Study to Assess the Efficacy and Safety of Brolucizumab 6mg Compared to Aflibercept 2 mg in a Treat-to-control Regimen (TALON)

Study Overview
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Brief Summary
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The was a 64-week randomized, double-masked, multi-center, active-controlled, two-arm study in patients with neovascular age related macular degeneration (nAMD) who have not previously received anti- vascular endothelial growth factor (VEGF) treatment.

Detailed Description
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The was a 64-week randomized, double-masked, multi-center, active-controlled, two-arm study in patients with neovascular age related macular degeneration (nAMD) who have not previously received anti- vascular endothelial growth factor (VEGF) treatment. At the baseline Visit, subjects who met the eligibility criteria were randomized in a 1:1 ratio to receive either: -Brolucizumab 6 mg: 3 × 4-week injections and one 8-week injection, followed by Treat-to- Control treatment from Week 16 up to Week 60/62 -Aflibercept 2 mg: 3 × 4-week injections and one 8-week injection, followed by Treat-to-Control treatment from Week 16 up to Week 60/62. For all subjects, the last potential study treatment was at the Week 60 visit (or at the Week 62 visit for subjects whose actual treatment interval would require a treatment at Week 62). The initiation phase starts on Day 1 and ends on Week 16. Treat to Control regimen starts on Week 16 until end of treatment (Week 60/62). In both treatment arms, treatment intervals after the initiation phase were either 8 weeks, 12 weeks, or 16 weeks. Per the original protocol, if it was determined that a patient required more frequent injections than q8w, he/she would be moved to a q4w treatment interval. However, this option was removed per Protocol amendment 02, after which, dosing intervals shorter than q8w were not permitted. At the investigator's discretion, an inspection visit 6 weeks after the last injection could be performed when the injection interval was extended from 4 weeks to 8 weeks, i.e., after the 3rd injection at Week 8. If there was no disease activity in the study eye at the inspection visit, as assessed by the masked investigator, no treatment should be administered and the next visit and injection should take place 2 weeks later, i.e., 8 weeks after the previous study treatment. If disease activity was observed by the masked investigator in the study eye at the inspection visit at Week 14, the study treatment should be administered by the unmasked investigator, and the subject should be discontinued from further study treatment at the next visit. Inspection visits 10 weeks and 14 weeks after the last injection could have been performed when the injection interval was extended from 8 weeks to 12 weeks, and from 12 weeks to 16 weeks, respectively.

Official Title
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A 64-week, Two-arm, Randomized, Double-masked, Multicenter, Phase IIIb Study Assessing the Efficacy and Safety of Brolucizumab 6 mg Compared to Aflibercept 2 mg in a Treat-to-control Regimen in Patients With Neovascular Agerelated Macular Degeneration (TALON)

Conditions
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Age-related Macular Degeneration

Intervention / Treatment
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* Biological: Brolucizumab 6 mg
* Biological: Aflibercept 2 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent must be obtained prior to participation in the study Male or female patients ≥ 50 years of age at screening who are treatment naive Active choroidal neovascularization (CNV) secondary to AMD that affects the central subfield, including retinal angiomatous proliferation (RAP) with a CNV component, confirmed by presence of active leakage from CNV seen by fluorescein angiography and sequellae of CNV, e.g. pigment epithelial detachment (PED), subretinal or sub-retinal pigment epithelium (sub-RPE) hemorrhage, blocked fluorescence, macular edema (study eye) Presence of intraretinal fluid (IRF) or subretinal fluid (SRF) that affects the central subfield, as seen by Spectral Domain Optical Coherence Tomography (SD-OCT) (study eye) Best-corrected visual acuity (BCVA) score between 83 and 38 letters, inclusive, using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at both screening and baseline visit (study eye) Exclusion Criteria: Ocular conditions/disorders at screening or baseline which could, in the opinion of the investigator, prevent response to study treatment or may confound interpretation of study results, compromise visual acuity or require planned medical or surgical intervention during the first 12-month study period, structural damage of the fovea, atrophy or fibrosis at the center of the fovea (study eye) Any active intraocular or periocular infection or active intraocular inflammation, at screening or baseline (study eye) Uncontrolled glaucoma defined as intraocular pressure (IOP) > 25 mmHg on medication, or according to investigator's judgment, at screening or baseline (study eye) Ocular treatments: previous treatment with any anti-vascular endothelial growth factor (VEGF) drugs or investigational drugs, intraocular or periocular steroids, macular laser photocoagulation, photodynamic therapy, vitreoretinal surgery, intraocular surgery (study eye) Stroke or myocardial infarction during the 6-month period prior to baseline Systemic anti-VEGF therapy at any time.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double arm, multi-center
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brolucizumab<br>Intra-vitreal injection | Biological: Brolucizumab 6 mg<br>* 3 x 4-week injections and one 8-week Intra-vitreal injection, followed by Treat-to- Control treatment from Week 16 up to Week 60/62.<br>* Other names: RTH258;|
| Active Comparator: Aflibercept<br>Intra-vitreal injection | Biological: Aflibercept 2 mg<br>* 3 x 4-week injections and one 8-week Intra-vitreal injection, followed by Treat-to- Control treatment from Week 16 up to Week 60/62<br>* Other names: EYLEA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average change in Best-corrected visual acuity | Visual acuity test | At Weeks 28 and 32 | 
| Distribution of the last interval with no disease activity | Treatment interval distribution | Up to Week 32 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distribution of the last interval with no disease activity | Treatment interval distribution | Up to Week 64 | 
| Distribution of the maximal intervals with no disease activity | Treatment interval distribution | Up to Week 64 | 
| Proportion of patients with no disease activit | Disease activity assessment | At Weeks 14 and 16 | 
| Time from the last loading injection to the first visit with no disease activity | Disease activity assessment | Week 8 to week 62 | 
| Average change in Best-corrected visual acuity | Visual acuity test | At Weeks 60 and 64 | 
| Occurrence of Best-corrected visual acuity improvements of ≥ 10 and ≥ 15 letters | Visual acuity test | At Week 32, Week 64, and at the last injection visit | 
| Occurrence of Best-corrected visual acuity ≥ 69 letters | Visual acuity test | At Week 32, at Week 64, and at the last injection visit | 
| Average change from baseline in Central Subfield Thickness | Spectral Domain Optical Coherence Tomography | At Weeks 28 and 32 | 
| Average change from baseline in Central Subfield Thickness | Spectral Domain Optical Coherence Tomography | At Weeks 60 and 64 | 
| Number of visits with presence of Intraretinal Fluid and/or Subretinal Fluid, and sub-Retinal Pigment Epithelium fluid in the central subfield | Spectral Domain Optical Coherence Tomography | At Weeks 28 and 32 | 
| Number of visits with presence of Intraretinal Fluid and/or Subretinal Fluid, and sub-Retinal Pigment Epithelium fluid in the central subfield | Spectral Domain Optical Coherence Tomography | At Weeks 60 and 64 | 
| Change in Visual Function Questionnnaire-25 | Visual Function Questionnnaire-25 | At Weeks 32 and 64 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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macula damage, retina damage, dry macular degeneration, Age-related Macular Degeneration, Macular Degeneration, Wet Macular Degeneration, Retinal Degeneration, Retinal Diseases, Eye Diseases, AMD, nAMD, wet AMD, RTH258, Brolucizumab, double blind, age-related macular degeneration (ARMD), vision loss, Subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration