To Compare Brolucizumab to Aflibercept in Chinese Patients With Visual Impairment Due to Diabetic Macular Edema

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of brolucizumab in treatment of Chinese patients with visual impairment due to Diabetic Macular Edema.

Official Title
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A One-Year, Randomized, Double-Masked, Multicenter, Phase III, Two-Arm Study Assessing the Efficacy and Safety of Brolucizumab Versus Aflibercept in Adult Chinese Patients With Visual Impairment Due to Diabetic Macular Edema

Conditions
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Diabetic Macular Edema

Intervention / Treatment
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* Drug: Brolucizumab
* Drug: Aflibercept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with type 1 or type 2 diabetes mellitus Visual impairment due to Diabetic Macular Edema Exclusion Criteria: Any active intraocular or periocular infection or active intraocular inflammation Structural damage of the fovea Uncontrolled glaucoma Neovascularization of the iris Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brolucizumab 6 mg<br>5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance | Drug: Brolucizumab<br>* 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance<br>* Other names: RTH258;|
| Active Comparator: Aflibercept 2 mg<br>5 x every 4 weeks loading then every 8 weeks maintenance | Drug: Aflibercept<br>* 5 x every 4 weeks loading then every 8 weeks maintenance<br>* Other names: Eylea;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in best-corrected visual acuity (BCVA) | To demonstrate that brolucizumab is non-inferior to aflibercept with respect to the visual outcome | Baseline to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average change in BCVA | To demonstrate that brolucizumab is non-inferior to aflibercept with respect to the visual outcome | Baseline, over period Week 40 to Week 52 | 
| Proportion of patients maintained treatment regimen of every 12 weeks in brolucizumab arm | To estimate the proportion of patients treated at every 12 weeks (q12w) frequency with brolucizumab | Baseline up to Week 52 | 
| Proportion of patients maintained dosing regimen of every 12 weeks (q12w) interval up to Week 52, within those patients that qualified for q12w at dosing regimen at Week 36 | To estimate the predictive value of the first q12w cycle for maintenance of q12w treatment with brolucizumab | Up to Week 52 | 
| Change in BCVA | To evaluate the efficacy of brolucizumab relative to aflibercept over the time period | Baseline up to Week 52 | 
| Average change in BCVA | To evaluate the efficacy of brolucizumab relative to aflibercept over the time period | Baseline up to Week 52, over period Week 20 to Week 52, Period Week 28 to Week 52 | 
| Proportion of patients who gain in BCVA of ≥5, ≥10 and ≥15 ETDRS letters from baseline to each post-baseline visit | To evaluate the efficacy of brolucizumab relative to aflibercept over the time period | Baseline up to Week 52 | 
| Time to achieve gain of ≥5, ≥10 and ≥15 ETDRS letters from baseline (or reaching a score of 84 or more) | To evaluate the efficacy of brolucizumab relative to aflibercept over the time period | Baseline up to Week 52 | 
| Proportion of patients who loss in BCVA of ≥5, ≥10 and ≥15 ETDRS letters from baseline to each post-baseline visit | To evaluate the efficacy of brolucizumab relative to aflibercept over the time period | Baseline up to Week 52 | 
| Proportion of patients who have absolute BCVA ≥73 ETDRS letters at each post-baseline visit | To evaluate the efficacy of brolucizumab relative to aflibercept over the time period | Baseline up to Week 52 | 
| Proportion of patients need q8w treatment | To evaluate the efficacy related to dosing regimen of brolucizumab | Week 32 | 
| Proportion of patients with per planned dosing regimen (q8w or q12w) | To evaluate the efficacy related to dosing regimen | Week 52 | 
| Change in Central Subfield Thickness (CSFT) at each assessment visit | To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters | Baseline up to Week 52 | 
| Average change in CSFT | To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters | Baseline, over period of Week 4 to Week 52, over period of Week 40 to Week 52 | 
| Proportion of patient who have normal CSFT (<280 microns) at each assessment visit | To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters | Baseline up to Week 52 | 
| Change in Central Subfield Thickness-neurosensory retina (CSFTns) at each assessment visit | To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters | Baseline up to Week 52 | 
| Average change in CSFTns | To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters | Baseline, over the period of Week 4 to Week 52, over period of Week 40 to Week 52 | 
| Proportion of patients with presence of subretinal fluid (SRF), Intraretinal fluid (IRF) and simultaneous absence of SRF and IRF at each assessment visit | To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters | Baseline up to Week 52 | 
| Proportion of patients with presence of leakage on fluorescein angiography (FA) | To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters | Week 52 | 
| Change from baseline in ETDRS Diabetic Retinopathy Severity Scale score at each assessment visit | To evaluate the efficacy of brolucizumab relative to aflibercept on the Diabetic Retinopathy status | Baseline up to Week 52 | 
| Number of patients with progression to proliferative diabetic retinopathy (PDR) as assessed by ETDRS-DRSS Score of at least 61 by Week 52 | To evaluate the efficacy of brolucizumab relative to aflibercept on the Diabetic Retinopathy status | Week 52 | 
| Change in patient reported outcomes (Visual Function Questionnaire-25) total and subscale scores | To assess visual function-related patient reported outcomes (VFQ-25) following treatment with brolucizumab relative to aflibercept. The VFQ-25 includes a series of 25 questions pertaining to vision or feelings about a vision condition. Answers are selected among a numbered list of possible responses, the values of which are ultimately recoded and converted to a 0 to 100 scale. Items within each subscale are averaged together to create 12 subscale scores. An overall composite score will be calculated by averaging vision-targeted subscale scores, excluding the general health rating question. | Baseline up to Week 28 and Week 52 | 
| Systemic brolucizumab concentration | To confirm the systemic brolucizumab exposure in a subset of patients. | Approximately 24 hours post Day 1 treatment and approximately 24 hours post Week 24 treatment | 
| Proportion of patients who have positive anti-drug antibody status in brolucizumab arm | To assess the immunogenicity of brolucizumab | At Screening, Week 4, 12, 24, 36, and 52 (End of Study) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetic Macular Edema, Intravitreal injection, brolucizumab, aflibercept