ESBA1008 Microvolume Study

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate a treatment effect of ESBA1008 applied as a microvolume injection or infusion on retinal function and morphology in subjects with exudative age-related macular degeneration (AMD).

Detailed Description
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This 4-cohort study was conducted in 2 stages. Stage 1 consisted out of 2 Cohorts. In each cohort subjects were randomized 10:3 to either receive ESBA1008 (Cohort 1 : 2 injections, Cohort 2 : 1 infusion and 1 injection) or 2 Lucentis injections. Stage 2 was conducted similarly with a different dosing level for ESBA1008 (Cohort 3 and 4). Subjects had follow-up visits at Day 7 and Day 14. All cohorts receiving ESBA1008 on Day 0 also received ESBA1008 6mg/50 μL via injection on Day 28. After the Day 28 visit (all cohorts), subjects returned for follow up visits at Day 42 and Day 56.

Official Title
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A Prospective, Two-Staged, Single-Masked Study to Evaluate the Effect of ESBA1008 Applied by Microvolume Injection or Infusion 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: Ranibizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sign informed consent document; Able to make the required study visits and follow instructions; Age-related macular degeneration in the study eye; Visual acuity within protocol-specified range; 340 μm minimal central subfield thickness (CSFT; Spectralis Equivalent) Other protocol-defined inclusion criteria may apply. Exclusion Criteria: Both eyes: Any active infection or inflammation; Study eye: Any treatment for exudative age-related macular degeneration (AMD) other than vitamin supplements; Study eye: Any current or history of macular or retinal disease; Study eye: Any concurrent intraocular condition such as cataract or diabetic retinopathy that, in the opinion of the Investigator, could either require medical or surgical intervention during the course of the study to prevent or treat visual loss; Study eye: Other ocular conditions or diseases that, in the opinion of the Investigator, could compromise visual acuity; Study Eye: Uncontrolled glaucoma; History of a medical condition that, in the opinion of the Investigator, would preclude scheduled study visits, completion of the study, or a safe administration of investigational product; Women of childbearing potential who are lactating, pregnant, planning to become pregnant, or not using adequate birth control methods for the duration of the study; Intraocular surgery within 3 months of baseline; Study eye: Any history or current evidence of retinal angiomatous proliferation (RAP) lesions based on clinical exam; 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ESBA1008 1.2 mg/10 μL<br>Cohort 1: One intravitreal injection on Day 0, followed by one intravitreal (IVT) injection of ESBA1008 6 mg/50 μL on Day 28 | Drug: ESBA1008 solution<br>* Intravitreal injection or infusion<br>|
| Experimental: ESBA1008 1 mg/8.3 μL<br>Cohort 2: One intravitreal infusion on Day 0, followed by one intravitreal injection of ESBA1008 6 mg/50 μL on Day 28 | Drug: ESBA1008 solution<br>* Intravitreal injection or infusion<br>|
| Experimental: ESBA1008 0.6 mg/10 μL<br>Cohort 3: One intravitreal injection on Day 0, followed by one intravitreal injection of ESBA1008 6 mg/50 μL on Day 28 | Drug: ESBA1008 solution<br>* Intravitreal injection or infusion<br>|
| Experimental: ESBA1008 0.5 mg/8.3 μL<br>Cohort 4: One intravitreal infusion on Day 0, followed by one intravitreal injection of ESBA1008 6 mg/50 μL on Day 28 | Drug: ESBA1008 solution<br>* Intravitreal injection or infusion<br>|
| Active Comparator: Ranibizumab 0.5 mg in 50 μL<br>Cohorts 1-4: One intravitreal injection on Day 0, followed by another intravitreal injection on Day 28 | Drug: Ranibizumab<br>* Intravitreal injection<br>* Other names: LUCENTIS®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Responders Based on CSFT and BCVA Outcomes at Day 14 and Day 28 | A subject was considered a responder if at least 3 out of the following 4 criteria were fulfilled in comparison to baseline: Greater than or equal to 4 letter gain in BCVA at Day 14 Greater than or equal to 4 letter gain in BCVA at Day 28 Greater than or equal to 80 micron decrease in CSFT at Day 14 Greater than or equal to 80 micron decrease in CSFT at Day 28. BCVA was measured by the number of letters read out of a possible 70 letters on the ETDRS chart. One eye (study eye) contributed to the analysis. | Baseline, Day 14, Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in BCVA, Cohort 1 | BCVA (with spectacles or other visual corrective devices) using ETDRS testing was reported in letters read correctly out of 70 letters on the chart. 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 7, Day 14, Day 28, Day 42, Day 56 | 
| Change From Baseline in BCVA, Cohort 2 | BCVA (with spectacles or other visual corrective devices) using ETDRS testing was reported in letters read correctly out of 70 letters on the chart. 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 7, Day 14, Day 28, Day 42, Day 56 | 
| Change From Baseline in BCVA, Cohort 3 | BCVA (with spectacles or other visual corrective devices) using ETDRS testing was reported in letters read correctly out of 70 letters on the chart. 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 7, Day 14, Day 28, Day 42, Day 56 | 
| Change From Baseline in BCVA, Cohort 4 | BCVA (with spectacles or other visual corrective devices) using ETDRS testing was reported in letters read correctly out of 70 letters on the chart. 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 7, Day 14, Day 28, Day 42, Day 56 | 
| Change From Baseline in CSFT, Cohort 1 | CSFT was assessed by Spectral-Domain Optical Coherence Tomography (SD-OCT) and measured in microns. A decrease in CSFT indicates improvement. One eye (study eye) contributed to the analysis. | Baseline, Day 7, Day 14, Day 28, Day 42, Day 56 | 
| Change From Baseline in CSFT, Cohort 2 | CSFT was assessed by SD-OCT and measured in microns. A decrease in CSFT indicates improvement. One eye (study eye) contributed to the analysis. | Baseline, Day 7, Day 14, Day 28, Day 42, Day 56 | 
| Change From Baseline in CSFT, Cohort 3 | CSFT was assessed by SD-OCT and measured in microns. A decrease in CSFT indicates improvement. One eye (study eye) contributed to the analysis. | Baseline, Day 7, Day 14, Day 28, Day 42, Day 56 | 
| Change From Baseline in CSFT, Cohort 4 | CSFT was assessed by SD-OCT and measured in microns. A decrease in CSFT indicates improvement. One eye (study eye) contributed to the analysis. | Baseline, Day 7, Day 14, Day 28, Day 42, Day 56 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Exudative Age-Related Macular Degeneration, Wet AMD, Choroidal neovascularization (CNV), Vascular endothelial growth factor (VEGF)