To Compare Brolucizumab to Aflibercept in Chinese Patients With Visual Impairment Due to Diabetic Macular Edema (KINGLET)

A One-Year, Randomized, Double-Masked, Multicenter, Phase III, Two-Arm Study Assessing the Efficacy and Safety of Brolucizumab Versus Aflibercept in Adult Chinese Patients With Visual Impairment Due to Diabetic Macular Edema

The purpose of this study was to evaluate the efficacy and safety of brolucizumab in treatment of Chinese patients with visual impairment due to Diabetic Macular Edema.

Study Overview

• Status: Completed
• Conditions: Diabetic Macular Edema
• Intervention / Treatment: Drug: Brolucizumab; Drug: Aflibercept

Detailed Description

The study is a randomized, double-masked, multi-center, active-controlled, 2-arm study in Chinese patients with Diabetic macular edema (DME). Approximately 335 Chinese patients were planned to be screened (20% screening failure rate expected) and approximately 268 (134 per arm) patients were planned to be randomized in approximately 25 centers.

Patients who met all the inclusion and none of the exclusion criteria were randomized in a 1:1 ratio to one of two treatment arms:

• Brolucizumab 6 mg: 5 × every 6 weeks (q6w) loading then every 12 weeks (q12w) or every 8 weeks (q8w) maintenance
• Aflibercept 2 mg: 5 × every 4 weeks (q4w) loading then q8w maintenance

Disease activity assessments (DAAs) were conducted by the masked investigator for both treatment arms at Weeks 32, 36, and 48. In the brolucizumab arm, subjects who qualified for q12w during this initial q12w interval continued on a q12w treatment frequency unless disease activity was identified at the subsequent DAA visit at Week 48, in which case subjects were switched to a q8w treatment interval until Week 52.

• Study Type: Interventional
• Enrollment (Actual): 266
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100044
    • Novartis Investigative Site
  • Beijing, China, 100730
    • Novartis Investigative Site
  • Beijing, China, 100034
    • Novartis Investigative Site
  • Beijing, China, 100191
    • Novartis Investigative Site
  • Chongqing, China, 400038
    • Novartis Investigative Site
  • Chongqing, China, 400042
    • Novartis Investigative Site
  • Nanjing, China, 210036
    • Novartis Investigative Site
  • Shanghai, China, 200031
    • Novartis Investigative Site
  • Shanghai, China, 200080
    • Novartis Investigative Site
  • Shanghai, China, 200092
    • Novartis Investigative Site
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Novartis Investigative Site
    • Shantou, Guangdong, China, 515041
      • Novartis Investigative Site
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150001
      • Novartis Investigative Site
  • Hubei
    • Wuhan, Hubei, China, 430070
      • Novartis Investigative Site
  • Jiangsu
    • Wuxi, Jiangsu, China, 214002
      • Novartis Investigative Site
  • Jilin
    • Changchun City, Jilin, China, 130041
      • Novartis Investigative Site
  • Shandong
    • Qingdao, Shandong, China, 2666000
      • Novartis Investigative Site
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Novartis Investigative Site
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Novartis Investigative Site
    • Tianjin, Tianjin, China, 300070
      • Novartis Investigative Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Novartis Investigative Site
    • Hangzhou, Zhejiang, China, 310003
      • Novartis Investigative Site
    • Hangzhou, Zhejiang, China, 310014
      • Novartis Investigative Site
    • Wenzhou, Zhejiang, China, 325027
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed informed consent must be obtained prior to participation in the study.
2. Patients ≥18 years of age at screening
3. Patients with type 1 or type 2 diabetes mellitus (DM) and Hemoglobin A1c (HbA1c) of ≤10% at screening
4. Medication for the management of diabetes must have been stable within 3 months prior to randomization and is expected to remain as stable as medically acceptable during the course of the study

5. Study Eye Visual impairment due to diabetic macular edema (DME) with:

   • Best-corrected visual acuity (BCVA) score between 78 and 23 letters, inclusive, using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) testing charts at a starting testing distance of 4 meters (approximate Snellen equivalent of 20/32 to 20/320) at screening and baseline
   • DME involving the center of the macula, with central subfield retinal thickness (e.g. measured from retinal pigment epithelium (RPE) to the inner limiting membrane (ILM) inclusively) of ≥320 μm on Spectral domain optical coherence tomography (SD-OCT) at screening.

