A Study of the Efficacy and Safety of Brolucizumab vs. Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema

• Register: ClinicalTrials.gov
• Last refreshed on: 11 March 2024
• Main ID: NCT03481660
• Date of registration: 19/03/2018
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharmaceuticals
• Public title: A Study of the Efficacy and Safety of Brolucizumab vs. Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema KITE
• Scientific title: A Two-Year, Two-Arm, Randomized, Double Masked, Multicenter, Phase III Study Assessing the Efficacy and Safety of Brolucizumab Versus Aflibercept in Adult Patients With Visual Impairment Due to Diabetic Macular Edema
• Date of first enrolment: July 27, 2018
• Target sample size: 360
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT03481660
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Belgium, Bulgaria, Czechia, Denmark, Estonia, France, Germany, Hungary, India, Korea, Republic of, Latvia, Lebanon, Lithuania, Malaysia, Norway, Poland, Russian Federation, Singapore, Slovakia, Sweden, Switzerland, Taiwan, Turkey

Contacts

• Name: Novartis Pharmaceuticals
• Affiliation: Novartis Pharmaceuticals

Key inclusion & exclusion criteria

Key Inclusion Criteria:

General

- Patients must give written informed consent before any study related assessments are
performed

- Patients with type 1 or type 2 diabetes mellitus and HbA1c of =< 10% at screening

- Medication for the management of diabetes must have been stable within 3 months prior
to randomization and is expected to remain stable during the course of the study

Study Eye

- Visual impairment due to DME with:

1. BCVA score between 78 and 23 letters, inclusive, using Early Treatment Diabetic
Retinopathy Study (ETDRS) visual acuity testing charts at a testing distance of 4
meters (approximate Snellen equivalent of 20/32 to 20/320), at screening and
baseline

2. DME involving the center of the macula, with central subfield retinal thickness
(measured from RPE to ILM inclusively) of >= 320 micrometers (µm) on SD-OCT at
screening If both eyes are eligible, the eye with the worse visual acuity will be
selected for study eye. However, the investigator may select the eye with better
visual acuity, based on medical reasons or local ethical requirements.

Key Exclusion Criteria:

- Previous treatment with any anti-VEGF drugs or investigational drugs in the study eye

- Active proliferative diabetic retinopathy in the study eye as per the investigator

- Concomitant conditions or ocular disorders in the study eye at screening or baseline
which could, in the opinion of the investigator, prevent response to study treatment
or may confound interpretation of study results, compromise visual acuity or require
medical or surgical intervention during the first 12-month study period (e.g.,
cataract, vitreous hemorrhage, retinal vascular occlusion, retinal detachment, macular
hole, or choroidal neovascularization of any cause)

- Any active intraocular or periocular infection or active intraocular inflammation
(e.g., infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious
blepharitis, uveitis) in study eye at screening or baseline

- Structural damage of the fovea in the study eye at screening likely to preclude
improvement in visual acuity following the resolution of macular edema, including
atrophy of the retinal pigment epithelium, subretinal fibrosis, laser scar(s),
epiretinal membrane involving fovea or organized hard exudate plaques

- Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) > 25
millimeters mercury (mmHg) on medication or according to investigator's judgment, at
screening or baseline

- Neovascularization of the iris in the study eye at screening or baseline

- Evidence of vitreomacular traction in the study eye at screening or baseline which, in
the opinion of the investigator, affect visual acuity



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Diabetic Macular Edema

Intervention(s)

Drug: Brolucizumab

Drug: Aflibercept

Primary Outcome(s)

Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) at Week 52 for the Study Eye [Time Frame: Baseline, Week 52]

Secondary Outcome(s)

Average Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Over the Period Week 88 to 100 for the Study Eye [Time Frame: Baseline, period Week 88 through Week 100]

Distribution of Integrated Anti-Drug Antibody (ADA) Status in the Brolucizumab Arm - Adjusted for Pre-existing ADA Status [Time Frame: Up to Week 100]

