Diabetic Macula Edema
Conditions
Keywords
Diabetic Macula Edema, Intravitreal injection, brolucizumab, aflibercept, double-masked
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.
Interventions
DRUGBrolucizumab
Intravitreal Injection
DRUGAflibercept
Intravitreal injection
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 110 Years
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 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 (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) |
| 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) |
| 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 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 |
| 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 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 |
| 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 |
| 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. |
| 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. |
| 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) |
| 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 |
Outcome results
None listed