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

Diabetic Macula Edema Clinical Trial

— 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)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04079231
• Other study ID #: CRTH258BDE01
• Status: Withdrawn
• Phase: Phase 3
• Start date: February 1, 2021
• Est. completion date: January 31, 2023

Study information

• Verified date: January 2021
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 31, 2023
• Est. primary completion date: January 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 110 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetic Macula Edema
• Edema
• Macular Edema
• Vision Disorders
• Vision, Low

Intervention

Drug:
• Brolucizumab
Intravitreal Injection
• Aflibercept
Intravitreal injection

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Patient status regarding normal CSFT thickness (<280 microns) at each assessment visit	Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)	Baseline, Week 48
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Proportion of patients with presence of leakage on FA at Week 48	Assessed by fluorescein angiography	Week 48
Secondary	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
Secondary	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
Secondary	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
Secondary	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