Percentage of Participants Who Lost >= 15 ETDRS Letters in Best Corrected Visual Acuity (BCVA) From Baseline at Each Post-baseline Visit for the Study Eye [Time Frame: Baseline, Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100]

Percentage of Participants With With >=3-step Improvement From Baseline in ETDRS Diabetic Retinopathy Severity Scale (ETDRS-DRSS) Score [Time Frame: Baseline, Week 28, Week 52, Week 76, Week 100]

Average Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Over the Period Week 20 to Week 52/100 and Week 28 to Week 52/100 for the Study Eye [Time Frame: Baseline, period Week 20 through Week 52, period Week 20 through Week 100, period Week 28 through Week 52, period Week 28 through Week 100]

Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Mental Health [Time Frame: Baseline, Week 28, Week 52, Week 76, Week 100]

Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Social Functioning [Time Frame: Baseline, Week 28, Week 52, Week 76, Week 100]

Integrated ADA Status up to Week 100 and Incidence of Adverse Event of Special Interest (AESI) in the Study Eye. [Time Frame: Up to Week 100]

Percentage of Patients With Presence of Subretinal Fluid (SRF) in the Study Eye at Each Post-baseline Visit [Time Frame: Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100]

Average Mean Change From Baseline in BCVA Over the Period Week 40 Through Week 52 for the Study Eye [Time Frame: Baseline, period Week 40 through Week 52]

Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Peripheral Vision [Time Frame: Baseline, Week 28, Week 52, Week 76, Week 100]

Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Role Difficulties [Time Frame: Baseline, Week 28, Week 52, Week 76, Week 100]

Percentage of Participants Who Gained >= 15 Letters in BCVA From Baseline or Reached BCVA >= 84 Letters at Each Post-baseline Visit for the Study Eye [Time Frame: Baseline, Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100]

Percentage of Participants With Progression to Proliferative Diabetic Retinopathy (PDR) as Assessed by ETDRS-DRSS Score of at Least 61 by Week 100 [Time Frame: Week 100]

Percentage of Participants With With >=2-step Worsening From Baseline in ETDRS Diabetic Retinopathy Severity Scale (ETDRS-DRSS) Score [Time Frame: Baseline, Week 28, Week 52, Week 76, Week 100]

Percentage of Patients With Presence of Subretinal Fluid (SRF) and/or Intraretinal Fluid (IRF) in the Study Eye at Each Post-baseline Visit [Time Frame: Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100]

(Brolucizumab Treatment Arm Only): Percentage of Participants Maintained on q16w up to Week 100 Within the Patients on q12w at Week 68 and on q16w at Week 76 [Time Frame: Week 68, Week 76, Week 100]

Systemic Brolucizumab Concentration [Time Frame: Up to Week 24]

(Brolucizumab Treatment Arm Only): Percentage of Participants Re-assigned and Maintained on q12w up to Week 100 Within the Patients on q8w at Week 68 and on q12w at Week 80 [Time Frame: Week 68, Week 80, Week 100]

Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Composite Score [Time Frame: Baseline, Week 28, Week 52, Week 76, Week 100]

Mean Change From Baseline in Central Subfield Thickness (CSFT) at Each Post-baseline Visit for the Study Eye [Time Frame: Baseline, Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100]

Number of Participants With Ocular and Non-ocular Adverse Events (AEs) [Time Frame: From randomization till 30 days safety follow-up, assessed up to 35 months.]

Percentage of Participants Who Gained >= 5 Letters in BCVA From Baseline or Reached BCVA >= 84 Letters at Each Post-baseline Visit for the Study Eye [Time Frame: Baseline, Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100]

Percentage of Participants Who Lost >= 10 ETDRS Letters in Best Corrected Visual Acuity (BCVA) From Baseline at Each Post-baseline Visit for the Study Eye [Time Frame: Baseline, Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100]

Percentage of Participants With an Absolute Best Corrected Visual Acuity (BCVA) >= 73 ETDRS Letters at Each Post-baseline Visit for the Study Eye [Time Frame: Baseline, Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100]

