Study of Efficacy and Safety of Brolucizumab vs. Aflibercept in Chinese Patients With Neovascular Age-Related Macular Degeneration

A Twelve-Month, Randomized, Double-Masked, Multicenter, Phase III, Two-Arm Study Comparing the Efficacy and Safety of Brolucizumab 6 mg Versus Aflibercept in Chinese Patients With Neovascular Age-Related Macular Degeneration

To compare brolucizumab to aflibercept in Chinese patients with untreated active choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD)

Study Overview

• Status: Completed
• Conditions: Neovascular Age-Related Macular Degeneration
• Intervention / Treatment: Drug: Brolucizumab 6mg; Drug: Aflibercept 2 mg

Detailed Description

This was a randomized, double-masked, multicenter, parallel-group, active-controlled study. The study included 14 scheduled visits over 48 weeks. After confirmation of eligibility at baseline, participants were randomized in a 1:1 ratio to one of the 2 treatment arms:

• Brolucizumab 6 mg: 3 monthly intravitreal injections of brolucizumab 6 mg in the loading treatment period (q4w regimen) up to Week 8 followed by injections every 12 weeks (q12w regimen) or 8 weeks (q8w) up to Week 40 or Week 44, depending on disease activity status.
• Aflibercept 2 mg: 3 monthly intravitreal injections of aflibercept 2 mg in the loading treatment period (q4w regimen) up to Week 8 followed by injections every 8 weeks (q8w) up to Week 40. Disease activity assessments (DAAs) were conducted by the masked investigator for both treatment arms at Weeks 16, 20, 32 and 44 to determine the regimen of brolucizumab arm (i.e., q12w or q8w).

• Study Type: Interventional
• Enrollment (Actual): 397
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100730
    • Novartis Investigative Site
  • Beijing, China, 100034
    • Novartis Investigative Site
  • Beijing, China, 100050
    • Novartis Investigative Site
  • Beijing, China, 100191
    • Novartis Investigative Site
  • Chongqing, China, 400038
    • Novartis Investigative Site
  • Chongqing, China, 400042
    • Novartis Investigative Site
  • Jinan, China, 250012
    • Novartis Investigative Site
  • Shanghai, China, 200031
    • Novartis Investigative Site
  • Shanghai, China, 200080
    • Novartis Investigative Site
  • Shanghai, China, 200092
    • Novartis Investigative Site
  • Shanghai, China, 200001
    • Novartis Investigative Site
  • Beijing
    • Beijing, Beijing, China, 100044
      • Novartis Investigative Site
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Novartis Investigative Site
    • Guangzhou, Guangdong, China, 410015
      • Novartis Investigative Site
    • Shantou, Guangdong, China, 515041
      • Novartis Investigative Site
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150001
      • Novartis Investigative Site
  • Hubei
    • Wuhan, Hubei, China, 430060
      • Novartis Investigative Site
    • Wuhan, Hubei, China, 430070
      • Novartis Investigative Site
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Novartis Investigative Site
    • Nanjing City, Jiangsu, China, 210000
      • Novartis Investigative Site
    • Nantong, Jiangsu, China, 226000
      • Novartis Investigative Site
    • Yixing, Jiangsu, China, 214299
      • Novartis Investigative Site
  • Jilin
    • Changchun, Jilin, China, 130041
      • Novartis Investigative Site
  • Liaoning
    • Shenyang City, Liaoning, China, 110000
      • Novartis Investigative Site
  • Shaanxi
    • Xian, Shaanxi, China, 710004
      • Novartis Investigative Site
  • Shandong
    • Jinan, Shandong, China, 250004
      • Novartis Investigative Site
  • Shanxi
    • Taiyuan, Shanxi, China, 030002
      • Novartis Investigative Site
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Novartis Investigative Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Novartis Investigative Site
    • Hangzhou, Zhejiang, China, 310014
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Written informed consent must be obtained before any assessment was performed.
• Male or female Chinese participants ≥ 50 years of age at the time of screening.
• Active CNV lesions secondary to AMD that affect the central subfield (including retinal angiomatous proliferation lesions with a CNV component) in the study eye at screening and confirmed by the Central Reading Center (CRC).
• Total area of CNV (including both classic and occult components) must comprise > 50% of the total lesion area in the study eye at screening and confirmed by the CRC.
• Intra and/or subretinal fluid affecting the central subfield of the study eye at screening and confirmed by the CRC.
• BCVA between 78 and 23 letters, inclusive, in the study eye at screening and baseline using ETDRS testing.

