Study of Efficacy and Safety of Brolucizumab vs. Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema

Diabetic Macular Edema Clinical Trial

— KESTREL  

Official title:

A Two-year, Three-arm, Randomized, Double-masked, Multicenter, Phase III Study Assessing the Efficacy and Safety of Brolucizumab Versus Aflibercept in Adult Patients With Visual Impairment Due to Diabetic Macular Edema

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03481634
• Other study ID #: CRTH258B2301
• Secondary ID: 2017-004742-23
• Status: Completed
• Phase: Phase 3
• Start date: July 23, 2018
• Est. completion date: October 18, 2021

Study information

• Verified date: January 2023
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to evaluate the efficacy and safety of brolucizumab in treatment of patients with visual impairment due to diabetic macular edema (DME).

Description:

This was a Phase III, randomized, double-masked, multi-center, active-controlled, three-arm study designed to evaluate the efficacy and safety of brolucizumab 6 mg and 3 mg compared to the active control, aflibercept 2 mg used per authorized label, in subjects with diabetic macular edema (DME). The study included a screening period of up to 2 weeks to assess eligibility, followed by a doublemasked treatment period (Day 1 to Week 96). The baseline visit was defined as Day 1/Visit 1, and end of treatment visit as Visit 27 (Week 96). After the last treatment visit, a post-treatment follow-up period was planned from Week 96 to Week 100. Subjects were assigned to one of three treatment arms in a 1:1:1 ratio: brolucizumab 6 mg/0.05 mL administered 5 x every 6 weeks (q6w) during loading phase then q12w/every 8 weeks (q8w) during maintenance phase, brolucizumab 3 mg/0.05 mL administered 5 x every 6 weeks (q6w) during loading phase then q12w/q8w during maintenance phase or aflibercept 2 mg/0.05 mL administered 5 x every 4 weeks (q4w) during loading phase then q8w during maintenance phase. Disease Activity Assessments (DAAs) were conducted by the masked investigator for each treatment arm at Week 32 and Week 36, i.e. 8 and 12 weeks after the end of the loading phase for subjects receiving brolucizumab. Assessments were also performed at Week 48, and will then continue to be performed from Week 60 up to Week 96, every 12 weeks. Subjects in the brolucizumab arms who qualified for q12w during the initial q12w interval continued on a q12w treatment frequency unless disease activity was identified at any of the subsequent DAA visits, in which case subjects were switched to a q8w treatment interval until the end of the study. To fulfil the double-masking requirement, each investigational site had masked and unmasked staff. The investigator who performed the injection was unmasked to the treatments as were any other site personnel who had been delegated responsibility for working with the Investigational Product (IP). The unmasked site personnel and unmasked injecting investigator did not perform Best-corrected visual acuity (BCVA), complete ophthalmic examination (with the exception of post-injection safety assessment), DAAs or administer the Visual Functioning Questionnaire-25 (VFQ-25). Also, the unmasked site personnel and unmasked injecting physician did not perform assessment of any ocular or non-ocular safety parameters, or assess causality of Adverse event (AEs) for subjects during the course of the study except an event reported immediately following Intravitreal treatment (IVT). Once the designated roles were determined, the unmasked investigator/site personnel roles were not switched at any time after randomization to masked role. Every effort was made to limit the number of unmasked study personnel to ensure the integrity of this masked study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 566
• Est. completion date: October 18, 2021
• Est. primary completion date: November 11, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Written informed consent before any assessment
• Patients with type 1 or type 2 diabetes mellitus and HbA1c of =10% at screening
• Medication for the management of diabetes stable within 3 months prior to randomization and is expected to remain stable during the course of the study

Exclusion Criteria:

• Active proliferative diabetic retinopathy in the study eye
• Active intraocular or periocular infection or active intraocular inflammation in study eye
• Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) > 25 millimeters mercury (mmHg)
• Previous treatment with anti-VEGF drugs or investigational drugs in the study eye
• Stroke or myocardial infarction during the 6-month period prior to baseline
• Uncontrolled blood pressure defined as a systolic value =160 mmHg or diastolic value =100 mmHg Other protocol-specified inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Diabetic Macular Edema
• Edema
• Macular Edema
• Vision Disorders
• Vision, Low

