Brolucizumab Efficacy and Safety Single-Arm Descriptive Trial in Patients With Persistent Diabetic Macular Edema
NCT Number: NCT06498050
Acronym: BEST
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE4
Conditions: Diabetic Macular Edema
Interventions: DRUG: intravitreal injection of Brolucizumab 6 mg in study eye
Sponsor: Guangdong Provincial People's Hospital
Collaborators: Beijing Novartis Pharma
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 52
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-07-09
Completion Date: 2025-07-31
Locations: Guangdong Provincial People's Hospital, Guangzhou, Guangdong, 510000, China

Summary:
The goal of this clinical trial is to evaluate the efficacy of brolucizumab 6 mg in Chinese patients with persistent diabetic macular edema (DME). It will also learn about the safety of brolucizumab 6 mg.

The main questions it aims to answer are:

Does brolucizumab 6 mg reduce central subfield thickness (CST) and improve best-corrected visual acuity (BCVA) of participants? What medical problems do participants have after receiving intravitreal injections of brolucizumab 6 mg? Researchers will compare baseline CST and BCVA to those at each post-baseline visit to see if brolucizumab 6 mg works to treat persistent DME.

Participants will:

Receive brolucizumab 6 mg via intravitreal injections following two treatment patterns:

Treatment Pattern 1: every 6 weeks for 5 injections Treatment Pattern 2: every 6 weeks for 3 injections followed by 1 injection after 12 weeks Visit the clinic 8 times for treatment and assessments over the course of 28 weeks

