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

Primary Purpose

Diabetic Macula Edema

Status
Withdrawn
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Brolucizumab
Aflibercept
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetic Macula Edema focused on measuring Diabetic Macula Edema, Intravitreal injection, brolucizumab, aflibercept, double-masked

Eligibility Criteria

18 Years - 110 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Brolucizumab 6 mg

    Aflibercept 2 mg

    Arm Description

    Brolucizumab 6 mg/0.05 mL, 5 loading doses, with subsequent doses per protocol-specified maintenance schedule

    Aflibercept 2 mg/0.05 mL, as labeled, 5 loading doses, with subsequent doses every 8 weeks

    Outcomes

    Primary Outcome Measures

    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
    Mean change in BCVA from baseline to Week 48
    BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts

    Secondary Outcome Measures

    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
    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
    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
    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
    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
    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
    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)
    Average change in CSFT from baseline over the period Week 36 through Week 48
    Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)
    Average change in CSFT from baseline over the period Week 4 to Week 48
    Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)
    Patient status regarding normal CSFT thickness (<280 microns) at each assessment visit
    Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)
    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)
    Average change in CSFTns from baseline over the period Week 36 through Week 48
    Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)
    Average change in CSFTns from baseline over the period Week 4 to Week 48
    Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)
    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)
    Proportion of patients with presence of leakage on FA at Week 48
    Assessed by fluorescein angiography
    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
    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.
    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.
    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.

    Full Information

    First Posted
    August 12, 2019
    Last Updated
    March 2, 2021
    Sponsor
    Novartis Pharmaceuticals
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04079231
    Brief Title
    Efficacy and Safety of Brolucizumab vs. Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema
    Acronym
    BUZZARD
    Official Title
    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)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    January 2021
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    This study was cancelled due to COVID-19.
    Study Start Date
    February 1, 2021 (Anticipated)
    Primary Completion Date
    January 31, 2023 (Anticipated)
    Study Completion Date
    January 31, 2023 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Novartis Pharmaceuticals

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    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).
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Diabetic Macula Edema
    Keywords
    Diabetic Macula Edema, Intravitreal injection, brolucizumab, aflibercept, double-masked

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Brolucizumab 6 mg
    Arm Type
    Experimental
    Arm Description
    Brolucizumab 6 mg/0.05 mL, 5 loading doses, with subsequent doses per protocol-specified maintenance schedule
    Arm Title
    Aflibercept 2 mg
    Arm Type
    Active Comparator
    Arm Description
    Aflibercept 2 mg/0.05 mL, as labeled, 5 loading doses, with subsequent doses every 8 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    Brolucizumab
    Other Intervention Name(s)
    RTH258, ESBA1008
    Intervention Description
    Intravitreal Injection
    Intervention Type
    Drug
    Intervention Name(s)
    Aflibercept
    Other Intervention Name(s)
    Eylea
    Intervention Description
    Intravitreal injection
    Primary Outcome Measure Information:
    Title
    Proportion of patients with a gain in Best Corrected Visual Acurity (BCVA) of ≥15 ETDRS letters at week 48
    Description
    BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts
    Time Frame
    Week 48
    Title
    Mean change in BCVA from baseline to Week 48
    Description
    BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts
    Time Frame
    Baseline, Week 48
    Secondary Outcome Measure Information:
    Title
    Change from baseline in BCVA averaged over a period Week 36 to Week 48
    Description
    BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts
    Time Frame
    Week 36, Week 48
    Title
    Proportion of patients with a gain in BCVA of ≥10 ETDRS letters from baseline to Week 48
    Description
    BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts
    Time Frame
    Baseline, Week 48
    Title
    Proportion of patients with a loss in BCVA of ≥15 ETDRS letters from baseline to Week 48
    Description
    BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts
    Time Frame
    Baseline, Week 48
    Title
    Proportion of patients with a loss in BCVA of ≥10 ETDRS letters from baseline to Week 48
    Description
    BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts
    Time Frame
    Baseline, Week 48
    Title
    Proportion of patients maintained at q12w up to Week 48
    Description
    Percentage of participants maintained at q12w (quarterly, every 12 weeks). This outcome measure is pre-specified for brolucizumab treatment arm only
    Time Frame
    Baseline, Week 48
    Title
    Proportion of patients maintained at q12w up to Week 48, within those patients that qualified for q12w at week 28
    Description
    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
    Time Frame
    Week 28, Week 48
    Title
    Change from baseline in central subfield thickness (CSFT, as determined by SD-OCT) at each assessment visit
    Description
    Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)
    Time Frame
    Baseline, Week 48
    Title
    Average change in CSFT from baseline over the period Week 36 through Week 48
    Description
    Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)
    Time Frame
    Week 36, Week 48
    Title
    Average change in CSFT from baseline over the period Week 4 to Week 48
    Description
    Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)
    Time Frame
    Week 4, Week 48
    Title
    Patient status regarding normal CSFT thickness (<280 microns) at each assessment visit
    Description
    Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)
    Time Frame
    Baseline, Week 48
    Title
    Change from baseline in Central Subfield Thickness-neurosensory (CSFTns, as determined by SD-OCT) at each assessment visit
    Description
    Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)
    Time Frame
    Baseline, week 48
    Title
    Average change in CSFTns from baseline over the period Week 36 through Week 48
    Description
    Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)
    Time Frame
    Baseline, Week 36, Week 48
    Title
    Average change in CSFTns from baseline over the period Week 4 to Week 48
    Description
    Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)
    Time Frame
    Baseline, Week 4, Week 48
    Title
    Proportion of patients with presence of SRF, IRF and simultaneous absence of SRF and IRF at each assessment visit
    Description
    Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)
    Time Frame
    Baseline, Week 48
    Title
    Proportion of patients with presence of leakage on FA at Week 48
    Description
    Assessed by fluorescein angiography
    Time Frame
    Week 48
    Title
    Change in ETDRS Diabetic Retinopathy Severity Scale (DRSS) score up to Week 48 (central reading)
    Description
    The Diabetic Retinopathy Disease Severity Scale measures the 5 levels of diabetic retinopathy - none, mild, moderate, severe, and proliferative
    Time Frame
    Baseline, Week 48
    Title
    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
    Description
    Disease status measured by ETDRS-DRSS. Diabetic Retinopathy Severity Scale (DRSS) score at each assessment visit.
    Time Frame
    Baseline, Week 48
    Title
    Incidence of progression to PDR as assessed by ETDRS-DRSS score of at least 61 by Week 48
    Description
    Incidence of progression to proliferative diabetic retinopathy (PDR) measured by ETDRS-DRSS. Diabetic Retinopathy Severity Scale (DRSS) score at each assessment visit.
    Time Frame
    Baseline, Week 48
    Title
    Rate of "inactive" PDRs by Week 48 compared to baseline
    Description
    Rate of "inactive" proliferative diabetic retinopathy (PDRs) by Week 48 compared to baseline as measured by Diabetic Retinopathy Severity Scale (DRSS) score.
    Time Frame
    Baseline, Week 48

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    110 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing 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.

    Learn more about this trial

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

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