Intervention

Drug:
• Brolucizumab
Intravitreal injection
• Aflibercept
Intravitreal injection

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Caba
Argentina	Novartis Investigative Site	Caba
Argentina	Novartis Investigative Site	Ciudad Autonoma de Bs As	Buenos Aires
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative Site	Rosario	Provincia De Santa Fe
Australia	Novartis Investigative Site	Adelaide	South Australia
Australia	Novartis Investigative Site	Clayton	Victoria
Australia	Novartis Investigative Site	Liverpool	New South Wales
Australia	Novartis Investigative Site	Melbourne	Victoria
Australia	Novartis Investigative Site	Nedlands	Western Australia
Australia	Novartis Investigative Site	Parramatta	New South Wales
Australia	Novartis Investigative Site	Sydney	New South Wales
Australia	Novartis Investigative Site	Westmead	New South Wales
Austria	Novartis Investigative Site	Graz
Austria	Novartis Investigative Site	Innsbruck
Austria	Novartis Investigative Site	Vienna
Canada	Novartis Investigative Site	Ottawa	Ontario
Canada	Novartis Investigative Site	Quebec
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
Colombia	Novartis Investigative Site	Bogota
Colombia	Novartis Investigative Site	Medellin	Antioquia
Colombia	Novartis Investigative Site	Medellin	Antioquia
Israel	Novartis Investigative Site	Haifa
Israel	Novartis Investigative Site	Haifa
Israel	Novartis Investigative Site	Haifa
Israel	Novartis Investigative Site	Jerusalem
Israel	Novartis Investigative Site	Kfar Saba
Israel	Novartis Investigative Site	Petach Tikva
Israel	Novartis Investigative Site	Rehovot
Israel	Novartis Investigative Site	Tel Aviv
Italy	Novartis Investigative Site	Catania	CT
Italy	Novartis Investigative Site	Chieti	CH
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Padova	PD
Italy	Novartis Investigative Site	Roma	RM
Japan	Novartis Investigative Site	Amagasaki city	Hyogo
Japan	Novartis Investigative Site	Chiyoda-ku	Tokyo
Japan	Novartis Investigative Site	Hachioji-city	Tokyo
Japan	Novartis Investigative Site	Ishioka	Ibaraki
Japan	Novartis Investigative Site	Kagoshima city	Kagoshima
Japan	Novartis Investigative Site	Kumamoto
Japan	Novartis Investigative Site	Kurume-city	Fukuoka
Japan	Novartis Investigative Site	Matsumoto-city	Nagano
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Nagoya-city	Aichi
Japan	Novartis Investigative Site	Osaka
Japan	Novartis Investigative Site	Saitama-shi	Saitama
Japan	Novartis Investigative Site	Shimotsuke	Tochigi
Japan	Novartis Investigative Site	Shinjuku ku	Tokyo
Japan	Novartis Investigative Site	Taito-ku	Tokyo
Japan	Novartis Investigative Site	Tsuchiura	Ibaragi
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Rotterdam
Netherlands	Novartis Investigative Site	Tilburg
Portugal	Novartis Investigative Site	Coimbra
Portugal	Novartis Investigative Site	Coimbra
Portugal	Novartis Investigative Site	Leiria
Portugal	Novartis Investigative Site	Porto
Portugal	Novartis Investigative Site	Porto
Portugal	Novartis Investigative Site	Santa Maria da Feira
Portugal	Novartis Investigative Site	Vila Franca de Xira
Puerto Rico	Novartis Investigative Site	Arecibo
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Sant Cugat	Catalunya
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Valladolid	Castilla Y Leon
Spain	Novartis Investigative Site	Zaragoza
United Kingdom	Novartis Investigative Site	Birmingham
United Kingdom	Novartis Investigative Site	Frimley	Surrey
United Kingdom	Novartis Investigative Site	Hull
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Nottingham
United States	Novartis Investigative Site	'Aiea	Hawaii
United States	Novartis Investigative Site	Austin	Texas
United States	Novartis Investigative Site	Austin	Texas
United States	Novartis Investigative Site	Austin	Texas
United States	Novartis Investigative Site	Bellaire	Texas
United States	Novartis Investigative Site	Beverly Hills	California
United States	Novartis Investigative Site	Cincinnati	Ohio
United States	Novartis Investigative Site	Cleveland	Ohio
United States	Novartis Investigative Site	Cleveland	Ohio
United States	Novartis Investigative Site	Colorado Springs	Colorado
United States	Novartis Investigative Site	Danbury	Connecticut
United States	Novartis Investigative Site	Harlingen	Texas
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Indianapolis	Indiana
United States	Novartis Investigative Site	Kingston	Pennsylvania
United States	Novartis Investigative Site	La Jolla	California
United States	Novartis Investigative Site	Leawood	Kansas
United States	Novartis Investigative Site	Lenexa	Kansas
United States	Novartis Investigative Site	Madison	Wisconsin
United States	Novartis Investigative Site	Memphis	Tennessee
