9 microns | Standard Deviation 117.9 |
| EYLEA | Central Subfield Thickness (CSFT) Change From Baseline by Visit | Change from baseline at Week 32 | -166.4 microns | Standard Deviation 123.2 |
| EYLEA | Central Subfield Thickness (CSFT) Change From Baseline by Visit | Change from baseline at Week 36 | -185.3 microns | Standard Deviation 117.7 |
| EYLEA | Central Subfield Thickness (CSFT) Change From Baseline by Visit | Change from baseline at Week 40 | -175.2 microns | Standard Deviation 124.1 |
| EYLEA | Central Subfield Thickness (CSFT) Change From Baseline by Visit | Change from baseline at Week 44 | -184.6 microns | Standard Deviation 121.7 |
| EYLEA | Central Subfield Thickness (CSFT) Change From Baseline by Visit | Change from baseline at Week 48 | -175.7 microns | Standard Deviation 124.3 |
| EYLEA | Central Subfield Thickness (CSFT) Change From Baseline by Visit | Change from baseline at Week 52 | -198.8 microns | Standard Deviation 123.4 |
Secondary
One-Month BCVA Changes (No. of Letters) Following No Treatment for 1-Month
The purpose of this outcome measure was to assess the stability of BCVA during the second month of 8-week/12-week treatment cycles and specifically to identify potential under treatment. BCVA (with spectacles or other visual corrective devices) using ETDRS testing was reported in letters read correctly. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. One eye (study eye) contributed to the analysis.
Time frame: Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56
Population: This analysis population includes all subjects who were randomized, received at least 1 treatment, had a baseline value, and had at least 1 postbaseline measurement of the primary efficacy variable, BCVA. Subjects were analyzed according to the actual treatment received with LOCF imputation of missing values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ESBA1008 | One-Month BCVA Changes (No. of Letters) Following No Treatment for 1-Month | Change from Week 28 to Week 32 | -1.7 letters | Standard Deviation 4.6 |
| ESBA1008 | One-Month BCVA Changes (No. of Letters) Following No Treatment for 1-Month | Change from Week 44 to Week 48 | NA letters | — |
| ESBA1008 | One-Month BCVA Changes (No. of Letters) Following No Treatment for 1-Month | Change from Week 20 to Week 24 | -0.4 letters | Standard Deviation 4.8 |
| ESBA1008 | One-Month BCVA Changes (No. of Letters) Following No Treatment for 1-Month | Change from Week 48 to Week 52 | -0.1 letters | Standard Deviation 4.3 |
| ESBA1008 | One-Month BCVA Changes (No. of Letters) Following No Treatment for 1-Month | Change from Week 36 to Week 40 | 0.1 letters | Standard Deviation 7.3 |
| ESBA1008 | One-Month BCVA Changes (No. of Letters) Following No Treatment for 1-Month | Change from Week 52 to Week 56 | NA letters | — |
| ESBA1008 | One-Month BCVA Changes (No. of Letters) Following No Treatment for 1-Month | Change from Week 12 to Week 16 | 0.3 letters | Standard Deviation 5.7 |
| EYLEA | One-Month BCVA Changes (No. of Letters) Following No Treatment for 1-Month | Change from Week 52 to Week 56 | 0.0 letters | Standard Deviation 4.2 |
| EYLEA | One-Month BCVA Changes (No. of Letters) Following No Treatment for 1-Month | Change from Week 12 to Week 16 | -0.2 letters | Standard Deviation 5.1 |
| EYLEA | One-Month BCVA Changes (No. of Letters) Following No Treatment for 1-Month | Change from Week 20 to Week 24 | 0.9 letters | Standard Deviation 5.5 |
| EYLEA | One-Month BCVA Changes (No. of Letters) Following No Treatment for 1-Month | Change from Week 28 to Week 32 | -0.1 letters | Standard Deviation 3.6 |
| EYLEA | One-Month BCVA Changes (No. of Letters) Following No Treatment for 1-Month | Change from Week 36 to Week 40 | -0.7 letters | Standard Deviation 4 |
| EYLEA | One-Month BCVA Changes (No. of Letters) Following No Treatment for 1-Month | Change from Week 44 to Week 48 | 0.2 letters | Standard Deviation 4.2 |
| EYLEA | One-Month BCVA Changes (No. of Letters) Following No Treatment for 1-Month | Change from Week 48 to Week 52 | NA letters | — |
Secondary
One-Month BCVA Changes (No. of Letters) Following Treatment by Visit
The purpose of this outcome measure was to assess the potential treatment needs present at these treatment visits. BCVA (with spectacles or other visual corrective devices) using ETDRS testing was reported in letters read correctly. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. One eye (study eye) contributed to the analysis.
