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

Overview

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

Full Title of Study: “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

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: February 28, 2024

Interventions

  • 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.
  • Drug: Aflibercept 2 mg
    • Subjects will receive Aflibercept 3 x q4w up to Week 8 followed by q8w up to Week 40.

Arms, Groups and Cohorts

  • Experimental: Brolucizumab 6 mg
  • Active Comparator: Aflibercept 2 mg

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

  • Average change in Best-Corrected Visual Acuity
    • Time Frame: Baseline, over the period Week 36 to Week 48
    • To demonstrate that brolucizumab 6 mg is not inferior to aflibercept 2 mg with respect to the change in BCVA
  • Proportion of subjects with treatment regimen of every 12 weeks in brolucizumab arm
    • Time Frame: Baseline up to Week 48
    • To estimate the proportion of q12w subjects (1 injection every 12 weeks) up to Week 48 in the brolucizumab 6 mg treatment arm”
  • 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
    • Time Frame: Week 16, Week 20 and Week 48
    • 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
  • Change in Best Corrected Visual Acuity (BCVA)
    • Time Frame: Baseline up to Week 48
    • To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period
  • Average change in Best-Corrected Visual Acuity
    • Time Frame: Baseline, over the period of Week 4 to Week 48
    • To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period
  • Average change in Best-Corrected Visual Acuity
    • Time Frame: Baseline, over the period of Week 12 to Week 48
    • To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period
  • Proportion of patients who gain in best-correct visual acuity of 15/10/5 letters or more
    • Time Frame: Baseline up to Week 48
    • To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period
  • Percentage of subjects with Best-Corrected Visual Acuity of 73 letters or more at each visit
    • Time Frame: Baseline up to Week 48
    • To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period
  • Proportion of subjects who loss in best-corrected visual acuity of 15/10/5 letters or more
    • Time Frame: Baseline up to Week 48
    • To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period
  • Change in Central Subfield Thickness Total
    • Time Frame: Baseline up to Week 48
    • To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters
  • Average change in Central Subfield Thickness Total
    • Time Frame: Baseline, over the period of Week 36 to Week 48
    • To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters
  • Average Change in Central Subfield Thickness Total
    • Time Frame: Baseline, over the period of Week 4 to Week 48
    • To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters
  • Change in Central Subfield Thickness-neurosensory retina
    • Time Frame: From Baseline up to Week 48
    • To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters
  • Change in in area of choroidal neovascularization lesion
    • Time Frame: Baseline, Weeks 12 and Week 48
    • To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters
  • Proportion of subjects who have presence of subretinal and/or intraretinal fluid (central subfield)
    • Time Frame: Baseline up to Week 48, specifically at Week 16 and Week 48
    • To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters
  • Number of visits with simultaneous absence of subretinal and intraretinal fluid (central subfield)
    • Time Frame: Over the period of Week 36 to Week 48
    • To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters
  • Proportion of subjects who have presence of subretinal fluid (central subfield)
    • Time Frame: Baseline up to Week 48
    • To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters
  • Proportion of subjects who have presence of intraretinal fluid (central subfield)
    • Time Frame: Baseline up to Week 48
    • To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters
  • Proportion of subjects who presence of sub retinal pigment epithelium fluid (central subfield)
    • Time Frame: Baseline up to Week 48
    • To evaluate the efficacy of brolucizumab 6 mg relative to aflibercept 2 mg over the time period by assessing changes in anatomical parameters
  • Change in Central Subfield Thickness Total
    • Time Frame: Baseline up to week 16
    • 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
  • Proportion of subjects who presence of subretinal and /or intraretinal fluid (central subfield)
    • Time Frame: At Week 16
    • 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
  • Proportion of subjects who need every 8 weeks injection
    • Time Frame: At Week 16
    • 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
  • Change in subject reported outcomes (Visual Function Questionnaire-25) total and subscale scores
    • Time Frame: Baseline up to Weeks 24 and Week 48
    • 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.
  • Proportion of subjects who have positive anti-drug antibodies status
    • Time Frame: At Baseline (enrollment), Weeks 4, 12, 24, 36, and 48 (End of Study)
    • To assess immunogenicity of brolucizumab 6 mg
  • Pharmacokinetic parameters: Cmax after first brolucizumab 6 mg dose in a subset of subjects
    • Time Frame: Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29
    • 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
  • Pharmacokinetic parameters: Tmax after first brolucizumab 6 mg dose in a subset of subjects
    • Time Frame: Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29
    • 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
  • Pharmacokinetic parameters: AUClast after first brolucizumab 6 mg dose in a subset of subjects
    • Time Frame: Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29
    • 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
  • Pharmacokinetic parameters: AUCinf after first brolucizumab 6 mg dose in a subset of subjects
    • Time Frame: Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29
    • 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
  • Pharmacokinetic parameters: Thalf after first brolucizumab 6 mg dose in a subset of subjects
    • Time Frame: Day 1, Day 2, Day 8, Day 15, Day 22, and Day 29
    • 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

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 50 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Novartis Pharmaceuticals
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Novartis Pharmaceuticals, Study Director, Novartis Pharmaceuticals

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