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

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

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: +41613241111; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals

Study Locations

• China
  • Beijing, China, 100044
    • Novartis Investigative Site
  • 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
  • Nanjing, China, 210036
    • 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
  • 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 City, Jiangsu, China, 210000
      • Novartis Investigative Site
    • Nantong, Jiangsu, China, 226000
      • Novartis Investigative Site
    • Yixing, Jiangsu, China, 214299
      • Novartis Investigative Site
  • Jilin
    • Changchun City, 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
    • Tianjin, Tianjin, China, 300070
      • 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 is performed.
• Active choroidal neovascularization (CNV) lesions secondary to AMD that affect the central subfield in the study eye
• Total area of CNV>50% of the total lesion area in the study eye at screening

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
• Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) >25 mmHg
• Previous treatment with any anti-VEGF drugs in the study eye.
• Previous treatment with any approved or investigational drugs for neovascular AMD in the study eye.

Other protocol-specified inclusion or exclusion criteria may apply.

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	Drug: Brolucizumab 6mg; Subjects will receive Brolucizumab 3 x q4w up to Week 8 followed by q12w / q8w up to Week 40 or Week 44, depending on disease activity status.
Active Comparator: Aflibercept 2 mg	Drug: Aflibercept 2 mg; Subjects will receive Aflibercept 3 x q4w up to Week 8 followed by q8w up to Week 40.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Best-Corrected Visual Acuity	To demonstrate that brolucizumab 6 mg is not inferior to aflibercept 2 mg with respect to the change in BCVA	Baseline to Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average change in Best-Corrected Visual Acuity	To demonstrate that brolucizumab 6 mg is not inferior to aflibercept 2 mg with respect to the change in BCVA	Baseline, over the period Week 36 to Week 48
Proportion of subjects with treatment regimen of every 12 weeks in brolucizumab arm	To estimate the proportion of q12w subjects (1 injection every 12 weeks) up to Week 48 in the brolucizumab 6 mg treatment arm"	Baseline up to Week 48
Proportion of patients with treatment regimen of every 12 weeks (q12w) interval at Week 48 of those who do not need every 8 weeks treatment interval in brolucizumab arm	To estimate the predictive value of the first regimen of every 12 weeks (q12w) cycle (at Week 16 and Week 20) for maintenance of q12w treatment regimen	Week 16, Week 20 and Week 48
Change in Best Corrected Visual Acuity (BCVA)	To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period	Baseline up to Week 48
Average change in Best-Corrected Visual Acuity	To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period	Baseline, over the period of Week 4 to Week 48
Average change in Best-Corrected Visual Acuity	To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period	Baseline, over the period of Week 12 to Week 48
Proportion of patients who gain in best-correct visual acuity of 15/10/5 letters or more	To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period	Baseline up to Week 48
Percentage of subjects with Best-Corrected Visual Acuity of 73 letters or more at each visit	To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period	Baseline up to Week 48
Proportion of subjects who loss in best-corrected visual acuity of 15/10/5 letters or more	To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period	Baseline up to Week 48
Change in Central Subfield Thickness Total	To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters	Baseline up to Week 48
Average change in Central Subfield Thickness Total	To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters	Baseline, over the period of Week 36 to Week 48
Average Change in Central Subfield Thickness Total	To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters	Baseline, over the period of Week 4 to Week 48
Change in Central Subfield Thickness-neurosensory retina	To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters	From Baseline up to Week 48
Change in in area of choroidal neovascularization lesion	To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters	Baseline, Weeks 12 and Week 48
Proportion of subjects who have presence of subretinal and/or intraretinal fluid (central subfield)	To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters	Baseline up to Week 48, specifically at Week 16 and Week 48
Number of visits with simultaneous absence of subretinal and intraretinal fluid (central subfield)	To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters	Over the period of Week 36 to Week 48
Proportion of subjects who have presence of subretinal fluid (central subfield)	To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters	Baseline up to Week 48
Proportion of subjects who have presence of intraretinal fluid (central subfield)	To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters	Baseline up to Week 48
Proportion of subjects who presence of sub retinal pigment epithelium fluid (central subfield)	To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters	Baseline up to Week 48
Change in Central Subfield Thickness Total	To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg at the end of the matched treatment phase	Baseline up to week 16
Proportion of subjects who presence of subretinal and /or intraretinal fluid (central subfield)	To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg at the end of the matched treatment phase	At Week 16
Proportion of subjects who need every 8 weeks injection	To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg at the end of the matched treatment phase	At Week 16
Change in subject reported outcomes (Visual Function Questionnaire-25) total and subscale scores	To assess visual function-related subject reported outcomes following treatment with brolucizumab 6 mg relative to aflibercept 2 mg. 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 will be calculated by averaging vision-targeted subscale scores, excluding the general health rating question.	Baseline up to Weeks 24 and Week 48
Proportion of subjects who have positive anti-drug antibodies status	To assess immunogenicity of brolucizumab 6 mg	At Baseline (enrollment), Weeks 4, 12, 24, 36, and 48 (End of Study)
Pharmacokinetic parameters: Cmax after first brolucizumab 6 mg dose in a subset of subjects	PK draw 6 hours post-injection on Day 1, after first brolucizumab 6 mg dose in a subset of subjects to assess Cmax (maximum concentration) of brolucizumab at 6 mg following a single intravitreal injection	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	PK draw 6 hours post-injection on Day 1, after first brolucizumab 6 mg dose in a subset of subjects to assess Tmax (time to maximum concenration) of brolucizumab at 6 mg following a single intravitreal injection	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	PK draw 6 hours post-injection on Day 1, after first brolucizumab 6 mg dose in a subset of subjects to assess AUClast (Area under the curve up to the last validated measurable plasma concentration) of brolucizumab at 6 mg following a single intravitreal injection	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	PK draw 6 hours post-injection on Day 1, after first brolucizumab 6 mg dose in a subset of subjects to assess AUCinf (area under the curve total exposure) of brolucizumab at 6 mg following a single intravitreal injection	Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29
Pharmacokinetic parameters: Thalf after first brolucizumab 6 mg dose in a subset of subjects	PK draw 6 hours post-injection on Day 1, after first brolucizumab 6 mg dose in a subset of subjects to assess Thalf (time to elimination of half-life) of brolucizumab at 6 mg following a single intravitreal injection	Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29

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): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Wet Macular Degeneration; Physiological Effects of Drugs; Antineoplastic Agents; 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