Time frame: Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52
Population: This analysis population includes all subjects who were randomized, received at least 1 treatment, had a baseline value, and had at least 1 postbaseline measurement of the primary efficacy variable, BCVA. Subjects were analyzed according to the actual treatment received with LOCF imputation of missing values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ESBA1008 | One-Month BCVA Changes (No. of Letters) Following Treatment by Visit | Change from Week 16 to Week 20 | 1.5 letters | Standard Deviation 5.7 |
| ESBA1008 | One-Month BCVA Changes (No. of Letters) Following Treatment by Visit | Change from Week 24 to Week 28 | 1.2 letters | Standard Deviation 5.6 |
| ESBA1008 | One-Month BCVA Changes (No. of Letters) Following Treatment by Visit | Change from Week 32 at Week 36 | -0.5 letters | Standard Deviation 7.9 |
| ESBA1008 | One-Month BCVA Changes (No. of Letters) Following Treatment by Visit | Change from Week 40 to Week 44 | NA letters | — |
| ESBA1008 | One-Month BCVA Changes (No. of Letters) Following Treatment by Visit | Change from Week 44 to Week 48 | -0.8 letters | Standard Deviation 4.2 |
| ESBA1008 | One-Month BCVA Changes (No. of Letters) Following Treatment by Visit | Change from Week 48 to Week 52 | NA letters | — |
| EYLEA | One-Month BCVA Changes (No. of Letters) Following Treatment by Visit | Change from Week 44 to Week 48 | NA letters | — |
| EYLEA | One-Month BCVA Changes (No. of Letters) Following Treatment by Visit | Change from Week 16 to Week 20 | 0.6 letters | Standard Deviation 5.1 |
| EYLEA | One-Month BCVA Changes (No. of Letters) Following Treatment by Visit | Change from Week 40 to Week 44 | 0.8 letters | Standard Deviation 5.2 |
| EYLEA | One-Month BCVA Changes (No. of Letters) Following Treatment by Visit | Change from Week 24 to Week 28 | -1.6 letters | Standard Deviation 7.7 |
| EYLEA | One-Month BCVA Changes (No. of Letters) Following Treatment by Visit | Change from Week 48 to Week 52 | 0.5 letters | Standard Deviation 3.6 |
| EYLEA | One-Month BCVA Changes (No. of Letters) Following Treatment by Visit | Change from Week 32 at Week 36 | -0.2 letters | Standard Deviation 5.1 |
Secondary
Two-Months BCVA Changes (No. of Letters) Following No Treatment for 1 Month in ESBA Treatment Group
BCVA (with spectacles or other visual corrective devices) using ETDRS testing was reported in letters read correctly. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. This outcome measure was pre-specified for ESBA1008 arm only. One eye (study eye) contributed to the analysis.
Time frame: Week 36, Week 44, Week 48, Week 56
Population: This analysis population includes all subjects who were randomized, received at least 1 treatment, had a baseline value, and had at least 1 postbaseline measurement of the primary efficacy variable, BCVA. Subjects were analyzed according to the actual treatment received with LOCF imputation of missing values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ESBA1008 | Two-Months BCVA Changes (No. of Letters) Following No Treatment for 1 Month in ESBA Treatment Group | Change from Week 36 to Week 44 | 0.8 letters | Standard Deviation 7.1 |
| ESBA1008 | Two-Months BCVA Changes (No. of Letters) Following No Treatment for 1 Month in ESBA Treatment Group | Change from Week 48 to Week 56 | -1.3 letters | Standard Deviation 5 |