Exclusion Criteria:

• Any active intraocular or periocular infection or active intraocular inflammation (e.g., infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis, uveitis) in study eye at baseline.
• Central subfield of the study eye affected by fibrosis or geographic atrophy assessed by color fundus photography at screening and confirmed by the CRC.
• Total area of fibrosis ≥ 50% of the total lesion in the study eye at screening and confirmed by the CRC.
• Subretinal blood affecting the foveal center point and/or ≥ 50% of the lesion of the study eye at screening and confirmed by the CRC.
• Previous treatment with any approved or investigational drugs for nAMD in the study eye (other than vitamin supplements).
• Retinal pigment epithelium rip/tear in the study eye at screening.
• Current vitreous hemorrhage or history of vitreous hemorrhage in the study eye within 4 weeks prior to baseline.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brolucizumab 6 mg; 3 monthly intravitreal injections of brolucizumab 6 mg in the loading treatment period (q4w regimen) up to Week 8 followed by injections every 12 weeks (q12w regimen) or 8 weeks (q8w) up to Week 40 or Week 44, depending on disease activity status.	Drug: Brolucizumab 6mg; Intravitreal injection; Other Names: Beovu
Active Comparator: Aflibercept 2 mg; 3 monthly intravitreal injections of aflibercept 2 mg in the loading treatment period (q4w regimen) up to Week 8 followed by injections every 8 weeks (q8w) up to Week 40.	Drug: Aflibercept 2 mg; Intravitreal injection; Other Names: Eylea

