CRTH258B2301 Brolucizumab vs Aflibercept in Diabetic Macular Oedema
Research type
Research Study
Full title
A Two-Year, Three-Arm, Randomized, Double-Masked,Multicenter, Phase III Study assessing the Efficacy and Safety of Brolucizumab versus Aflibercept in Adult Patients with Visual Impairment due to Diabetic Macular Oedema
IRAS ID
231957
Contact name
Geeta Menon
Contact email
Sponsor organisation
Novartis Pharma AG
Eudract number
2017-004742-23
Clinicaltrials.gov Identifier
Duration of Study in the UK
2 years, 11 months, days
Research summary
Research Summary
Diabetes is a common disease affecting 2 to 5% of the world population. DMO is a common complication in patients with diabetes and may eventually lead to blindness. 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 oedema (DMO).The current treatment options for patients with DMO are anti-VEGF treatment, laser treatment and corticosteroid treatment. Due to the efficacy and safety profile of anti-VEGF therapies, such as ranibizumab or aflibercept they have become the first-line treatment options for DMO. Like, ranibizumab and aflibercept, brolucizumab, the treatment under investigation, is an anti-VEGF treatment approved for the treatment of age-related macular degeneration. The profile of brolucizumab in previous trials indicates a potential for it to reduce the number and frequency of treatments required to effectively treat DMO, thus reducing the treatment burden of patients and healthcare institutions and supporting the initiation of this study.
The study population under investigation will be male and female patients 18 years old and over with visual impairment due to DMO. It is planned that 534 patients will be treated in the study at approximately 110 centres worldwide. Approximately 20 patients from 4 centres will be from the UK.
Summary of Results
• Non-inferiority of brolucizumab 6 mg to aflibercept 2 mg was demonstrated on visual acuity for the primary endpoint and the key secondary endpoint in this study in the Year 1 analysis (Study B2301 Week 52 Interim CSR dated 08-Oct-2021). However, non-inferiority of brolucizumab 3 mg to aflibercept 2 mg was not achieved. This supports brolucizumab 6 mg as the therapeutic dose for vision improvement in subjects with DME.• The overall results of efficacy and safety at Week 100 were consistent to those at Week 52 (primary analysis) and key results are as follows:
o Brolucizumab 6 mg administered q6w during the loading phase and q12w/q8w thereafter for the maintenance phase improved visual outcomes and led to a marked reduction in CSFT comparable to the standard of care, whereas lower proportions of subjects with presence of retinal fluid were consistently observed with brolucizumab 6 mg compared to aflibercept 2 mg during the maintenance phase (Week 40 through Week 100).
o Nearly half (44.1%) of the subjects receiving brolucizumab 6 mg with q12w treatment regimen during the maintenance phase demonstrated the potential for brolucizumab to reduce patient burden based on lasting disease control. A clinically relevant improvement in the proportion of subjects with a ≥2-step and ≥3-step improvement from baseline in the ETDRS DRSS score at Week 100 was observed with brolucizumab 6 mg.
o The overall safety of brolucizumab was comparable with that of aflibercept 2 mg over 2 years of treatment. Intraocular inflammation was reported in 4.2% of subjects in the brolucizumab 6 mg arm, 5.3% in the brolucizumab 3 mg arm and 1.1% in the aflibercept arm, of which no new event of retinal vasculitis was reported in any treatment arms during Year 2. The 5 retinal vascular occlusion events reported during Year 2 in 4 subjects were not associated with IOI or retinal vasculitis.
o The data from Year 2 further reinforce the value of brolucizumab 6 mg as a therapy for patients with visual impairment due to DME and a therapy which can address the unmet medical need for long-acting effective disease control with reduced treatment and monitoring burden.
REC name
South Central - Berkshire B Research Ethics Committee
REC reference
18/SC/0371
Date of REC Opinion
16 Aug 2018
REC opinion
Further Information Favourable Opinion