Efficacy and Safety Study of ESBA1008 Versus EYLEA®

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Prospective, Randomized, Double-Masked, Multicenter, Two Arm Study Comparing the Efficacy and Safety of ESBA1008 Versus EYLEA® in Subjects With Exudative Age-Related Macular Degeneration

Conditions
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Exudative Age-Related Macular Degeneration

Intervention / Treatment
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* Drug: ESBA1008 solution
* Drug: Aflibercept


Participation Criteria
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Eligibility Criteria
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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 exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ESBA1008<br>ESBA1008 solution, 7 intravitreal (IVT) injections, as specified in protocol | Drug: ESBA1008 solution<br>* For intravitreal (IVT) injection<br>|
| Active Comparator: EYLEA<br>Aflibercept, 8 intravitreal (IVT) injections, as specified in protocol | Drug: Aflibercept<br>* For intravitreal (IVT) injection<br>* Other names: EYLEA®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline (Day 0), Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline (Day 0), Week 16 | 
| 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. | 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 | 
| 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. | 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 | 
| 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. | Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56 | 
| 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. | Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56 | 
| 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. | Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52 | 
| 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. | Week 36, Week 44, Week 48, Week 56 | 
| 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. | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AMD, Intravitreal injection, Retina, Age-Related Macular Degeneration, Wet, Exudative