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline at Week 48 in Best-Corrected Visual Acuity in 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. Participants with a BCVA ETDRS letter score between 78 and 23 ETDRS letters (inclusive) at Screening and Baseline in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning. Last observation carried forward (LOCF) was used for the imputation of missing values.	Baseline, Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Change From Baseline Over the Period of Week 36 to Week 48 in Best-Corrected Visual Acuity in 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. Participants with a BCVA ETDRS letter score between 78 and 23 ETDRS letters (inclusive) at Screening and Baseline in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning. Last observation carried forward (LOCF) was used for the imputation of missing values.	Baseline, over the period Week 36 to Week 48
q12w Treatment Status at Week 48 (for Subjects Randomized to Brolucizumab 6 mg Only) - Probability	The estimate for the proportion of participants 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 for the purpose of analysis. The proportion of participants with a positive q12w treatment status was derived as follows according to the "sufficient efficacy and safety" approach: the q8w-need assessment was imputed as "Yes" at the disease activity assessment (DAA) visit following early treatment/study discontinuation due to lack of efficacy and /or lack of safety of the study treatment (applicable to both missing and non-missing DAAs).	Week 44
q12w Treatment Status at Week 48 Within the Subjects With no q8w Need During the First q12w Cycle (Week 16 and Week 20) (for Subjects Randomized to Brolucizumab 6 mg Only) - Probability	The estimate for the proportion of participants 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 for the purpose of analysis. The analysis of "q12w treatment status within the participants randomized to brolucizumab 6 mg and with no q8w need during the first q12w cycle" was based on the subset of FAS participants randomized to brolucizumab 6 mg with no identified q8w-need at Week 16 and Week 20.	Week 44
Number (%) of Participants With q8w Treatment Need as Assessed by the Investigator at First Disease Activity Assessment (DAA) Visit	For both arms, the treatment was initiated with 3 monthly injections at Weeks 0, 4 and 8 (loading phase). Week 12 was scheduled as a "no injection visit" for both arms per protocol. Therefore, by Week 16, the planned treatment exposure was identical between the treatment arms, allowing a matched comparison of brolucizumab and aflibercept up to 8 weeks after loading.	Week 16
Change From Baseline at Each Study Visit in Best-Corrected Visual Acuity in 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. Participants with a BCVA ETDRS letter score between 78 and 23 ETDRS letters (inclusive) at Screening and Baseline in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning. Last observation carried forward (LOCF) was used for the imputation of missing values.	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44
Average Change From Baseline in Best Corrected Visual Acuity (Letters Read) From Week 4 or Week 12 up to Week 48 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. Participants with a BCVA ETDRS letter score between 78 and 23 ETDRS letters (inclusive) at Screening and Baseline in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning. Last observation carried forward (LOCF) was used for the imputation of missing values.	Baseline, over the period of Week 4 or Week 12 to Week 48
Number of Subjects With Best-Corrected Visual Acuity of 73 Letters or More at Each Visit	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 between 78 and 23 ETDRS letters (inclusive) at Screening and Baseline in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning. Last observation carried forward (LOCF) was used for the imputation of missing values.	Baseline up to Week 48
Gain in BCVA (Letters Read): Number (%) of Participants Who Gained ≥ 5, ≥ 10 and ≥ 15 Letters in Best-correct Visual Acuity From Baseline or Reached BCVA ≥ 84 Letters at Week 48 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. Participants with a BCVA ETDRS letter score between 78 and 23 ETDRS letters (inclusive) at Screening and Baseline in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning. Last observation carried forward (LOCF) was used for the imputation of missing values.	Baseline up to Week 48
Gain in BCVA (Letters Read): Number (%) of Participants Who Gained ≥ 5 Letters in Best-correct Visual Acuity From Baseline or Reached BCVA >=84 Letters at the 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. Participants with a BCVA ETDRS letter score between 78 and 23 ETDRS letters (inclusive) at Screening and Baseline in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning. Last observation carried forward (LOCF) was used for the imputation of missing values.	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
Gain in BCVA (Letters Read): Number (%) of Participants Who Gained ≥ 10 Letters in Best-correct Visual Acuity From Baseline or Reached BCVA >=84 Letters at the 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. Participants with a BCVA ETDRS letter score between 78 and 23 ETDRS letters (inclusive) at Screening and Baseline in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning. Last observation carried forward (LOCF) was used for the imputation of missing values.	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
Gain in BCVA (Letters Read): Number (%) of Participants Who Gained ≥ 15 Letters in Best-correct Visual Acuity From Baseline or Reached BCVA >=84 Letters at the 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. Participants with a BCVA ETDRS letter score between 78 and 23 ETDRS letters (inclusive) at Screening and Baseline in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning. Last observation carried forward (LOCF) was used for the imputation of missing values.	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
Loss in BCVA (Letters Read): Number (%) of Participants Who Lost ≥ 5, ≥ 10 and ≥ 15 Letters in Best-correct Visual Acuity From Baseline at Week 48 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. Participants with a BCVA ETDRS letter score between 78 and 23 ETDRS letters (inclusive) at Screening and Baseline in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning. Last observation carried forward (LOCF) was used for the imputation of missing values.	Baseline, Week 48
Loss in BCVA (Letters Read): Number (%) of Participants Who Lost ≥ 5 Letters in Best-correct Visual Acuity From Baseline to Each Post-baseline Visit for the Study	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 between 78 and 23 ETDRS letters (inclusive) at Screening and Baseline in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning. Last observation carried forward (LOCF) was used for the imputation of missing values.	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
Loss in BCVA (Letters Read): Number (%) of Participants Who Lost ≥ 10 Letters in Best-correct Visual Acuity From Baseline to Each Post-baseline Visit for the Study	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 between 78 and 23 ETDRS letters (inclusive) at Screening and Baseline in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning. Last observation carried forward (LOCF) was used for the imputation of missing values.	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
Loss in BCVA (Letters Read): Number (%) of Participants Who Lost ≥ 15 Letters in Best-correct Visual Acuity From Baseline to Each Post-baseline Visit for the Study	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 between 78 and 23 ETDRS letters (inclusive) at Screening and Baseline in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better functioning. Last observation carried forward (LOCF) was used for the imputation of missing values.	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
Average Change From Baseline Over the Period Week 4 Through Week 48 in Central Subfield Thickness - Total in Study Eye	Central Subfield Thickness Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center. Central subfield thickness (CSFT) is a key anatomical parameter of central macula and is the average thickness in the center subfield as measured from the Internal Limiting Membrane (ILM) to the Bruch's Membrane (BM). The center subfield is the circular region centered on the anatomic fovea with the radius of 500 μm.	Baseline, over the period Week 4 through Week 48
Average Change From Baseline Over the Period Week 36 Through 48 in Central Subfield Thickness - Total in Study Eye	Central Subfield Thickness Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center. Central subfield thickness (CSFT) is a key anatomical parameter of central macula and is the average thickness in the center subfield as measured from the Internal Limiting Membrane (ILM) to the Bruch's Membrane (BM). The center subfield is the circular region centered on the anatomic fovea with the radius of 500 μm.	Baseline, over the period Week 36 to Week 48
Change From Baseline at Each Study Visit in Central Subfield Thickness - Total in Study Eye	Central Subfield Thickness Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center. Central subfield thickness (CSFT) is a key anatomical parameter of central macula and is the average thickness in the center subfield as measured from the Internal Limiting Membrane (ILM) to the Bruch's Membrane (BM). The center subfield is the circular region centered on the anatomic fovea with the radius of 500 μm.	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
Change From Baseline at Each Study Visit in Central Subfield Thickness - Neurosensory Retina (μm) in Study Eye	Central Subfield Thickness Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center. The central subfield thickness-neurosensory retina (CSFTns) is the average thickness in the center subfield as measured from the Internal Limiting Membrane (ILM) to the outer segment tips. The center subfield is the circular region centered on the anatomic fovea with the radius of 500μm.	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
Number of Participants With Presence of Subretinal Field (SRF) and/or Intraretinal Fluid (Central Subfield) (IRF) in the Study Eye at Each Postbaseline Visit (and Specifically Week 16 and Week 48)		Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
Number of Participants With Absence of Subretinal Field (SRF) and Intraretinal Fluid (Central Subfield) (IRF) in the Study Eye Between Week 36 and Week 48		Between Weeks 36 and Weeks 48
Subretinal Fluid (SRF) Status in the Central Subfield: Number of Subjects With Presence of SRF by Visit for the Study Eye		Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
Intraretinal Fluid (IRF) Status in the Central Subfield: Number of Subjects With Presence of IRF by Visit for the Study Eye		Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
Subretinal Pigment Epithelium (Sub-RPE) Fluid Status in the Central Subfield: Number of Subjects With Presence of Sub-RPE by Visit for the Study Eye		Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
Change From Baseline at Weeks 12 and 48 in Choroidal Neovascularization (CNV) Lesion in Study Eye		Baseline, Week 12 and Week 48
Number of Subjects With Presence of Fibrosis (Central Subfield) in the Study Eye by Visit	As assessed by color fundus photography.	Baseline, Week 12, Week 48
Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Composite Score	The VFQ-25 includes a series of 25 questions pertaining to vision or feelings about a vision condition. Answers are selected among a numbered list of possible responses, the values of which are ultimately recoded and converted to a 0 to 100 scale. Items within each subscale are averaged together to create 12 subscale scores. An overall composite score was calculated by averaging vision-targeted subscale scores, excluding the general health rating question. All items are scored so that a high score represents better visual functioning.	Baseline, Week 24 and Week 48
Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - General Vision	The VFQ-25 includes a series of 25 questions pertaining to vision or feelings about a vision condition. Answers are selected among a numbered list of possible responses, the values of which are ultimately recoded and converted to a 0 to 100 scale. Items within each subscale are averaged together to create 12 subscale scores. An overall composite score was calculated by averaging vision-targeted subscale scores, excluding the general health rating question. All items are scored so that a high score represents better visual functioning.	Baseline, Week 24 and Week 48
Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Ocular Pain	The VFQ-25 includes a series of 25 questions pertaining to vision or feelings about a vision condition. Answers are selected among a numbered list of possible responses, the values of which are ultimately recoded and converted to a 0 to 100 scale. Items within each subscale are averaged together to create 12 subscale scores. An overall composite score was calculated by averaging vision-targeted subscale scores, excluding the general health rating question. All items are scored so that a high score represents better visual functioning.	Baseline, Week 24 and Week 48
Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Near Activities	The VFQ-25 includes a series of 25 questions pertaining to vision or feelings about a vision condition. Answers are selected among a numbered list of possible responses, the values of which are ultimately recoded and converted to a 0 to 100 scale. Items within each subscale are averaged together to create 12 subscale scores. An overall composite score was calculated by averaging vision-targeted subscale scores, excluding the general health rating question. All items are scored so that a high score represents better visual functioning.	Baseline, Week 24 and Week 48
Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Distance Activities	The VFQ-25 includes a series of 25 questions pertaining to vision or feelings about a vision condition. Answers are selected among a numbered list of possible responses, the values of which are ultimately recoded and converted to a 0 to 100 scale. Items within each subscale are averaged together to create 12 subscale scores. An overall composite score was calculated by averaging vision-targeted subscale scores, excluding the general health rating question. All items are scored so that a high score represents better visual functioning.	Baseline, Week 24 and Week 48
Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Social Functioning	The VFQ-25 includes a series of 25 questions pertaining to vision or feelings about a vision condition. Answers are selected among a numbered list of possible responses, the values of which are ultimately recoded and converted to a 0 to 100 scale. Items within each subscale are averaged together to create 12 subscale scores. An overall composite score was calculated by averaging vision-targeted subscale scores, excluding the general health rating question. All items are scored so that a high score represents better visual functioning.	Baseline, Week 24 and Week 48
Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Mental Health	The VFQ-25 includes a series of 25 questions pertaining to vision or feelings about a vision condition. Answers are selected among a numbered list of possible responses, the values of which are ultimately recoded and converted to a 0 to 100 scale. Items within each subscale are averaged together to create 12 subscale scores. An overall composite score was calculated by averaging vision-targeted subscale scores, excluding the general health rating question. All items are scored so that a high score represents better visual functioning.	Baseline, Week 24 and Week 48
Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Role Difficulties	The VFQ-25 includes a series of 25 questions pertaining to vision or feelings about a vision condition. Answers are selected among a numbered list of possible responses, the values of which are ultimately recoded and converted to a 0 to 100 scale. Items within each subscale are averaged together to create 12 subscale scores. An overall composite score was calculated by averaging vision-targeted subscale scores, excluding the general health rating question. All items are scored so that a high score represents better visual functioning.	Baseline, Week 24 and Week 48
Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Dependency	The VFQ-25 includes a series of 25 questions pertaining to vision or feelings about a vision condition. Answers are selected among a numbered list of possible responses, the values of which are ultimately recoded and converted to a 0 to 100 scale. Items within each subscale are averaged together to create 12 subscale scores. An overall composite score was calculated by averaging vision-targeted subscale scores, excluding the general health rating question. All items are scored so that a high score represents better visual functioning.	Baseline, Week 24 and Week 48
Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Driving	The VFQ-25 includes a series of 25 questions pertaining to vision or feelings about a vision condition. Answers are selected among a numbered list of possible responses, the values of which are ultimately recoded and converted to a 0 to 100 scale. Items within each subscale are averaged together to create 12 subscale scores. An overall composite score was calculated by averaging vision-targeted subscale scores, excluding the general health rating question. All items are scored so that a high score represents better visual functioning.	Baseline, Week 24 and Week 48
Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Color Vision	The VFQ-25 includes a series of 25 questions pertaining to vision or feelings about a vision condition. Answers are selected among a numbered list of possible responses, the values of which are ultimately recoded and converted to a 0 to 100 scale. Items within each subscale are averaged together to create 12 subscale scores. An overall composite score was calculated by averaging vision-targeted subscale scores, excluding the general health rating question. All items are scored so that a high score represents better visual functioning.	Baseline, Week 24 and Week 48
Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Peripheral Vision	The VFQ-25 includes a series of 25 questions pertaining to vision or feelings about a vision condition. Answers are selected among a numbered list of possible responses, the values of which are ultimately recoded and converted to a 0 to 100 scale. Items within each subscale are averaged together to create 12 subscale scores. An overall composite score was calculated by averaging vision-targeted subscale scores, excluding the general health rating question. All items are scored so that a high score represents better visual functioning.	Baseline, Week 24 and Week 48
Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - General Health Rating	The VFQ-25 includes a series of 25 questions pertaining to vision or feelings about a vision condition. Answers are selected among a numbered list of possible responses, the values of which are ultimately recoded and converted to a 0 to 100 scale. Items within each subscale are averaged together to create 12 subscale scores. An overall composite score was calculated by averaging vision-targeted subscale scores, excluding the general health rating question. All items are scored so that a high score represents better visual functioning.	Baseline, Week 24 and Week 48
Anti-drug Antibody (ADA): Frequency Distribution of Pre-dose ADA Status in the Brolucizumab Arm	To assess immunogenicity of brolucizumab 6 mg.	Baseline
Anti-drug Antibody (ADA): Frequency Distribution of Integrated ADA Status in the Brolucizumab Arm	To assess immunogenicity of brolucizumab 6 mg.	Baseline up to Week 48 (End of Study)
Pharmacokinetic Parameters: Cmax After First Brolucizumab 6 mg Dose in a Subset of Subjects	The maximum (peak) observed serum drug concentration after single dose administration (mass x volume-1)	Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29
Pharmacokinetic Parameters: Tmax After First Brolucizumab 6 mg Dose in a Subset of Subjects	The time to reach maximum (peak) serum drug concentration after single dose administration (time). Actual sampling times were taken into consideration for the pharmacokinetic (PK) analysis.	Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29
Pharmacokinetic Parameters: AUClast After First Brolucizumab 6 mg Dose in a Subset of Subjects	The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1)	Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29
Pharmacokinetic Parameters: AUCinf After First Brolucizumab 6 mg Dose in a Subset of Subjects	The AUC from time zero to infinity (mass x time x volume-1)	Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29
Pharmacokinetic Parameters: T1/2 After First Brolucizumab 6 mg Dose in a Subset of Subjects	The elimination half-life associated with the terminal slope (lz) of a semi logarithmic concentration time curve (time).	Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29
Pharmacokinetic Parameters: CL/F After First Brolucizumab 6 mg Dose in a Subset of Subjects	Apparent total body clearance of siremadlin from serum (CL/F)	Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29
Pharmacokinetic Parameters: Vz/F After First Brolucizumab 6 mg Dose in a Subset of Subjects	Apparent volume of distribution during terminal elimination phase (Vz/F)	Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29
Most Common Ocular Adverse Events (Greater Than or Equal to 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. Treatment-emergent AEs are presented, which are AEs that developed on or after first study treatment administration, or any event previously present that worsened following exposure to the study treatment.	Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of approximately 48 weeks
Non-ocular Adverse Events (Greater Than or Equal to 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. Treatment-emergent AEs are counted, which are AEs that developed on or after first study treatment administration, or any event previously present that worsened following exposure to the study treatment.	Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of approximately 48 weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2019
• Primary Completion (Actual): February 28, 2024
• Study Completion (Actual): February 28, 2024

Study Registration Dates

• First Submitted: July 1, 2019
• First Submitted That Met QC Criteria: August 5, 2019
• First Posted (Actual): August 6, 2019

Study Record Updates

• Last Update Posted (Actual): December 9, 2024
• Last Update Submitted That Met QC Criteria: October 18, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: AMD; Macular degeneration; vision loss; age-related macular degeneration (AMD); wet macular degeneration; macula damage; retina damage
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Diseases; Retinal Degeneration; Macular Degeneration; Wet Macular Degeneration; Antineoplastic Agents; Physiological Effects of Drugs; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept
• Other Study ID Numbers: CRTH258A2307

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