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Mountain View	California
United States	Novartis Investigative Site	Nashville	Tennessee
United States	Novartis Investigative Site	New Albany	Indiana
United States	Novartis Investigative Site	Paducah	Kentucky
United States	Novartis Investigative Site	Pensacola	Florida
United States	Novartis Investigative Site	Philadelphia	Pennsylvania
United States	Novartis Investigative Site	Phoenix	Arizona
United States	Novartis Investigative Site	Reno	Nevada
United States	Novartis Investigative Site	San Antonio	Texas
United States	Novartis Investigative Site	Santa Barbara	California
United States	Novartis Investigative Site	Silverdale	Washington
United States	Novartis Investigative Site	Spokane	Washington
United States	Novartis Investigative Site	Springfield	Massachusetts
United States	Novartis Investigative Site	Stoneham	Massachusetts
United States	Novartis Investigative Site	Stuart	Florida
United States	Novartis Investigative Site	Tyler	Texas
United States	Novartis Investigative Site	Urbana	Illinois
United States	Novartis Investigative Site	Wheaton	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Canada,  Colombia,  Israel,  Italy,  Japan,  Netherlands,  Portugal,  Puerto Rico,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Best-corrected Visual Acuity (BCVA) at Week 52	BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts.; Visual Function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score of 78 to 23 (approximate Snellen equivalent of 20/32 to 20/320) in the study eye were included.; Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.; This endpoint was analyzed via the pairwise ANOVA method where the 2 dose groups of Brolucizumab are compared to Aflibercept.	Baseline, Week 52
Secondary	Average Change From Baseline in BCVA Over the Period Week 40 Through Week 52	BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts.; Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score of 78 to 23 (per the inclusion criteria) (approximate Snellen equivalent of 20/32 to 20/320) in the study eye were included.; Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.; This endpoint was analyzed via the pairwise ANOVA method where the 2 dose groups of Brolucizumab are compared to Aflibercept.	Baseline and Week 40 through Week 52 (average)
Secondary	Patients Maintained at q12w - Probability of Maintaining on q12w	Positive treatment status is defined as intravitreal (IVT) injections per planned dosing regimen [every 12 weeks (q12w)]. This outcome measure is pre-specified for brolucizumab treatment arms only.	Baseline (Week 0), Weeks 32, 36 and 48
Secondary	Patients Maintained at q12w (for Those Patients Who Qualified for q12w at Week 36) - Probability of Maintaining on q12w	Positive treatment status is defined as intravitreal (IVT) injections per planned dosing regimen [every 8 weeks (q8w)]. This outcome measure is pre-specified for brolucizumab treatment arms only.	Weeks 36 and 48
Secondary	Change From Baseline in BCVA at Each Visit up to Week 52	BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts.; Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score of 78 to 23 (approximate Snellen equivalent of 20/32 to 20/320) in the study eye were included.; Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.	Baseline (Week 0), Weeks 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Secondary	BCVA (Letters Read): ANOVA Results for Average Change From Baseline Over the Period Week 88 Through Week 100 for the Study Eye (FAS - LOCF)	Visual acuity was assessed at every study visit using best correction determined from protocol refraction (BCVA). BCVA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts.; LS Mean estimates are reported, comparing the 2 Brolucizumab arms to Aflibercept. Results do not apply to the Brolucizumab 6 mg arm when Brolucizumab 3mg is compared to Aflibercept. Likewise, results do not apply to the Brolucizumab 3 mg arm when Brolucizumab 6 mg is compared to Aflibercept.	Baseline, and Week 88 through Week 100 (average)
Secondary	Patients Maintained at q12w up to Week 64 (After Three q12w- Treatment Intervals) and Week 100 - Probability of Maintaining on q12w	This outcome measure is pre-specified for brolucizumab treatment arms only	Baseline (Week 0), Weeks 32, 36, 48, 60, 72, 84, and 96
Secondary	Secondary: Patients Maintained at q12w up to Week 64 (After Three q12w- Treatment Intervals) and Week 100, Within Those Patients That Qualified for q12w at Week 36 - Probability of Maintaining on q12w	This outcome measure is pre-specified for brolucizumab treatment arms only	Baseline (Week 0), Weeks 32, 36, 48, 60, 72, 84, and 96
