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

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)

This 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.

Study Overview

• Status: Completed
• Conditions: Age-related Macular Degeneration
• Intervention / Treatment: Biological: Brolucizumab 6 mg; Biological: Aflibercept 2 mg

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 734
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Caba, Argentina, C1056
    • Novartis Investigative Site
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, 1116
      • Novartis Investigative Site
    • Ciudad Autonoma de Bs As, Buenos Aires, Argentina, C1015ABO
      • Novartis Investigative Site
  • De Santa Fe
    • Rosario, De Santa Fe, Argentina, B7602
      • Novartis Investigative Site
• Australia
  • New South Wales
    • Albury, New South Wales, Australia, 2640
      • Novartis Investigative Site
    • Hurstville, New South Wales, Australia, 2220
      • Novartis Investigative Site
    • Parramatta, New South Wales, Australia, 2150
      • Novartis Investigative Site
    • Sydney, New South Wales, Australia, 2000
      • Novartis Investigative Site
  • Queensland
    • Southport, Queensland, Australia, 4215
      • Novartis Investigative Site
  • Victoria
    • Glen Waverley, Victoria, Australia, 3150
      • Novartis Investigative Site
    • Rowville, Victoria, Australia, 3179
      • Novartis Investigative Site
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Novartis Investigative Site
• Austria
  • Vienna, Austria, 1090
    • Novartis Investigative Site
  • Wien, Austria, 1140
    • Novartis Investigative Site
• Belgium
  • Alken, Belgium, 3570
    • Novartis Investigative Site
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
• Canada
  • Quebec, Canada, G1S 4L8
    • Novartis Investigative Site
  • Ontario
    • Brampton, Ontario, Canada, L6Y 0P6
      • Novartis Investigative Site
    • London, Ontario, Canada, N6A 4G5
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M4N 3M5
      • Novartis Investigative Site
  • Quebec
    • Boisbriand, Quebec, Canada, J7H 1S6
      • Novartis Investigative Site
• Czechia
  • Ostrava Poruba, Czechia, 708 52
    • Novartis Investigative Site
  • Praha, Czechia, 12808
    • Novartis Investigative Site
  • Praha 10, Czechia, 100 34
    • Novartis Investigative Site
  • CZE
    • Hradec Kralove, CZE, Czechia, 500 05
      • Novartis Investigative Site
  • Czech Republic
    • Zlin, Czech Republic, Czechia, 762 75
      • Novartis Investigative Site
• France
  • Bordeaux, France, 33000
    • Novartis Investigative Site
  • Creteil, France, 94000
    • Novartis Investigative Site
  • Marseille, France, F 13008
    • Novartis Investigative Site
  • Montauban, France, 82000
    • Novartis Investigative Site
  • Nantes Cedex 1, France, 44093
    • Novartis Investigative Site
  • Paris, France, 75015
    • Novartis Investigative Site
  • Paris cedex 10, France, 75010
    • Novartis Investigative Site
  • Rueil Malmaison, France, 92500
    • Novartis Investigative Site
  • Strasbourg, France, 67000
    • Novartis Investigative Site
  • Indre Et Loire
    • Saint Cyr sur Loire, Indre Et Loire, France, 37540
      • Novartis Investigative Site
  • Rhone
    • Lyon cedex 04, Rhone, France, 69317
      • Novartis Investigative Site
• Germany
  • Berlin, Germany, 10713
    • Novartis Investigative Site
  • Bonn, Germany, 53105
    • Novartis Investigative Site
  • Duesseldorf, Germany, 40212
    • Novartis Investigative Site
  • Freiburg, Germany, 79106
    • Novartis Investigative Site
  • Gottingen, Germany, 37075
    • Novartis Investigative Site
  • Kempten, Germany, 87435
