To evaluate the efficacy and safety of brolucizumab in the treatment of patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO) and its potential to reduce the treatment burden for patients.
ID
Source
Brief title
Condition
- Vision disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To demonstrate that brolucizumab is non-inferior to aflibercept with respect to
the change in best-corrected visual acuity (BCVA) from baseline up to Month 6.
Secondary outcome
- To assess the effect of brolucizumab as compared to aflibercept on BCVA
- To evaluate the anatomical outcome with brolucizumab relative to aflibercept
- To evaluate the treatment frequency with brolucizumab during the
individualized flexible treatment (IFT) period relative to aflibercept
- To assess the safety and tolerability of brolucizumab relative to aflibercept
- To evaluate the effect of brolucizumab relative to aflibercept on
patient-reported vision-related quality of life
- To assess the immunogenicity of brolucizumab.
Background summary
Retinal vein occlusion (RVO) is the second most common retinal vascular
permeability disorder after diabetic retinopathy and is a significant cause of
visual impairment. Macular edema (ME) is the most common cause of vision loss
in patients with branch retinal vein occlusion (BRVO) or central retinal vein
occlusion (CRVO).
Anti-VEGF therapies have revolutionized the treatment of ME secondary to RVO
and are currently the standard of care in this indication as VEGF is a major
mediator for ME in RVO. The most commonly used VEGF inhibitors, i.e.
bevacizumab (Avastin®), aflibercept (Eylea®) and ranibizumab (Lucentis®) have
demonstrated compelling evidence for resolution of ME and improvement of VA
subsequent to the treatment with an anti-VEGF.
Ranibizumab, aflibercept and brolucizumab all inhibit the activity of VEGF-A
with all three having proven efficacy in the treatment of nAMD while both
ranibizumab and aflibercept have also previously demonstrated efficacy in the
treatment of patients with ME secondary to BRVO and CRVO. These findings
support the evaluation of brolucizumab in RVO patients. Furthermore, the
efficacy profile of brolucizumab in nAMD patients indicates a potential of
brolucizumab to differentiate versus existing anti-VEGFs on duration of action
and anatomical efficacy in CRVO patients.
Study objective
To evaluate the efficacy and safety of brolucizumab in the treatment of
patients with macular edema (ME) secondary to central retinal vein occlusion
(CRVO) and its potential to reduce the treatment burden for patients.
Study design
The study is an eighteen-month randomized, double-masked, multicenter,
activecontrolled, non-inferiority, 2-arm study in subjects with visual
impairment due to ME secondary to CRVO.
Subjects will be randomized in a 1:1 ratio to 1 of 2 treatment arms:
- Brolucizumab 6 mg: 6 x every 4 weeks (q4w) followed by 48 weeks of
individualized flexible treatment (IFT) from Week 24 onwards
- Aflibercept 2 mg: 6 x q4w followed by 48 weeks of IFT from Week 24 onwards.
Intervention
- Brolucizumab 6 mg/0.05 mL
- Aflibercept 2 mg/0.05 mL
Study burden and risks
Visits will be 21 times in 18 months. The visits usually last from 1 to 1,5
hours. The screening visit takes about 2,5 hours. All study procedures that are
applied are standard medical procedures, with the exception of questionnaires.
No complications caused by study procedures or treatments are expected. The
intended benefit for the patient is that it improves vision and that fewer
injections will be needed. In this study, the comparator is also an anti-VEGF
treatment, so there is no risk of sub-optimal treatment.
Haaksbergweg 16
Amsterdam 1101 BX
NL
Haaksbergweg 16
Amsterdam 1101 BX
NL
Listed location countries
Age
Inclusion criteria
- Signed informed consent must be obtained prior to participation in the study
- Male or female patients to be 18 years of age or over at screening - Patients
with visual impairment due to ME secondary to CRVO diagnosed less than 6 months
prior to screening; hemiretinal vein occlusion will be classified as CRVO
(study eye) - BCVA score between 78 and 23 letters, inclusive, using ETDRS
visual acuity testing charts (approximate Snellen equivalent of 20/32 to
20/320) at both screening and baseline (study eye)
Exclusion criteria
- Concomitant conditions or ocular disorders in the study eye at screening or
baseline which could, in the opinion of the investigator, prevent response to
study treatment or may confound interpretation of study results, compromise
visual acuity or require medical or surgical intervention during the first
12-month study period (e.g. structural damage of the fovea, vitreous
hemorrhage, retinal vascular occlusion other than BRVO, retinal detachment,
macular hole, or choroidal neovascularization of any cause, diabetic
retinopathy (except mild nonproliferative) and diabetic macular edema).
Hemiretinal vein occlusion should be excluded. - Any active intraocular or
periocular infection or active intraocular inflammation (e.g. infectious
conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis,
uveitis) in study eye at screening or baseline - Uncontrolled glaucoma in the
study eye defined as intraocular pressure (IOP) > 25 mmHg on medication, or
according to investigator's judgment, at screening or baseline - Presence of
amblyopia, amaurosis or ocular disorders in the fellow eye with BCVA < 20/200
at screening (except when due to conditions whose surgery may improve VA, e.g.
cataract) - Previous treatment with any anti-VEGF therapy or investigational
drugs in the study eye at any time prior to baseline - Previous use of
intraocular or periocular steroids in study eye at any time prior to baseline -
Macular laser photocoagulation (focal/grid) in the study eye at any time prior
to baseline and peripheral laser photocoagulation in the study eye within 3
months prior to the baseline - Intraocular surgery in the study eye during the
3-month period prior to baseline - Vitreoretinal surgery in the study eye at
any time prior to baseline - Aphakia with the absence of posterior capsule in
the study eye
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-001788-21-NL |
| ClinicalTrials.gov | NCT03810313 |
| CCMO | NL68931.100.19 |