Diabetic Macula EdemaPhase 3BUZZARDNCT04079231
Efficacy and Safety of Brolucizumab vs. Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema
A Phase 3 study testing Brolucizumab and Aflibercept in people with Diabetic Macula Edema, run by Novartis Pharmaceuticals.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 110 years
- Conditions the study is for
- Diabetic Macula Edema
- What is being tested?
- Brolucizumab and Aflibercept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Feb 2021to 31 Jan 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 110 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
About this study
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)
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).
Read the 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.
- Conditions
- Diabetic Macula Edema
- Being tested
- Brolucizumab, Aflibercept
- Keywords
- Diabetic Macula Edema, Intravitreal injection, brolucizumab, aflibercept, double-masked
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BrolucizumabDrug
Also called RTH258, ESBA1008
Intravitreal Injection
AfliberceptDrug
Also called Eylea
Intravitreal injection
| Study group | Role | What they receive |
|---|---|---|
| Brolucizumab 6 mg | Experimental | Brolucizumab 6 mg/0.05 mL, 5 loading doses, with subsequent doses per protocol-specified maintenance schedule Receives: Drug: Brolucizumab |
| Aflibercept 2 mg | Active comparator | Aflibercept 2 mg/0.05 mL, as labeled, 5 loading doses, with subsequent doses every 8 weeks Receives: Drug: Aflibercept |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: Baseline, Week 48
Secondary outcomes (19)
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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: Baseline, Week 48
Proportion of patients with presence of leakage on FA at Week 48
Assessed by fluorescein angiography
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline, Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Sep 2019
- Study start1 Feb 2021 (estimated)
- Primary completion31 Jan 2023 (estimated)
- Study completion31 Jan 2023 (estimated)
Why it stopped: This study was cancelled due to COVID-19.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetic Macula EdemaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04079231
- Sponsor's protocol ID
- CRTH258BDE01
- Acronym
- BUZZARD
- Status last verified
- Jan 2021
- First submitted
- 12 Aug 2019
- Last updated
- 4 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04079231
- Acronym / sponsor ID
- BUZZARD / CRTH258BDE01
- Conditions
- Diabetic Macula Edema
- Keywords
- Diabetic Macula Edema, Intravitreal injection, brolucizumab, aflibercept, double-masked
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: This study was cancelled due to COVID-19.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 1 Feb 2021 (estimated)
- Primary completion
- 31 Jan 2023 (estimated)
- Study completion
- 31 Jan 2023 (estimated)
- First posted
- 6 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Brolucizumab 6 mg | Experimental | Drug: BrolucizumabBrolucizumab 6 mg/0.05 mL, 5 loading doses, with subsequent doses per protocol-specified maintenance schedule |
| Aflibercept 2 mg | Active comparator | Drug: AfliberceptAflibercept 2 mg/0.05 mL, as labeled, 5 loading doses, with subsequent doses every 8 weeks |
Who may qualify
- Ages
- 18 to 110 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BrolucizumabAlso: RTH258, ESBA1008Intravitreal Injection | Drug | Brolucizumab 6 mg |
| AfliberceptAlso: EyleaIntravitreal injection | Drug | Aflibercept 2 mg |
Primary outcome
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
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
19 secondary outcomes
Change from baseline in BCVA averaged over a period Week 36 to Week 48
Time frame: 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
Proportion of patients with a loss in BCVA of ≥15 ETDRS letters from baseline to Week 48
Time frame: 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
Proportion of patients maintained at q12w up to Week 48
Time frame: 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
Change from baseline in central subfield thickness (CSFT, as determined by SD-OCT) at each assessment visit
Time frame: Baseline, Week 48
Average change in CSFT from baseline over the period Week 36 through Week 48
Time frame: Week 36, Week 48
Average change in CSFT from baseline over the period Week 4 to Week 48
Time frame: Week 4, Week 48
Patient status regarding normal CSFT thickness (<280 microns) at each assessment visit
Time frame: 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
Average change in CSFTns from baseline over the period Week 36 through Week 48
Time frame: 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
Proportion of patients with presence of SRF, IRF and simultaneous absence of SRF and IRF at each assessment visit
Time frame: Baseline, Week 48
Proportion of patients with presence of leakage on FA at Week 48
Time frame: Week 48
Change in ETDRS Diabetic Retinopathy Severity Scale (DRSS) score up to Week 48 (central reading)
Time frame: 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
Incidence of progression to PDR as assessed by ETDRS-DRSS score of at least 61 by Week 48
Time frame: Baseline, Week 48
Rate of "inactive" PDRs by Week 48 compared to baseline
Time frame: Baseline, Week 48
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2021.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Brolucizumab and Aflibercept in people with Diabetic Macula Edema, run by Novartis Pharmaceuticals.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 4 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients with a gain in Best Corrected Visual Acurity (BCVA) of ≥15 ETDRS letters at week 48 (time frame: Week 48). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2021.