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

March 2, 2021 updated by: Novartis Pharmaceuticals

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

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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
Time Frame: 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
Time Frame: Baseline, Week 48
BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts
Baseline, Week 48

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change from baseline in BCVA averaged over a period Week 36 to Week 48
Time Frame: Week 36, 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
Time Frame: Baseline, 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
Time Frame: Baseline, 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
Time Frame: Baseline, 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
Time Frame: Baseline, 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
Time Frame: Week 28, Week 48
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
Time Frame: Baseline, Week 48
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
Time Frame: Week 36, 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
Time Frame: Week 4, 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
Time Frame: Baseline, Week 48
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
Time Frame: Baseline, week 48
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
Time Frame: Baseline, Week 36, 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
Time Frame: Baseline, Week 4, 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
Time Frame: Baseline, Week 48
Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)
Baseline, Week 48
Proportion of patients with presence of leakage on FA at Week 48
Time Frame: Week 48
Assessed by fluorescein angiography
Week 48
Change in ETDRS Diabetic Retinopathy Severity Scale (DRSS) score up to Week 48 (central reading)
Time Frame: Baseline, Week 48
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
Time Frame: Baseline, Week 48
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
Time Frame: Baseline, 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
Time Frame: Baseline, Week 48
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Novartis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 31, 2023

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 31, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 12, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 4, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 6, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 4, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 2, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Conditions

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