    • Novartis Investigative Site
  • Leipzig, Germany, 04103
    • Novartis Investigative Site
  • Mainz, Germany, 55131
    • Novartis Investigative Site
  • Muenster, Germany, 48149
    • Novartis Investigative Site
  • Muenster, Germany, 48145
    • Novartis Investigative Site
  • Ulm, Germany, 89075
    • Novartis Investigative Site
• Israel
  • Jerusalem, Israel, 9112001
    • Novartis Investigative Site
  • Ramat Gan, Israel, 52621
    • Novartis Investigative Site
  • Tel Aviv, Israel, 64239
    • Novartis Investigative Site
  • Zerifin, Israel, 6093000
    • Novartis Investigative Site
• Italy
  • Novara, Italy, 28100
    • Novartis Investigative Site
  • BO
    • Bologna, BO, Italy, 40138
      • Novartis Investigative Site
  • GE
    • Genova, GE, Italy, 16132
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20122
      • Novartis Investigative Site
    • Milano, MI, Italy, 20100
      • Novartis Investigative Site
  • PA
    • Palermo, PA, Italy, 90127
      • Novartis Investigative Site
  • PG
    • Perugia, PG, Italy, 06100
      • Novartis Investigative Site
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Novartis Investigative Site
  • Daegu, Korea, Republic of, 705703
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 05505
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 07301
    • Novartis Investigative Site
  • Gyeonggi Do
    • Bundang Gu, Gyeonggi Do, Korea, Republic of, 13620
      • Novartis Investigative Site
  • Seocho Gu
    • Seoul, Seocho Gu, Korea, Republic of, 06591
      • Novartis Investigative Site
• Malaysia
  • Melaka Malaysia
    • Melaka, Melaka Malaysia, Malaysia, 75000
      • Novartis Investigative Site
  • Selangor
    • Batu Caves, Selangor, Malaysia, 68100
      • Novartis Investigative Site
    • Shah Alam, Selangor, Malaysia, 40000
      • Novartis Investigative Site
• Netherlands
  • Hertogenbosch, Netherlands, 5200
    • Novartis Investigative Site
  • Nijmegen, Netherlands, 6525 EX
    • Novartis Investigative Site
• Portugal
  • Coimbra, Portugal, 3000 075
    • Novartis Investigative Site
  • Porto, Portugal, 4099-001
    • Novartis Investigative Site
  • Vila Franca de Xira, Portugal, 2600-009
    • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08025
    • Novartis Investigative Site
  • Barcelona, Spain, 08024
    • Novartis Investigative Site
  • Cordoba, Spain, 14012
    • Novartis Investigative Site
  • Zaragoza, Spain, 50009
    • Novartis Investigative Site
  • Cataluna
    • Barcelona, Cataluna, Spain, 08022
      • Novartis Investigative Site
  • Catalunya
    • Sant Cugat, Catalunya, Spain, 08190
      • Novartis Investigative Site
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Novartis Investigative Site
  • Valencia
    • Burjassot, Valencia, Spain, 46100
      • Novartis Investigative Site
• Sweden
  • Oerebro, Sweden, 701 85
    • Novartis Investigative Site
  • Vasteras, Sweden, 72189
    • Novartis Investigative Site
• Switzerland
  • Binningen, Switzerland, 4102
    • Novartis Investigative Site
• Taiwan
  • Taipei, Taiwan, 11217
    • Novartis Investigative Site
  • Taipei, Taiwan, 10449
    • Novartis Investigative Site
  • Taipei, Taiwan, 103616
    • Novartis Investigative Site
  • Taoyuan, Taiwan, 33305
    • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom, EC1V 2PD
    • Novartis Investigative Site
  • Rugby, United Kingdom, CV22 5PX
    • Novartis Investigative Site
  • Sunderland, United Kingdom, SR2 9HP
    • Novartis Investigative Site
  • Torquay, United Kingdom, TQ2 7AA
    • Novartis Investigative Site
  • Wolverhampton, United Kingdom, WV10 0QP
    • Novartis Investigative Site
  • West Yorkshire