Percentage of Participants With With >=2-step Improvement From Baseline in ETDRS Diabetic Retinopathy Severity Scale (ETDRS-DRSS) Score [Time Frame: Baseline, Week 28, Week 52, Week 76, Week 100]

(Brolucizumab Treatment Arm Only): Percentage of Participants Maintained at q12w up to Week 52 and up to q12w/q16w up to Week 100. [Time Frame: Week 52, Week 100]

Average Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Over the Period Week 4 to Week 52/100 for the Study Eye [Time Frame: Baseline, period Week 4 through Week 52, period Week 4 through Week 100]

Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Driving [Time Frame: Baseline, Week 28, Week 52, Week 76, Week 100]

Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Each Visit up to Week 100 for the Study Eye [Time Frame: Baseline, Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100]

Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Distance Activities [Time Frame: Baseline, Week 28, Week 52, Week 76, Week 100]

Percentage of Participants With Presence of Leakage on Fluorescein Angiography (FA) at Weeks 52 and 100 [Time Frame: Week 52, Week 100]

Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - General Vision [Time Frame: Baseline, Week 28, Week 52, Week 76, Week 100]

Percentage of Participants With With >=3-step Worsening From Baseline in ETDRS Diabetic Retinopathy Severity Scale (ETDRS-DRSS) Score [Time Frame: Baseline, Week 28, Week 52, Week 76, Week 100]

Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Near Activities [Time Frame: Baseline, Week 28, Week 52, Week 76, Week 100]

Distribution of Integrated Anti-Drug Antibody (ADA) Status in the Brolucizumab Arm [Time Frame: Up to Week 100]

Percentage of Participants With Normal CSFT Thickness (<280 Micrometers) at Each Post-baseline Visit for the Study Eye [Time Frame: Baseline, Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100]

(Brolucizumab Treatment Arm Only): Number of Participants With Injections Per Planned Dosing Regimen (Every 8, 12 or 16 Weeks) [Time Frame: Week 100]

Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): General Health Rating [Time Frame: Baseline, Week 28, Week 52, Week 76, Week 100]

Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Dependency [Time Frame: Baseline, Week 28, Week 52, Week 76, Week 100]

Percentage of Participants Who Lost >= 5 ETDRS Letters in Best Corrected Visual Acuity (BCVA) From Baseline at Each Post-baseline Visit for the Study Eye [Time Frame: Baseline, Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100]

(Brolucizumab Treatment Arm Only): Percentage of Participants Maintained at q12w up to Week 52 Within Those Patients That Qualified for q12w at Week 36 [Time Frame: Week 36, Week 52]

(Brolucizumab Treatment Arm Only): Percentage of Participants Maintained at q12w/q16w up to Week 100, Within Those Patients That Qualified for q12w at Week 36 [Time Frame: Week 36, Week 100]

Average Mean Change From Baseline in Central Subfield Thickness (CSFT) Over the Period Week 40 Through Week 52 / Week 88 Through Week 100 for the Study Eye [Time Frame: Baseline, period Week 40 through Week 52, period Week 88 through Week 100]

Average Mean Change From Baseline in CSFT Over the Period Week 4 to Week 52 / 100 for the Study Eye [Time Frame: Baseline, period Week 4 through Week 52, period Week 4 through Week 100]

Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Color Vision [Time Frame: Baseline, Week 28, Week 52, Week 76, Week 100]

Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Ocular Pain [Time Frame: Baseline, Week 28, Week 52, Week 76, Week 100]

Percentage of Participants Who Gained >= 10 Letters in BCVA From Baseline or Reached BCVA >= 84 Letters at Each Post-baseline Visit for the Study Eye [Time Frame: Baseline, Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100]

Percentage of Patients With Presence of Intraretinal Fluid (IRF) in the Study Eye at Each Post-baseline Visit [Time Frame: Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100]

Pre-existing ADA Status and Incidence of Adverse Event of Special Interest (AESI) in the Study Eye [Time Frame: Up to Week 100]

Secondary ID(s)

2017-003960-11

CRTH258B2302

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 05/01/2024
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03481660