Exclusion Criteria:

• Active Proliferative diabetic retinopathy (PDR) in the study eye as per investigator
• Concomitant conditions or ocular disorders in the study eye 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 medical or surgical intervention for the duration of the study (e.g. cataract, vitreous hemorrhage, retinal vascular occlusion, retinal detachment, macular hole, or choroidal neovascularization (CNV) of any cause)
• Any active intraocular or periocular infection or active intraocular inflammation (e.g. infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis, uveitis) in study eye at screening or baseline
• Structural damage of the fovea in the study eye at screening likely to preclude improvement in visual acuity following the resolution of macular edema (ME), including atrophy of the retinal pigment epithelium, subretinal fibrosis, laser scar(s), epiretinal membrane involving fovea or organized hard exudate plaques
• Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) > 25 mmHg on medication or according to investigator's judgment at Screening or Baseline
• Neovascularization of the iris in the study eye at screening or baseline
• Evidence of vitreomacular traction in the study eye at screening or baseline which in the opinion of the investigator, affects visual acuity
• Previous treatment with any anti-vascular growth factor (VEGF) drug or investigational drugs in the study eye

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brolucizumab 6 mg; 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance	Drug: Brolucizumab; 5 x every 6 weeks loading then every 12 weeks or every 8 weeks maintenance; Other Names: RTH258
Active Comparator: Aflibercept 2 mg; 5 x every 4 weeks loading then every 8 weeks maintenance	Drug: Aflibercept; 5 x every 4 weeks loading then every 8 weeks maintenance; Other Names: Eylea