    • Bradford, West Yorkshire, United Kingdom, BD9 6RJ
      • Novartis Investigative Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85020
      • Novartis Investigative Site
  • California
    • Huntington Beach, California, United States, 92647
      • Novartis Investigative Site
    • Loma Linda, California, United States, 92354
      • Novartis Investigative Site
    • Riverside, California, United States, 92505
      • Novartis Investigative Site
    • Santa Ana, California, United States, 92705
      • Novartis Investigative Site
  • Florida
    • Fort Lauderdale, Florida, United States, 33309
      • Novartis Investigative Site
    • Fort Myers, Florida, United States, 33912-7125
      • Novartis Investigative Site
    • Orlando, Florida, United States, 32789
      • Novartis Investigative Site
    • Pinellas Park, Florida, United States, 33782
      • Novartis Investigative Site
    • Winter Haven, Florida, United States, 33880
      • Novartis Investigative Site
  • Illinois
    • Springfield, Illinois, United States, 62704
      • Novartis Investigative Site
  • Indiana
    • Indianapolis, Indiana, United States, 46280
      • Novartis Investigative Site
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Novartis Investigative Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55435
      • Novartis Investigative Site
  • North Carolina
    • Hickory, North Carolina, United States, 28602
      • Novartis Investigative Site
  • Oregon
    • Portland, Oregon, United States, 97210
      • Novartis Investigative Site
    • Springfield, Oregon, United States, 97477
      • Novartis Investigative Site
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Novartis Investigative Site
  • Texas
    • Austin, Texas, United States, 78705
      • Novartis Investigative Site
    • Bellaire, Texas, United States, 77401
      • Novartis Investigative Site
    • Fort Worth, Texas, United States, 76104
      • Novartis Investigative Site
    • Houston, Texas, United States, 77030
      • Novartis Investigative Site
    • Houston, Texas, United States, 77025
      • Novartis Investigative Site
    • San Antonio, Texas, United States, 78240
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brolucizumab 6 mg; 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.	Biological: Brolucizumab 6 mg; Intra-vitreal injection; Other Names: RTH258
Active Comparator: Aflibercept 2 mg; 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	Biological: Aflibercept 2 mg; Intra-vitreal injection; Other Names: EYLEA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distribution of the Last Interval With no Disease Activity up to Week 32 - Study Eye	No disease activity is defined as no change in visual acuity and no change in other signs of the disease (e.g. Intraretinal Fluid (IRF), Subretinal Fluid (SRF), hemorrhage, leakage, etc.). Treatment interval distribution. Number (%) of subjects at 12/8/4-weeks intervals up to Week 32 for the study eye. If the study treatment is discontinued before Week 16, then the treatment interval is 4 weeks; otherwise. the last interval with no disease activity is used (if there was disease activity, the last interval is shortened by 4 weeks, down to a minimum of 4 weeks). If the duration of the last interval falls within the following ranges of (4-week, 8-week) or (8-week, 12-week) or ≥12-week then the floor value of these ranges was used.	Up to Week 32
Average Change From Baseline at Week 28 and Week 32 in Best-corrected Visual Acuity (BCVA) - Study Eye	BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning. Least squares mean estimate - for weeks 28 and 32 combined.	Baseline, Week 28 and Week 32