Secondary	Change From Baseline in Central Subfield Thickness (CSFT) at Each Visit up to Week 52 - Pairwise ANOVA Results	Central Subfield Thickness Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center.; LS Mean estimates are reported, comparing the 2 Brolucizumab arms to Aflibercept. Results do not apply to the Brolucizumab 6 mg arm when Brolucizumab 3mg is compared to Aflibercept. Likewise, results do not apply to the Brolucizumab 3 mg arm when Brolucizumab 6 mg is compared to Aflibercept.	Baseline up to week 52
Secondary	Central Subfield Thickness (CSFT) (Micrometers): ANOVA Results for Average Change From Baseline Over the Period Week 88 Through Week 100 for the Study Eye (Full Analysis Set - LOCF)	Central subfield thickness (average thickness of circular 1mm area centered around fovea measured from RPE to ILM, inclusively). Assessed with Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts.; LS Mean estimates are reported, comparing the 2 Brolucizumab arms to Aflibercept. Results do not apply to the Brolucizumab 6 mg arm when Brolucizumab 3mg is compared to Aflibercept. Likewise, results do not apply to the Brolucizumab 3 mg arm when Brolucizumab 6 mg is compared to Aflibercept.	Baseline, and Week 88 through Week 100 (average)
Secondary	Number of Patients With Presence of Subretinal Fluid (SRF) at Each Assessment Visit	Subretinal Fluid (SRF) status in the central subfield: proportion of subjects with presence of SRF in the study eye by visit	Baseline up to Week 52 and Week 100
Secondary	Number of Patients With Presence of Intraretinal Fluid (IRF) at Each Assessment Visit	Intraretinal Fluid (IRF) status in the central subfield: proportion of subjects with presence of IRF in the study eye by visit	Baseline, up to Week 52 and Week 100
Secondary	Number of Patients With Presence of SRF and/or IRF in the Study Eye by Visit	Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) status in the central subfield: proportion of subjects with presence of SRF and/or IRF in the study eye by visit	Baseline, up to Week 52 and Week 100
Secondary	Number of Patients With Presence of Leakage on Fluorescein Angiography (FA) at Week 52	Assessed by angiography.	Week 52
Secondary	Number of Patients With Presence of Leakage on Fluorescein Angiography (FA) at Week 100	Assessed by angiography.	Week 100
Secondary	Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Number of Subjects With >=2-step Improvement From Baseline in the DRSS Score at Each Assessment Visit for the Study Eye - Number of Subjects	Severity of Diabetic Retinopathy (DR) was evaluated using the ETDRS DRSS score assessed by the Central Reading Center (CRC) based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were categorized on a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR). A lower score represents better visual functioning.	Baseline, Weeks 28, 52, 76, 100
Secondary	Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Proportion of Subjects With >=2-step Improvement From Baseline in the DRSS Score at Each Assessment Visit for the Study Eye - Percentage Estimates	Severity of Diabetic Retinopathy (DR) was evaluated using the ETDRS DRSS score assessed by the Central Reading Center (CRC) based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were categorized on a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR). A lower score represents better visual functioning.; estimates are reported, comparing the 2 Brolucizumab arms to Aflibercept. Results do not apply to the Brolucizumab 6 mg arm when Brolucizumab 3mg is compared to Aflibercept. Likewise, results do not apply to the Brolucizumab 3 mg arm when Brolucizumab 6 mg is compared to Aflibercept.; estimates represent the % of participants who were estimated to have a ">=2-step Improvement From Baseline in the DRSS Score" from pairwise logistic regression models adjusting for baseline DRSS score categories (<=4, =5), age categories (<65, =65 years) and treatment as fixed effect factors.; Abbreviation: Proportion Estimates = P.E.	Baseline, Weeks 28, 52, 76, 100
Secondary	Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Number of Subjects With >=3-step Improvement From Baseline in the DRSS Score at Each Assessment Visit for the Study Eye - Number of Subjects	Severity of Diabetic Retinopathy (DR) was evaluated using the ETDRS DRSS score assessed by the Central Reading Center (CRC) based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were categorized on a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR). A lower score represents better visual functioning.	Baseline, Weeks 28, 52, 76, 100
