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

Age-related Macular Degeneration Clinical Trial

— TALON  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04005352
• Other study ID #: CRTH258A2303
• Secondary ID: 2019-000716-28
• Status: Completed
• Phase: Phase 3
• Start date: September 25, 2019
• Est. completion date: September 9, 2022

Study information

• Verified date: January 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 734
• Est. completion date: September 9, 2022
• Est. primary completion date: September 9, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Age-related Macular Degeneration
• Macular Degeneration

Intervention

Biological:
• Brolucizumab 6 mg
Intra-vitreal injection
• Aflibercept 2 mg
Intra-vitreal injection

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Caba
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Ciudad Autonoma de Bs As	Buenos Aires
Argentina	Novartis Investigative Site	Rosario	De Santa Fe
Australia	Novartis Investigative Site	Albury	New South Wales
Australia	Novartis Investigative Site	Glen Waverley	Victoria
Australia	Novartis Investigative Site	Hurstville	New South Wales
Australia	Novartis Investigative Site	Nedlands	Western Australia
Australia	Novartis Investigative Site	Parramatta	New South Wales
Australia	Novartis Investigative Site	Rowville	Victoria
Australia	Novartis Investigative Site	Southport	Queensland
Australia	Novartis Investigative Site	Sydney	New South Wales
Austria	Novartis Investigative Site	Vienna
Austria	Novartis Investigative Site	Wien
Belgium	Novartis Investigative Site	Alken
Belgium	Novartis Investigative Site	Leuven
Canada	Novartis Investigative Site	Boisbriand	Quebec
Canada	Novartis Investigative Site	Brampton	Ontario
Canada	Novartis Investigative Site	London	Ontario
Canada	Novartis Investigative Site	Quebec
Canada	Novartis Investigative Site	Toronto	Ontario
Czechia	Novartis Investigative Site	Hradec Kralove	CZE
Czechia	Novartis Investigative Site	Ostrava Poruba
Czechia	Novartis Investigative Site	Praha
Czechia	Novartis Investigative Site	Praha 10
Czechia	Novartis Investigative Site	Zlin	Czech Republic
France	Novartis Investigative Site	Bordeaux
France	Novartis Investigative Site	Creteil
France	Novartis Investigative Site	Lyon cedex 04	Rhone
France	Novartis Investigative Site	Marseille
France	Novartis Investigative Site	Montauban
France	Novartis Investigative Site	Nantes Cedex 1
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Paris cedex 10
France	Novartis Investigative Site	Rueil Malmaison
France	Novartis Investigative Site	Saint Cyr sur Loire	Indre Et Loire
France	Novartis Investigative Site	Strasbourg
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bonn
Germany	Novartis Investigative Site	Duesseldorf
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Gottingen
Germany	Novartis Investigative Site	Kempten
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	Ulm
Israel	Novartis Investigative Site	Jerusalem
Israel	Novartis Investigative Site	Ramat Gan
Israel	Novartis Investigative Site	Tel Aviv
Israel	Novartis Investigative Site	Zerifin
Italy	Novartis Investigative Site	Bologna	BO
Italy	Novartis Investigative Site	Genova	GE
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Novara
Italy	Novartis Investigative Site	Palermo	PA
Italy	Novartis Investigative Site	Perugia	PG
Korea, Republic of	Novartis Investigative Site	Bundang Gu	Gyeonggi Do
Korea, Republic of	Novartis Investigative Site	Busan
Korea, Republic of	Novartis Investigative Site	Daegu
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul	Seocho Gu
Malaysia	Novartis Investigative Site	Batu Caves	Selangor
Malaysia	Novartis Investigative Site	Melaka	Melaka Malaysia
Malaysia	Novartis Investigative Site	Shah Alam	Selangor
Netherlands	Novartis Investigative Site	Hertogenbosch
Netherlands	Novartis Investigative Site	Nijmegen
Portugal	Novartis Investigative Site	Coimbra
Portugal	Novartis Investigative Site	Porto
Portugal	Novartis Investigative Site	Vila Franca de Xira
Spain	Novartis Investigative Site	Barcelona	Cataluna
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Burjassot	Valencia
Spain	Novartis Investigative Site	Cordoba
Spain	Novartis Investigative Site	Pamplona	Navarra
Spain	Novartis Investigative Site	Sant Cugat	Catalunya
Spain	Novartis Investigative Site	Zaragoza
Sweden	Novartis Investigative Site	Oerebro
Sweden	Novartis Investigative Site	Vasteras
Switzerland	Novartis Investigative Site	Binningen
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taoyuan
United Kingdom	Novartis Investigative Site	Bradford	West Yorkshire
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Rugby
United Kingdom	Novartis Investigative Site	Sunderland
United Kingdom	Novartis Investigative Site	Torquay
United Kingdom	Novartis Investigative Site	Wolverhampton
United States	Novartis Investigative Site	Austin	Texas
United States	Novartis Investigative Site	Bellaire	Texas
United States	Novartis Investigative Site	Fort Lauderdale	Florida
United States	Novartis Investigative Site	Fort Myers	Florida
United States	Novartis Investigative Site	Fort Worth	Texas
United States	Novartis Investigative Site	Germantown	Tennessee
United States	Novartis Investigative Site	Hickory	North Carolina
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Huntington Beach	California
United States	Novartis Investigative Site	Indianapolis	Indiana
United States	Novartis Investigative Site	Loma Linda	California
United States	Novartis Investigative Site	Minneapolis	Minnesota
United States	Novartis Investigative Site	Orlando	Florida
United States	Novartis Investigative Site	Phoenix	Arizona
United States	Novartis Investigative Site	Pinellas Park	Florida
United States	Novartis Investigative Site	Portland	Oregon
United States	Novartis Investigative Site	Riverside	California
United States	Novartis Investigative Site	San Antonio	Texas
United States	Novartis Investigative Site	Santa Ana	California
United States	Novartis Investigative Site	Springfield	Oregon
United States	Novartis Investigative Site	Springfield	Illinois
United States	Novartis Investigative Site	West Des Moines	Iowa
United States	Novartis Investigative Site	Winter Haven	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Canada,  Czechia,  France,  Germany,  Israel,  Italy,  Korea, Republic of,  Malaysia,  Netherlands,  Portugal,  Spain,  Sweden,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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.
Secondary	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.