Efficacy and Safety of Brolucizumab vs. Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema
- Registration Number
- NCT04079231
- Lead Sponsor
- Novartis Pharmaceuticals
- 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.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Aflibercept 2 mg Aflibercept Aflibercept 2 mg/0.05 mL, as labeled, 5 loading doses, with subsequent doses every 8 weeks Brolucizumab 6 mg Brolucizumab Brolucizumab 6 mg/0.05 mL, 5 loading doses, with subsequent doses per protocol-specified maintenance schedule
- Primary Outcome Measures
Name Time Method Mean change in BCVA from baseline to Week 48 Baseline, Week 48 BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts
Proportion of patients with a gain in Best Corrected Visual Acurity (BCVA) of ≥15 ETDRS letters at week 48 Week 48 BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts
- Secondary Outcome Measures
Name Time Method Proportion of patients maintained at q12w up to Week 48 Baseline, 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 with presence of SRF, IRF and simultaneous absence of SRF and IRF at each assessment visit Baseline, Week 48 Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)
Proportion of patients with presence of leakage on FA at Week 48 Week 48 Assessed by fluorescein angiography
Rate of "inactive" PDRs by Week 48 compared to baseline 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.
Proportion of patients maintained at q12w up to Week 48, within those patients that qualified for q12w at week 28 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
Change from baseline in Central Subfield Thickness-neurosensory (CSFTns, as determined by SD-OCT) at each assessment visit Baseline, week 48 Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)
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 Baseline, Week 48 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 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.
Proportion of patients with a loss in BCVA of ≥15 ETDRS letters from baseline to Week 48 Baseline, Week 48 BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts
Average change in CSFTns from baseline over the period Week 36 through Week 48 Baseline, Week 36, 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 Baseline, Week 4, Week 48 Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)
Proportion of patients with a loss in BCVA of ≥10 ETDRS letters from baseline to Week 48 Baseline, Week 48 BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts
Change from baseline in central subfield thickness (CSFT, as determined by SD-OCT) at each assessment visit Baseline, Week 48 Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)
Average change in CSFT from baseline over the period Week 36 through Week 48 Week 36, Week 48 Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)
Patient status regarding normal CSFT thickness (<280 microns) at each assessment visit Baseline, Week 48 Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)
Change in ETDRS Diabetic Retinopathy Severity Scale (DRSS) score up to Week 48 (central reading) Baseline, Week 48 The Diabetic Retinopathy Disease Severity Scale measures the 5 levels of diabetic retinopathy - none, mild, moderate, severe, and proliferative
Change from baseline in BCVA averaged over a period Week 36 to Week 48 Week 36, 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 Baseline, Week 48 BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts
Average change in CSFT from baseline over the period Week 4 to Week 48 Week 4, Week 48 Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)