Efficacy and Safety of Brolucizumab vs. Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema (BUZZARD)

A Comparative Double Masked, Two-Arm, Randomized, Multicenter, Phase IIIb Study Analyzing the Efficacy and Safety of Brolucizumab Versus Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema (BUZZARD)

The purpose of this study is to evaluate the efficacy and safety of brolucizumab in treatment of patients with visual impairment due to diabetic macular edema (DME).

Study Overview

• Status: Withdrawn
• Conditions: Diabetic Macula Edema
• Intervention / Treatment: Drug: Aflibercept; Drug: Brolucizumab

Detailed Description

In this 48-week, randomized, double-masked, multicenter, active controlled study, consenting patients will be randomized in a 1:1 ratio to one of the two treatment arms and attend 14 planned visits.

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 110 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with type 1 or type 2 diabetes mellitus and HbA1c of ≤10% at Screening
• BCVA score between 23 and 65 letters, inclusive, using ETDRS visual acuity testing charts at a testing distance of 4 meters (approximate Snellen equivalent of 20/50 to 20/320), at screening and baseline
• DME involving the center of the macula, with central subfield retinal thickness (measured from RPE to ILM inclusively) of ≥ 320 µm on SD-OCT

Exclusion Criteria:

• High risk or advanced proliferative diabetic retinopathy in the study eye as per reading Center
• Active intraocular or periocular infection or active intraocular inflammation in the study eye
• Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) > 25 millimeters mercury (mmHg)
• Previous treatment with any anti-VEGF drugs or investigational drugs in the study eye in the last 3 months prior randomization
• Stroke or myocardial infarction during the 6-month period prior to baseline
• Uncontrolled blood pressure defined as a systolic value ≥160 mmHg or diastolic value ≥100 mmHg Other protocol-specified inclusion/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; Brolucizumab 6 mg/0.05 mL, 5 loading doses, with subsequent doses per protocol-specified maintenance schedule	Drug: Brolucizumab; Intravitreal Injection; Other Names: RTH258, ESBA1008
Active Comparator: Aflibercept 2 mg; Aflibercept 2 mg/0.05 mL, as labeled, 5 loading doses, with subsequent doses every 8 weeks	Drug: Aflibercept; Intravitreal injection; Other Names: Eylea

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with a gain in Best Corrected Visual Acurity (BCVA) of ≥15 ETDRS letters at week 48	BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts	Week 48
Mean change in BCVA from baseline to Week 48	BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts	Baseline, Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in BCVA averaged over a period Week 36 to Week 48	BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts	Week 36, Week 48
Proportion of patients with a gain in BCVA of ≥10 ETDRS letters from baseline to Week 48	BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts	Baseline, Week 48
Proportion of patients with a loss in BCVA of ≥15 ETDRS letters from baseline to Week 48	BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts	Baseline, Week 48
Proportion of patients with a loss in BCVA of ≥10 ETDRS letters from baseline to Week 48	BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts	Baseline, Week 48
Proportion of patients maintained at q12w up to Week 48	Percentage of participants maintained at q12w (quarterly, every 12 weeks). This outcome measure is pre-specified for brolucizumab treatment arm only	Baseline, Week 48
Proportion of patients maintained at q12w up to Week 48, within those patients that qualified for q12w at week 28	Percentage of patients maintained at (q12w) quarterly, every 12 weeks, up to Week 48, within those patients that qualified for (q12w) at week 28. This outcome measure is pre-specified for brolucizumab treatment arm only	Week 28, Week 48
Change from baseline in central subfield thickness (CSFT, as determined by SD-OCT) at each assessment visit	Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)	Baseline, Week 48
Average change in CSFT from baseline over the period Week 36 through Week 48	Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)	Week 36, Week 48
Average change in CSFT from baseline over the period Week 4 to Week 48	Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)	Week 4, Week 48
Patient status regarding normal CSFT thickness (<280 microns) at each assessment visit	Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)	Baseline, Week 48
Change from baseline in Central Subfield Thickness-neurosensory (CSFTns, as determined by SD-OCT) at each assessment visit	Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)	Baseline, week 48
Average change in CSFTns from baseline over the period Week 36 through Week 48	Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)	Baseline, Week 36, Week 48
Average change in CSFTns from baseline over the period Week 4 to Week 48	Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)	Baseline, Week 4, Week 48
Proportion of patients with presence of SRF, IRF and simultaneous absence of SRF and IRF at each assessment visit	Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)	Baseline, Week 48
Proportion of patients with presence of leakage on FA at Week 48	Assessed by fluorescein angiography	Week 48
Change in ETDRS Diabetic Retinopathy Severity Scale (DRSS) score up to Week 48 (central reading)	The Diabetic Retinopathy Disease Severity Scale measures the 5 levels of diabetic retinopathy - none, mild, moderate, severe, and proliferative	Baseline, Week 48
Patient status regarding a ≥2- and ≥3-step improvement or worsening from baseline in the ETDRS Diabetic Retinopathy Severity Scale (DRSS) score at each assessment visit	Disease status measured by ETDRS-DRSS. Diabetic Retinopathy Severity Scale (DRSS) score at each assessment visit.	Baseline, Week 48
Incidence of progression to PDR as assessed by ETDRS-DRSS score of at least 61 by Week 48	Incidence of progression to proliferative diabetic retinopathy (PDR) measured by ETDRS-DRSS. Diabetic Retinopathy Severity Scale (DRSS) score at each assessment visit.	Baseline, Week 48
Rate of "inactive" PDRs by Week 48 compared to baseline	Rate of "inactive" proliferative diabetic retinopathy (PDRs) by Week 48 compared to baseline as measured by Diabetic Retinopathy Severity Scale (DRSS) score.	Baseline, Week 48

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2021
• Primary Completion (Anticipated): January 31, 2023
• Study Completion (Anticipated): January 31, 2023

Study Registration Dates

• First Submitted: August 12, 2019
• First Submitted That Met QC Criteria: September 4, 2019
• First Posted (Actual): September 6, 2019

Study Record Updates

• Last Update Posted (Actual): March 4, 2021
• Last Update Submitted That Met QC Criteria: March 2, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: aflibercept; Intravitreal injection; Diabetic Macula Edema; brolucizumab; double-masked
• Additional Relevant MeSH Terms: Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Sensation Disorders; Macular Edema; Edema; Vision, Low; Vision Disorders; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept
• Other Study ID Numbers: CRTH258BDE01

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 ww.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