Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
Change in Best-Corrected Visual Acuity |
To demonstrate that brolucizumab 6 mg is not inferior to aflibercept 2 mg with respect to the change in BCVA |
Baseline to Week 48 |
|
| Secondary |
Average change in Best-Corrected Visual Acuity |
To demonstrate that brolucizumab 6 mg is not inferior to aflibercept 2 mg with respect to the change in BCVA |
Baseline, over the period Week 36 to Week 48 |
|
| Secondary |
Proportion of subjects with treatment regimen of every 12 weeks in brolucizumab arm |
To estimate the proportion of q12w subjects (1 injection every 12 weeks) up to Week 48 in the brolucizumab 6 mg treatment arm" |
Baseline up to Week 48 |
|
| Secondary |
Proportion of patients with treatment regimen of every 12 weeks (q12w) interval at Week 48 of those who do not need every 8 weeks treatment interval in brolucizumab arm |
To estimate the predictive value of the first regimen of every 12 weeks (q12w) cycle (at Week 16 and Week 20) for maintenance of q12w treatment regimen |
Week 16, Week 20 and Week 48 |
|
| Secondary |
Change in Best Corrected Visual Acuity (BCVA) |
To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period |
Baseline up to Week 48 |
|
| Secondary |
Average change in Best-Corrected Visual Acuity |
To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period |
Baseline, over the period of Week 4 to Week 48 |
|
| Secondary |
Average change in Best-Corrected Visual Acuity |
To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period |
Baseline, over the period of Week 12 to Week 48 |
|
| Secondary |
Proportion of patients who gain in best-correct visual acuity of 15/10/5 letters or more |
To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period |
Baseline up to Week 48 |
|
| Secondary |
Percentage of subjects with Best-Corrected Visual Acuity of 73 letters or more at each visit |
To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period |
Baseline up to Week 48 |
|
| Secondary |
Proportion of subjects who loss in best-corrected visual acuity of 15/10/5 letters or more |
To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period |
Baseline up to Week 48 |
|
| Secondary |
Change in Central Subfield Thickness Total |
To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters |
Baseline up to Week 48 |
|
| Secondary |
Average change in Central Subfield Thickness Total |
To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters |
Baseline, over the period of Week 36 to Week 48 |
|
| Secondary |
Average Change in Central Subfield Thickness Total |
To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters |
Baseline, over the period of Week 4 to Week 48 |
|
| Secondary |
Change in Central Subfield Thickness-neurosensory retina |
To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters |
From Baseline up to Week 48 |
|
| Secondary |
Change in in area of choroidal neovascularization lesion |
To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters |
Baseline, Weeks 12 and Week 48 |
|
| Secondary |
Proportion of subjects who have presence of subretinal and/or intraretinal fluid (central subfield) |
To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters |
Baseline up to Week 48, specifically at Week 16 and Week 48 |
|
| Secondary |
Number of visits with simultaneous absence of subretinal and intraretinal fluid (central subfield) |
To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters |
Over the period of Week 36 to Week 48 |
|
| Secondary |
Proportion of subjects who have presence of subretinal fluid (central subfield) |
To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters |
Baseline up to Week 48 |
|
| Secondary |
Proportion of subjects who have presence of intraretinal fluid (central subfield) |
To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters |
Baseline up to Week 48 |
|
| Secondary |
Proportion of subjects who presence of sub retinal pigment epithelium fluid (central subfield) |
To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters |
Baseline up to Week 48 |
|
| Secondary |
Change in Central Subfield Thickness Total |
To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg at the end of the matched treatment phase |
Baseline up to week 16 |
|
| Secondary |
Proportion of subjects who presence of subretinal and /or intraretinal fluid (central subfield) |
To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg at the end of the matched treatment phase |
At Week 16 |
|
| Secondary |
Proportion of subjects who need every 8 weeks injection |
To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg at the end of the matched treatment phase |
At Week 16 |
|
| Secondary |
Change in subject reported outcomes (Visual Function Questionnaire-25) total and subscale scores |
To assess visual function-related subject reported outcomes following treatment with brolucizumab 6 mg relative to aflibercept 2 mg. 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 Weeks 24 and Week 48 |
|
| Secondary |
Proportion of subjects who have positive anti-drug antibodies status |
To assess immunogenicity of brolucizumab 6 mg |
At Baseline (enrollment), Weeks 4, 12, 24, 36, and 48 (End of Study) |
|
| Secondary |
Pharmacokinetic parameters: Cmax after first brolucizumab 6 mg dose in a subset of subjects |
PK draw 6 hours post-injection on Day 1, after first brolucizumab 6 mg dose in a subset of subjects to assess Cmax (maximum concentration) of brolucizumab at 6 mg following a single intravitreal injection |
Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29 |
|
| Secondary |
Pharmacokinetic parameters: Tmax after first brolucizumab 6 mg dose in a subset of subjects |
PK draw 6 hours post-injection on Day 1, after first brolucizumab 6 mg dose in a subset of subjects to assess Tmax (time to maximum concenration) of brolucizumab at 6 mg following a single intravitreal injection |
Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29 |
|
| Secondary |
Pharmacokinetic parameters: AUClast after first brolucizumab 6 mg dose in a subset of subjects |
PK draw 6 hours post-injection on Day 1, after first brolucizumab 6 mg dose in a subset of subjects to assess AUClast (Area under the curve up to the last validated measurable plasma concentration) of brolucizumab at 6 mg following a single intravitreal injection |
Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29 |
|
| Secondary |
Pharmacokinetic parameters: AUCinf after first brolucizumab 6 mg dose in a subset of subjects |
PK draw 6 hours post-injection on Day 1, after first brolucizumab 6 mg dose in a subset of subjects to assess AUCinf (area under the curve total exposure) of brolucizumab at 6 mg following a single intravitreal injection |
Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29 |
|
| Secondary |
Pharmacokinetic parameters: Thalf after first brolucizumab 6 mg dose in a subset of subjects |
PK draw 6 hours post-injection on Day 1, after first brolucizumab 6 mg dose in a subset of subjects to assess Thalf (time to elimination of half-life) of brolucizumab at 6 mg following a single intravitreal injection |
Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29 |
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