To compare brolucizumab to aflibercept in Chinese patients with untreated active choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD)
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
397
Intravitreal injection
Intravitreal injection
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.
Time frame: Baseline, Week 48
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.
Time frame: 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).
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Novartis Investigative Site
Beijing, Beijing Municipality, China
Novartis Investigative Site
Guangzhou, Guangdong, China
Novartis Investigative Site
Guangzhou, Guangdong, China
Novartis Investigative Site
Shantou, Guangdong, China
Novartis Investigative Site
Harbin, Heilongjiang, China
Novartis Investigative Site
Wuhan, Hubei, China
Novartis Investigative Site
Wuhan, Hubei, China
Novartis Investigative Site
Nanjing, Jiangsu, China
Novartis Investigative Site
Nanjing, Jiangsu, China
Novartis Investigative Site
Nantong, Jiangsu, China
...and 20 more locations
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline
Anti-drug Antibody (ADA): Frequency Distribution of Integrated ADA Status in the Brolucizumab Arm
To assess immunogenicity of brolucizumab 6 mg.
Time frame: 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)
Time frame: 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.
Time frame: 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)
Time frame: 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)
Time frame: 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).
Time frame: 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)
Time frame: 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)
Time frame: 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.
Time frame: 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.
Time frame: 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