Primary Outcome Measures: The proportion of patients with central subfield thickness (CST) <300 μm assessed by Spectral Domain Optical Coherence Tomography (SD-OCT), Central subfield thickness (CST) will be measured by Spectral Domain Optical Coherence Tomography (SD-OCT). The measurement of CST refers to the mean retinal thickness of the circular area within 1 mm in diameter that centered on the fovea. SD-OCT images will be captured for the study eye using SD-OCT equipment., Baseline, week 28
Secondary Outcome Measures: The proportion of patients with Best Corrected Visual Acuity (BCVA) improvement of ≥5 letters assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing chartstesting charts, Best Corrected Visual Acuity (BCVA) was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Eligible participants will be those with a BCVA ETDRS letter score ranging from 78 to 23 (approximate Snellen equivalent of 20/32 to 20/320) in the study eye. The scoring system for visual function ranges from 0 to 100, with higher score indicating better visual function., Baseline, week 28
Other Outcome Measures: Change from baseline in BCVA at each post-baseline visit assessed by ETDRS visual acuity testing charts, Best Corrected Visual Acuity (BCVA) was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Eligible participants will be those with a BCVA ETDRS letter score ranging from 78 to 23 (approximate Snellen equivalent of 20/32 to 20/320) in the study eye. The scoring system for visual function ranges from 0 to 100, with higher score indicating better visual function., Baseline, week 1, week 6, week 12, week 16, week 18, week 24, week 28|The proportion of patients with gain in BCVA of ≥5, ≥10 and ≥15 letters assessed by ETDRS visual acuity testing charts at each post-baseline visit from baseline, Best Corrected Visual Acuity (BCVA) was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Eligible participants will be those with a BCVA ETDRS letter score ranging from 78 to 23 (approximate Snellen equivalent of 20/32 to 20/320) in the study eye. The scoring system for visual function ranges from 0 to 100, with higher score indicating better visual function., Baseline, week 1, week 6, week 12, week 16, week 18, week 24, week 28|The proportion of patients with change in BCVA of <5 letters assessed by ETDRS visual acuity testing charts at each post-baseline visit from baseline, Best Corrected Visual Acuity (BCVA) was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Eligible participants will be those with a BCVA ETDRS letter score ranging from 78 to 23 (approximate Snellen equivalent of 20/32 to 20/320) in the study eye. The scoring system for visual function ranges from 0 to 100, with higher score indicating better visual function., Baseline, week 1, week 6, week 12, week 16, week 18, week 24, week 28|The proportion of patients with loss in BCVA of ≥5, ≥10 and ≥15 letters assessed by ETDRS visual acuity testing charts at each post-baseline visit from baseline, Best Corrected Visual Acuity (BCVA) was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Eligible participants will be those with a BCVA ETDRS letter score ranging from 78 to 23 (approximate Snellen equivalent of 20/32 to 20/320) in the study eye. The scoring system for visual function ranges from 0 to 100, with higher score indicating better visual function., Baseline, week 1, week 6, week 12, week 16, week 18, week 24, week 28|Change in CST assessed by SD-OCT at each post-baseline visit/ CST change from baseline, Central subfield thickness (CST) will be measured by Spectral Domain Optical Coherence Tomography (SD-OCT). The measurement of CST refers to the mean retinal thickness of the circular area within 1 mm in diameter that centered on the fovea. SD-OCT images will be captured for the study eye using SD-OCT equipment., Baseline, week 1, week 6, week 12, week 16, week 18, week 24, week 28|The proportion of patients with central subfield thickness (CST) <300 μm assessed by SD-OCT at each post-baseline visit, Central subfield thickness (CST) will be measured by Spectral Domain Optical Coherence Tomography (SD-OCT). The measurement of CST refers to the mean retinal thickness of the circular area within 1 mm in diameter that centered on the fovea. SD-OCT images will be captured for the study eye using SD-OCT equipment., Baseline, week 1, week 6, week 12, week 16, week 18, week 24, week 28|The proportion of patients with central subfield thickness (CST) <280 μm assessed by SD-OCT at each post-baseline visit, Central subfield thickness (CST) will be measured by Spectral Domain Optical Coherence Tomography (SD-OCT). The measurement of CST refers to the mean retinal thickness of the circular area within 1 mm in diameter that centered on the fovea. SD-OCT images will be captured for the study eye using SD-OCT equipment., Baseline, week 1, week 6, week 12, week 16, week 18, week 24, week 28|The proportion of patients with presence of Subretinal Fluid (SRF), Intraretinal Fluid (IRF) and simultaneous absence of SRF and IRF assessed by qualitative and quantitative criteria based on SD-OCT at each post-baseline visit, Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) will be evaluated in images captured for the study eye using SD-OCT equipment., Baseline, week 1, week 6, week 12, week 16, week 18, week 24, week 28|Change in subretinal Fluid (SRF) and Intraretinal Fluid (IRF) assessed by quantitative criteria based on SD-OCT from baseline, The volume of SRF and IRF will be calculated in SD-OCT images using artificial intelligence algorithms., Baseline, week 28|Change in vessel densities of deep capillary plexus (DCP), superficial capillary plexus (SCP) and radial peripapillary capillaries (RPC), and foveal avascular zone (FAZ) area based on optical coherence tomography-angiography from baseline, Optical coherence tomography-angiography (OCT-A) is a dye-less and non-invasive angiographic technique that offers a three-dimension imaging of the retinal circulation. It enables visualizing the movement of particles within blood vessels, predominantly red blood cells, across the entire retinal and choroidal vascular layers., Baseline, week 28|The proportion of patients with a ≥2- and ≥3-step improvement or worsening from baseline assessed by the ETDRS Diabetic Retinopathy Severity Scale (DRSS) score, The Early Treatment Diabetic Retinopathy Study Diabetic Retinopathy Severity Scale (DRSS) is a standard approach to measure diabetic retinopathy (DR) severity. Wide-field fundus color photography images were obtained and assessed in the study eye by fundus color photography machines., Baseline, week 28|The proportion of patients with presence of leakage assessed by qualitative and quantitative criteria based on Fluorescein angiography (FA), Fluorescein Angiography (FA) is an invasive eye examination that uses an injected dye to illuminate the retinal and choroidal blood vessels, offering a dynamic, real-time assessment of blood flow and leakage, Baseline, week 28|Change in aqueous cytokine levels assessed by immunological methods from baseline, The cytokines detected in aqueous humor will be quantitatively assessed by immunological methods., immediately before the first injection at week 1, immediately before the last injection at week 24|The proportion of patients in every treatment pattern, There are 2 treatment patterns depending on the disease activity assessment at week 18. Treatment Pattern 1: every 6 weeks for 5 injections; Treatment Pattern 2: every 6 weeks for 3 injections followed by 1 injection after 12 weeks., Baseline, week 28|Incidence and characteristics of ocular and non-ocular adverse events, An adverse event is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings, symptom or disease) in a clinical investigation The ocular adverse events will be assessed by slip-lamp examination, intraocular pressure from non-contact tonometry, and retinal circulation from optical coherence tomography angiography.

The non-ocular adverse events will be assessed by vital signs, complete blood count, biochemical profile, glycosylated hemoglobin A1c, urinary albumin to creatinine ratio, serum pregnancy test, and urine pregnancy test., Baseline, week 28