An Extension Study Assessing the Efficacy and Safety of Brolucizumab in a Treat-to-Control Regimen in Patients With Neovascular Age-related Macular Degeneration Who Have Completed the CRTH258A2303 (TALON) Study

Study Overview
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Brief Summary
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The purpose of this extension study is to evaluate the efficacy and safety of brolucizumab used in a Treat-to-Control-regimen for treatment of patients with neovascular age-related macular degeneration who have completed the CRTH258A2303 (TALON) study. The main objective is to assess brolucizumab's potential for long durability up to 20 weeks. All eligible participants will be treated with brolucizumab regardless of their treatment in the TALON study. The study period is 56 weeks including post-treatment follow-up.

Detailed Description
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This study is a 56-week, open-label, one-arm extension study in participants who have completed the CRTH258A2303 study (TALON). Participants who consent and meet all the inclusion and none of the exclusion criteria will be enrolled into this extension study and receive brolucizumab 6 mg in a TtC regimen, irrespective of the treatment received in the core study. It is estimated that 622 participants from the core study will enter the extension study (10% dropout rate expected). The maximum study duration for one participant is 56 weeks, including post-treatment follow-up. There will be two periods in this study: Treat-to-Control treatment period: from Baseline (Day 1) to Week 52 Post-treatment follow-up period: from Week 52 to Week 56. All participants will be treated with brolucizumab regardless of their treatment in the TALON study (brolucizumab or aflibercept). Treatment intervals can then be extended by 4 weeks at a time based on the investigator's judgment of visual and/or anatomic outcomes. The treatment intervals should be by 4 weeks at a time if disease activity recurs.

Official Title
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A 56-week Phase IIIb/IV, Open-label, One-arm Extension Study to Assess the Efficacy and Safety of Brolucizumab 6 mg in a Treat-to-Control Regimen With Maximum Treatment Intervals up to 20 Weeks for the Treatment of Patients With Neovascular Age-related Macular Degeneration Who Have Completed the CRTH258A2303 (TALON) Study

Conditions
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Neovascular Age-related Macular Degeneration

Intervention / Treatment
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* Drug: brolucizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Successfully completed TALON core study at week 64 (End of Study) Exclusion Criteria: Medical condition or personal circumstance which precludes study participation or compliance with study procedures, as assessed by the Investigator Discontinued study treatment in the core study Anti-VEGF treatment is futile in the study eye, in the Investigator's opinion. Pregnant or nursing (lactating) women Women of child-bearing potential not using highly effective methods of contraception

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: brolucizumab 6 mg<br>Participants will receive brolucizumab 6 mg/0.05 mL solution by intravitreal injection in a Treat-to-Control regimen with injection intervals from 4 up to 20 weeks. Intervals may be changed in steps of 4 weeks at a time per investigators' decisions determined by the disease activity. | Drug: brolucizumab<br>* brolucizumab 6 mg/0.05 mL solution for intravitreal injection<br>* Other names: RTH258;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extended durability of brolucizumab in a Treat-to-Control regimen | Duration of the last interval with no disease activity up to week 56 | 56 weeks | 
| Functional outcomes of brolucizumab in a Treat-to-Control regimen | Change in BCVA from baseline at Week 52 and Week 56 | Baseline, 52 and 56 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anatomical outcome of brolucizumab in all patients - as measured by the change in central subfield thickness | Change in central subfield thickness from baseline to Week 52 and Week 56 | Baseline, 52 and 56 weeks | 
| Anatomical outcome of brolucizumab in all patients - as assessed by spectral domain ocular coherence tomography | Number of visits with presence of intraretinal fluid and/or subretinal fluid, and sub-retinal pigment epithelium fluid in the central subfield, as assessed by spectral domain ocular coherence tomography at week 52 and week 56 | Baseline, 52 and 56 weeks | 
| Durability of brolucizumab in all patients - as measured by duration of the last interval with no disease activity | Duration of the last interval with no disease activity up to week 56 | Baseline and week 56 | 
| Durability of brolucizumab in all patients - as measured by duration of the maximal intervals with no disease activity | Duration of the maximal intervals with no disease activity up to week 56 | Baseline and week 56 | 
| Durability of brolucizumab in all patients - as measured by change of the duration of last interval with no disease activity | Change of the duration of last interval with no disease activity between baseline and week 56 | Baseline and week 56 | 
| Functional outcomes of brolucizumab per randomized arm in the core study | Change in Best Corrected Visual Acuity (BCVA) from baseline to week 52 and week 56 | Baseline, 52 and 56 weeks | 
| Safety of brolucizumab - as measured by the indicence of ocular and non ocular Adverse Events (AEs) | Occurrence of Ocular and Non-ocular AEs up to Week 56 | up to Week 56 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neovascular age-related macular degeneration, wet age-related macular degeneration, wet AMD, choroidal neovascularization, individualized treatment, anti-VEGF