Efficacy and Safety Study of ESBA1008 Versus EYLEA®

Phase 2

Completed

• Conditions: Exudative Age-Related Macular Degeneration
• Interventions: Drug: ESBA1008 solution; Drug: Aflibercept

• Registration Number: NCT01796964
• Lead Sponsor: Alcon Research

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.

Study Timeline

• Study First Submitted: 2013-02-20
• Study First Submitted QC: 2013-02-20
• Study First Posted: 2013-02-22
• Study Start: 2013-03
• Primary Completion: 2013-10
• Study Completion: 2014-08
• Disposition First Submitted: 2014-09-09
• Disposition First Submitted QC: 2014-09-09
• Disposition First Posted: 2014-09-18
• Status Verified: 2016-01
• Results First Submitted: 2016-01-11
• Results First Submitted QC: 2016-01-11
• Last Update Submitted: 2016-01-11
• Results First Posted: 2016-02-09
• Last Update Posted: 2016-02-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 173

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ESBA1008	ESBA1008 solution	ESBA1008 solution, 7 intravitreal (IVT) injections, as specified in protocol
EYLEA	Aflibercept	Aflibercept, 8 intravitreal (IVT) injections, as specified in protocol

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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.
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.