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distribution of the Last Interval With no Disease Activity up to Week 64 - Study Eye	No disease activity is defined as no change in visual acuity and no change in other signs of the disease (e.g. IRF, SRF, hemorrhage, leakage, etc.). Treatment interval distribution. The number of subjects at 16/12/8/4-weeks intervals as the last interval with no disease activity. If the study treatment is discontinued before Week 16, then the treatment interval is 4 weeks; otherwise. the last interval with no disease activity is used (if there was disease activity, the last interval is shortened by 4 weeks, down to a minimum of 4 weeks). If the duration of the last interval falls within the following ranges of (4-week, 8-week) or (8-week, 12-week) or (12-weeks, 16-weeks) or ≥16-week then the floor value of these ranges was used.	Up to Week 64
Distribution of the Maximal Intervals With no Disease Activity up to Week 64 - Study Eye	No disease activity is defined as no change in visual acuity and no change in other signs of the disease (e.g. IRF, SRF, hemorrhage, leakage, etc.). Maximal interval distribution. Number of subjects at 16/12/8/4-weeks intervals as the last interval with no disease activity. If the study treatment is discontinued before Week 16 included, then the treatment interval is 4 weeks; otherwise, the last interval with no disease activity is used (if there was disease activity, the last interval is shortened by 4 weeks, down to a minimum of 4 weeks). If the duration of the maximal interval falls within the following ranges of [4-weeks, 8-weeks) or [8-weeks, 12-weeks) or [12-weeks, 16-weeks] or ≥16-weeks then the floor value of these ranges is used.	Up to Week 64
Number of Participants With no Disease Activity - Study Eye	Disease activity assessment as determined by visual acuity and assessment of other signs of the disease (e.g. IRF, SRF, hemorrhage, leakage, etc.).	Weeks 14 and 16
Time From Last Loading Injection to First Visit With No Disease Activity (Weeks) - 75th Percentile - Study Eye	Intraretinal fluid (IRF) and subretinal fluid (SRF) were assessed by Spectral Domain Optical Coherence Tomography (SD-OCT) (study eye). Please note that this endpoint can be impacted by the optional disease activity assessment visits and the flexible dosing regimen, in addition to the randomized treatment. Hence, the observed treatment effect may be confounded by the study design artifacts.	Up to Week 64
Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye	Intraretinal fluid (IRF) and subretinal fluid (SRF) were assessed by Spectral Domain Optical Coherence Tomography (SD-OCT) (study eye).	Up to Week 64
Average Change From Baseline at Week 60 and Week 64 in Best-corrected Visual Acuity (BCVA) - Study Eye	BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning. Least squares mean estimate - for weeks 60 and 64 combined.	Baseline, Week 60 and Week 64
Number of Participants With Best-corrected Visual Acuity Improvements of ≥ 15 Letters in BCVA From Baseline or Reached BCVA ≥ 84 Letters up to Week 32/64 Per Treatment Arm - Study Eye	BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.	Baseline, Week 32, and Week 64
Number of Participants With Best-corrected Visual Acuity ≥ 69 Letters - Study Eye	BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.	Week 32 and Week 64
Average Change From Baseline in Central Subfield Thickness (CSFT) - Study Eye	CSFT was measured by Spectral Domain Optical Coherence Tomography	Baseline, Weeks 28 and 32 and at Weeks 60 and 64
Number of Participants With Presence of Intraretinal Fluid and/or Subretinal Fluid in the Central Subfield - Study Eye	Intraretinal Fluid and/or Subretinal Fluid status was measured by Spectral Domain Optical Coherence Tomography (SD-OCT).	At Weeks 28, 32, 60 and 64
Number of Participants With Presence of Sub-Retinal Pigment Epithelium Fluid in the Central Subfield - Study Eye	Sub-Retinal Pigment Epithelium fluid status was measured by Spectral Domain Optical Coherence Tomography (SD-OCT).	At Weeks 28, 32, 60 and 64
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Composite Scores - Study Eye	The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales.	Baseline, Week 32, and Week 64
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - General Vision - Study Eye	The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales.	Baseline, Week 32, and Week 64
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Ocular Pain - Study Eye	The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales.	Baseline, Week 32, and Week 64
Change From Baseline n Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Near Activities - Study Eye	The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales.	Baseline, Week 32, and Week 64
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Distance Activities - Study Eye	The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales.	Baseline, Week 32, and Week 64
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Social Functioning - Study Eye	The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning or outcome. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales.	Baseline, Week 32, and Week 64
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Mental Health - Study Eye	The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning or outcome. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales.	Baseline, Week 32, and Week 64
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Role Difficulties - Study Eye	The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning or outcome. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales.	Baseline, Week 32, and Week 64
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Dependency - Study Eye	The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning or outcome. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales.	Baseline, Week 32, and Week 64
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Driving - Study Eye	The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales.	Baseline, Week 32, and Week 64
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Color Vision - Study Eye	The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales.	Baseline, Week 32, and Week 64
Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Peripheral Vision - Study Eye	The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains. The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. Each subscale score has a range of 0 to 100 inclusive and will be calculated from the re-scaled raw data. A composite score is derived based on the average of the 11 subscales.	Baseline, Week 32, and Week 64
Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye	An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign (including abnormal laboratory findings), symptom or disease) in a subject or clinical investigation subject.	Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 483 days, approx. 69 weeks, 1.3 years.
Number of Participants With Treatment Emergent Non-ocular Adverse Events (Greater Than or Equal to 2% in Any Treatment Arm) - Summary Table	An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign (including abnormal laboratory findings), symptom or disease) in a subject or clinical investigation subject.	Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 483 days, approx. 69 weeks, 1.3 years.

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on www.novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2019
• Primary Completion (Actual): September 9, 2022
• Study Completion (Actual): September 9, 2022

Study Registration Dates

• First Submitted: July 1, 2019
• First Submitted That Met QC Criteria: July 1, 2019
• First Posted (Actual): July 2, 2019

Study Record Updates

• Last Update Posted (Actual): October 9, 2024
• Last Update Submitted That Met QC Criteria: October 7, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Eye Diseases; AMD; vision loss; double blind; Age-related Macular Degeneration; Retinal Diseases; Macular Degeneration; wet AMD; Retinal Degeneration; age-related macular degeneration (ARMD); macula damage; retina damage; dry macular degeneration; Wet Macular Degeneration; nAMD; Brolucizumab; Subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration; RTH258
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept
• Other Study ID Numbers: CRTH258A2303; 2019-000716-28 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No