Secondary	Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Proportion of Subjects With >=3-step Improvement From Baseline in the DRSS Score at Each Assessment Visit for the Study Eye - Percentage Estimates	Severity of Diabetic Retinopathy (DR) was evaluated using the ETDRS DRSS score assessed by the Central Reading Center (CRC) based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were categorized on a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR). A lower score represents better visual functioning.; estimates are reported, comparing the 2 Brolucizumab arms to Aflibercept. Results do not apply to the Brolucizumab 6 mg arm when Brolucizumab 3mg is compared to Aflibercept. Likewise, results do not apply to the Brolucizumab 3 mg arm when Brolucizumab 6 mg is compared to Aflibercept.; estimates represent the % of participants who were estimated to have a ">=3-step Improvement From Baseline in the DRSS Score" from pairwise logistic regression models adjusting for baseline DRSS score categories (<=4, =5), age categories (<65, =65 years) and treatment as fixed effect factors.; Abbreviation: Proportion Estimates = P.E.	Baseline, Weeks 28, 52, 76, 100
Secondary	Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Composite Score	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. A composite score is derived based on the average of the 11 subscales.	Baseline, Weeks 28, 52, 76, 100
Secondary	Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - General Vision	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. A composite score is derived based on the average of the 11 subscales.	Baseline, Weeks 28, 52, 76, 100
Secondary	Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Ocular Pain	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. A composite score is derived based on the average of the 11 subscales.	Baseline, Weeks 28, 52, 76, 100
Secondary	Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Near Activities	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. A composite score is derived based on the average of the 11 subscales.	Baseline, Weeks 28, 52, 76, 100
Secondary	Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Distance Activities	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. A composite score is derived based on the average of the 11 subscales.	Baseline, Weeks 28, 52, 76, 100
Secondary	Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Social Functioning	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. A composite score is derived based on the average of the 11 subscales.	Baseline, Weeks 28, 52, 76, 100
Secondary	Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Mental Health	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. A composite score is derived based on the average of the 11 subscales.	Baseline, Weeks 28, 52, 76, 100
Secondary	Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Role Difficulties	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. A composite score is derived based on the average of the 11 subscales.	Baseline, Weeks 28, 52, 76, 100
Secondary	Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Dependency	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. A composite score is derived based on the average of the 11 subscales.	Baseline, Weeks 28, 52, 76, 100
Secondary	Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Driving	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. A composite score is derived based on the average of the 11 subscales.	Baseline, Weeks 28, 52, 76, 100
Secondary	Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Color Vision	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. A composite score is derived based on the average of the 11 subscales.	Baseline, Weeks 28, 52, 76, 100
Secondary	Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Peripheral Vision	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. A composite score is derived based on the average of the 11 subscales.	Baseline, Weeks 28, 52, 76, 100
Secondary	Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - General Health Rating	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. A composite score is derived based on the average of the 11 subscales.	Baseline, Weeks 28, 52, 76, 100
Secondary	Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye		Adverse events were reported from first dose of study treatment until Week 96, plus 30 days post treatment, up to a maximum duration of 100 weeks.
Secondary	Number of Subjects With Non-ocular Adverse Events (AEs) (>=2% in Any Treatment Arm)		Adverse events were reported from first dose of study treatment until Week 96, plus 30 days post treatment, up to a maximum duration of 100 weeks.

External Links

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