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline at Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye.	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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.	Baseline to Week 52
Best-corrected Visual Acuity (BCVA) - Average Change From Baseline Over the Period Week 40 Through Week 52 for the Study Eye	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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.	Week 40 to Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline by Visit up to Week 52 in Best-corrected Visual Acuity (BCVA) for the Study Eye	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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.	Baseline, Week 52
Best-corrected Visual Acuity (BCVA) - Average Change From Baseline Over the Period Week 4 Through Week 52 for the Study Eye	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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.	Week 4 to Week 52
Best-corrected Visual Acuity (BCVA) - Average Change From Baseline Over the Period Week 20 Through Week 52 for the Study Eye	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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.	Week 20 to Week 52
Best-corrected Visual Acuity (BCVA) - Average Change From Baseline Over the Period Week 28 Through Week 52 for the Study Eye	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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.	Week 28 to Week 52
Time-to-first q8w Treatment Need: Summary for Brolucizumab Subjects by Disease Activity Assessment Visit	The estimate for the proportion of subjects with a positive q12w treatment status was derived from Kaplan Meier time-to-event analyses for the event 'first q8w-need', applying a 'q8w-need' allocation in case of missing or confounded data attributable to lack of efficacy and/or lack of safety. As a result, the probability that subjects in brolucizumab arm do not need a q8w treatment (and therefore are maintained on a q12w treatment) up to the visit is reported in the table.	Baseline (Week 0), Week 32, Week 36 and Week 48
Time-to-first q8w Treatment Need: Summary for Brolucizumab Subjects by Disease Activity Assessment Visit, Within Those Subjects With no q8w-need During the Initial q12w Cycle	The estimate for the proportion of subjects with a positive q12w treatment status was derived from Kaplan Meier time-to-event analyses for the event 'first q8w-need', applying a 'q8w-need' allocation in case of missing or confounded data attributable to lack of efficacy and/or lack of safety. As a result, the probability that subjects in brolucizumab arm do not need a q8w treatment (and therefore are maintained on a q12w treatment) up to the visit is reported in the table.	Week 36 and Week 48
Number and Percentage of Patients Who Gained in ≥5, ≥10 and ≥15 ETDRS Letters in BCVA From Baseline to Week 52 for the Study Eye	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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.	Baseline, Week 52
Time to Achieve Gain of >= 5 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain	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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.	Baseline up to Week 52
Time to Achieve Gain of >= 10 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain	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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.	Baseline up to Week 52
Time to Achieve Gain of >= 15 Letters in BCVA From Baseline or Reach BCVA >=84 Letters for the Study Eye - Probability of BCVA Gain	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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.	Baseline up to Week 52
Number and Percentage of Patients Who Lost ≥5, ≥10 and ≥15 ETDRS Letters in BCVA From Baseline to Week 52 for the Study Eye	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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.	Baseline, Week 52
Proportion of Patients Who Have Absolute BCVA ≥73 ETDRS Letters at Each Post-baseline Visit for the Study Eye	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. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.	Baseline up to Week 52
Number (%) of Subjects With q8w Treatment Need as Assessed by the Investigator at First Disease Activity Assessment (DAA) Visit - Week 32	To evaluate the efficacy related to dosing regimen of brolucizumab	Week 32
Number (%) of Subjects With q8w Treatment Need as Assessed by the Investigator at Week 36, and Week 48	To evaluate the efficacy related to dosing regimen of brolucizumab	Week 36, Week 48
Change From Baseline at Week 52 in Central Subfield Thickness (CSFT) for the Study Eye	Central Subfield Thickness Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center.	Baseline, Week 52
Average Change From Baseline Over the Period Week 40 Through Week 52 in Central Subfield Thickness (CSFT) for the Study Eye	Central Subfield Thickness Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center.	Baseline, over the period of Week 40 to Week 52
Average Change From Baseline Over the Period Week 4 Through Week 52 in Central Subfield Thickness (CSFT) for the Study Eye	Central Subfield Thickness Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center.	Baseline, over the period of Week 4 to Week 52
Number and Percentage of Patients Who Have CSFT (<280 Microns) at Each Assessment Visit for the Study Eye	Central Subfield Thickness Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center.	Baseline up to Week 52
Number (%) of Patients With Progression to Proliferative Diabetic Retinopathy (PDR) as Assessed by ETDRS DRSS of at Least 61 by Week 52 for the Study Eye Among the Subset of Non-PDR Subjects at Screening	As evaluated using the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (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 converted and categorized on a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR). A lower score represents better visual functioning.	Baseline, Week 52
Number (%) of Patients With Presence of Leakage in the Study Eye on Fluorescein Angiography (FA)	Assessed by angiography.	Week 52
Number (%) of Patients With Presence of Subretinal Fluid (SRF), Intraretinal Fluid (IRF) in the Study Eye	To evaluate the efficacy of brolucizumab relative to aflibercept over the time period by assessing changes in anatomical parameters	Baseline up to Week 52
Number of Patients With Presence of Subretinal Fluid (SRF) in the Study 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	Week 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52
Number of Patients With Presence of Intraretinal Fluid (IRF) in the Study 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	Week 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52
Intraretinal Fluid (IRF) Status in the Central Subfield: Proportion of Subjects With Presence of 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	Week 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52
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, Week 28 and Week 52
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.	Baseline, Week 28 and Week 52
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, Week 28 and Week 52
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.	Baseline, Week 28 and Week 52
Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Number of Subjects With >=2-step Worsening 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, Week 28 and Week 52
Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Proportion of Subjects With >=2-step Worsening 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.	Baseline, Week 28 and Week 52
Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Number of Subjects With >=3-step Worsening 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, Week 28 and Week 52
Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Proportion of Subjects With >=3-step Worsening 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.	Baseline, Week 28 and Week 52
Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - Overall 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, Week 28 and Week 52
Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - 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, Week 28 and Week 52
Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - 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, Week 28 and Week 52
Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - 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, Week 28 and Week 52
Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - 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, Week 28 and Week 52
Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - 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, Week 28 and Week 52
Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - 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, Week 28 and Week 52
Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - 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, Week 28 and Week 52
Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - 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, Week 28 and Week 52
Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - 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, Week 28 and Week 52
Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - 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, Week 28 and Week 52
Change From Baseline at Week 28 and Week 52 in Patient Reported Outcomes (Visual Function Questionnaire-25) - 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, Week 28 and Week 52
Brolucizumab Serum Concentration	To confirm the systemic brolucizumab exposure in a subset of patients.	Approximately 24 hours post Day 1 treatment and approximately 24 hours post Week 24 treatment
Number (%) of Patients Who Have Positive Anti-drug Antibody (ADA) Status in Brolucizumab Arm	To assess the immunogenicity of brolucizumab	Up to Week 52
Ocular Adverse Events (AEs) (>=2% 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 30days post treatment, up to a maximum duration of approximately 52 weeks.
Number of Subjects With Non-ocular Adverse Events (AEs) (>=2% in Any Treatment Arm)	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 30days post treatment, up to a maximum duration of approximately 52 weeks.

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): August 23, 2019
• Primary Completion (Actual): January 31, 2023
• Study Completion (Actual): January 31, 2023

Study Registration Dates

• First Submitted: August 14, 2019
• First Submitted That Met QC Criteria: August 14, 2019
• First Posted (Actual): August 15, 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: macular edema; diabetic retinopathy; aflibercept; Intravitreal injection; brolucizumab; Diabetic Macular edema (DME)
• Additional Relevant MeSH Terms: Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Sensation Disorders; Macular Edema; Edema; Vision, Low; Vision Disorders; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept
• Other Study ID Numbers: CRTH258B2304

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