Study of Efficacy and Safety of Brolucizumab Versus Panretinal Photocoagulation Laser in Patients With Proliferative Diabetic Retinopathy

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 compared to panretinal photocoagulation laser (PRP) in patients with proliferative diabetic retinopathy (PDR). This evaluation will provide information that brolucizumab is non-inferior to PRP with respect to the change in best corrected visual acuity at Week 54.

Official Title
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A 96-week, Two-arm, Randomized, Single-masked, Multi-center, Phase III Study Assessing the Efficacy and Safety of Brolucizumab 6 mg Compared to Panretinal Photocoagulation Laser in Patients With Proliferative Diabetic Retinopathy

Conditions
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Proliferative Diabetic Retinopathy

Intervention / Treatment
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* Biological: Brolucizumab 6 mg
* Procedure: Panretinal photocoagulation laser


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent must be obtained prior to participation Able to complete adequate fundus photographs and retinal images Diagnosis of type 1 or 2 Diabetes Mellitus (DM) and HbA1c less than or equal to 12% at screening DM treatment stable for at least 3 months PDR diagnosis with no previous PRP treatment in the study eye Exclusion Criteria: Concomitant conditions or ocular disorders in the study eye at Screening or Baseline that could compromise a response to study treatment. Presence of diabetic macular edema in the study eye Active infection or inflammation in the study eye Uncontrolled glaucoma (IOP greater than 25 mmHg) Intravitreal anti-VEGF treatment within 6 months Treatment with intraocular corticosteroids End stage renal disease requiring dialysis or kidney transplant Uncontrolled blood pressure Systemic anti-VEGF therapy at any time 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brolucizumab Arm<br>Intra-vitreal injection | Biological: Brolucizumab 6 mg<br>* 3 x q6w loading injections, followed by q12w maintenance through Week 90<br>* Other names: RTH258;|
| Active Comparator: Panretinal photocoagulation laser Arm<br>laser | Procedure: Panretinal photocoagulation laser<br>* initial treatment in 1-4 sessions up to Week 12, followed with additional PRP treatment as needed<br>* Other names: PRP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in BCVA | To demonstrate that brolucizumab is non-inferior to PRP with respect to the change from Baseline in visual acuity at Week 54 | At Week 54 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with no PDR at Week 54 | To demonstrate that brolucizumab is superior to PRP in reducing diabetic retinopathy severity at Week 54 | At Week 54 | 
| Proportion of subjects with center-involved DME up to Week 54 | To demonstrate that brolucizumab is superior to PRP in preventing the development of center-involved DME up to Week 54 | At Week 54 | 
| Area under the curve in change from Baseline in BCVA up to Week 54 and Week 96 | To compare the effect of brolucizumab relative to PRP with respect to visual acuity | From Baseline in BCVA up to Week 54 and Week 96 | 
| Change from Baseline in ETDRS Diabetic Retinopathy Severity Scale (DRSS) score at Week 54 and Week 96 | To compare the effect of brolucizumab relative to PRP on diabetic retinopathy status | From Baseline score to Week 54 and Week 96 | 
| Proportion of subjects with no PDR at Week 96 | To compare the effect of brolucizumab relative to PRP on diabetic retinopathy status | At Week 96 | 
| Proportion of study eyes developing vision-threatening complications associated with diabetic retinopathy up to Week 54 and Week 96 | To compare the effect of brolucizumab relative to PRP on ocular complications | At Week 54 and Week 96 | 
| Proportion of subjects with center-involved DME up to Week 96 | To compare the effect of brolucizumab relative to PRP on ocular complications | At Week 96 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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proliferative diabetic retinophathy, retinal neovascularization, anti-VEGF, brolucizumab, intravitreal injection, panretinal photocoagulation