Clinical trial NCT04047472: Study of Efficacy and Safety of Brolucizumab vs. Aflibercept in Chinese Patients With Neovascular Age-Related Macular Degeneration
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Neovascular Age-Related Macular Degeneration
Keywords: Macular degeneration
age-related macular degeneration (AMD)
vision loss
macula damage
retina damage
wet macular degeneration
AMD
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2019-08-06
Enrollment: 397
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline at Week 48 in Best-Corrected Visual Acuity in Study Eye
timeFrame: Baseline, Week 48
Secondary outcomes:
measure: Average Change From Baseline Over the Period of Week 36 to Week 48 in Best-Corrected Visual Acuity in Study Eye
timeFrame: Baseline, over the period Week 36 to Week 48
measure: q12w Treatment Status at Week 48 (for Subjects Randomized to Brolucizumab 6 mg Only) - Probability
timeFrame: Week 44
measure: 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
timeFrame: Week 44
measure: Number (%) of Participants With q8w Treatment Need as Assessed by the Investigator at First Disease Activity Assessment (DAA) Visit
timeFrame: Week 16
measure: Change From Baseline at Each Study Visit in Best-Corrected Visual Acuity in Study Eye
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44
measure: 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
timeFrame: Baseline, over the period of Week 4 or Week 12 to Week 48
measure: Number of Subjects With Best-Corrected Visual Acuity of 73 Letters or More at Each Visit
timeFrame: Baseline up to Week 48
measure: 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
timeFrame: Baseline up to Week 48
measure: 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
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
measure: 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
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
measure: 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
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
measure: 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
timeFrame: Baseline, Week 48
measure: 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
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
measure: 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
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
measure: 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
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
measure: Average Change From Baseline Over the Period Week 4 Through Week 48 in Central Subfield Thickness - Total in Study Eye
timeFrame: Baseline, over the period Week 4 through Week 48
measure: Average Change From Baseline Over the Period Week 36 Through 48 in Central Subfield Thickness - Total in Study Eye
timeFrame: Baseline, over the period Week 36 to Week 48
measure: Change From Baseline at Each Study Visit in Central Subfield Thickness - Total in Study Eye
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
measure: Change From Baseline at Each Study Visit in Central Subfield Thickness - Neurosensory Retina (μm) in Study Eye
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
measure: 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)
timeFrame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
measure: 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
timeFrame: Between Weeks 36 and Weeks 48
measure: Subretinal Fluid (SRF) Status in the Central Subfield: Number of Subjects With Presence of SRF by Visit for the Study Eye
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
measure: Intraretinal Fluid (IRF) Status in the Central Subfield: Number of Subjects With Presence of IRF by Visit for the Study Eye
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
measure: 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
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
measure: Change From Baseline at Weeks 12 and 48 in Choroidal Neovascularization (CNV) Lesion in Study Eye
timeFrame: Baseline, Week 12 and Week 48
measure: Number of Subjects With Presence of Fibrosis (Central Subfield) in the Study Eye by Visit
timeFrame: Baseline, Week 12, Week 48
measure: Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Composite Score
timeFrame: Baseline, Week 24 and Week 48
measure: Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - General Vision
timeFrame: Baseline, Week 24 and Week 48
measure: Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Ocular Pain
timeFrame: Baseline, Week 24 and Week 48
measure: Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Near Activities
timeFrame: Baseline, Week 24 and Week 48
measure: Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Distance Activities
timeFrame: Baseline, Week 24 and Week 48
measure: Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Social Functioning
timeFrame: Baseline, Week 24 and Week 48
measure: Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Mental Health
timeFrame: Baseline, Week 24 and Week 48
measure: Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Role Difficulties
timeFrame: Baseline, Week 24 and Week 48
measure: Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Dependency
timeFrame: Baseline, Week 24 and Week 48
measure: Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Driving
timeFrame: Baseline, Week 24 and Week 48
measure: Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Color Vision
timeFrame: Baseline, Week 24 and Week 48
measure: Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - Peripheral Vision
timeFrame: Baseline, Week 24 and Week 48
measure: Change in Subject Reported Outcomes (Visual Function Questionnaire-25) - General Health Rating
timeFrame: Baseline, Week 24 and Week 48
measure: Anti-drug Antibody (ADA): Frequency Distribution of Pre-dose ADA Status in the Brolucizumab Arm
timeFrame: Baseline
measure: Anti-drug Antibody (ADA): Frequency Distribution of Integrated ADA Status in the Brolucizumab Arm
timeFrame: Baseline up to Week 48 (End of Study)
measure: Pharmacokinetic Parameters: Cmax After First Brolucizumab 6 mg Dose in a Subset of Subjects
timeFrame: Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29
measure: Pharmacokinetic Parameters: Tmax After First Brolucizumab 6 mg Dose in a Subset of Subjects
timeFrame: Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29
measure: Pharmacokinetic Parameters: AUClast After First Brolucizumab 6 mg Dose in a Subset of Subjects
timeFrame: Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29
measure: Pharmacokinetic Parameters: AUCinf After First Brolucizumab 6 mg Dose in a Subset of Subjects
timeFrame: Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29
measure: Pharmacokinetic Parameters: T1/2 After First Brolucizumab 6 mg Dose in a Subset of Subjects
timeFrame: Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29
measure: Pharmacokinetic Parameters: CL/F After First Brolucizumab 6 mg Dose in a Subset of Subjects
timeFrame: Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29
measure: Pharmacokinetic Parameters: Vz/F After First Brolucizumab 6 mg Dose in a Subset of Subjects
timeFrame: Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29
measure: Most Common Ocular Adverse Events (Greater Than or Equal to 2% in Any Treatment Arm) by Preferred Term for the Study Eye
timeFrame: 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
measure: Non-ocular Adverse Events (Greater Than or Equal to 2% in Any Treatment Arm)
timeFrame: 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
Other outcomes:
Locations:
city: Beijing
country: China
facility: Novartis Investigative Site
state: Beijing
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Shantou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Harbin
country: China
facility: Novartis Investigative Site
state: Heilongjiang
city: Wuhan
country: China
facility: Novartis Investigative Site
state: Hubei
city: Wuhan
country: China
facility: Novartis Investigative Site
state: Hubei
city: Nanjing City
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Nanjing
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Nantong
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Yixing
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Changchun
country: China
facility: Novartis Investigative Site
state: Jilin
city: Shenyang City
country: China
facility: Novartis Investigative Site
state: Liaoning
city: Xian
country: China
facility: Novartis Investigative Site
state: Shaanxi
city: Jinan
country: China
facility: Novartis Investigative Site
state: Shandong
city: Taiyuan
country: China
facility: Novartis Investigative Site
state: Shanxi
city: Tianjin
country: China
facility: Novartis Investigative Site
state: Tianjin
city: Hangzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Hangzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Beijing
country: China
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Chongqing
country: China
facility: Novartis Investigative Site
city: Chongqing
country: China
facility: Novartis Investigative Site
city: Jinan
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: