To evaluate the efficacy and safety of brolucizumab used in a Treat-to-Control (TtC) regimen for the treatment of patients with neovascular age-related macular degeneration (nAMD) with the objective to evaluate the potential to reduce treatment…
ID
Source
Brief title
Condition
- Vision disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To demonstrate that brolucizumab is superior to aflibercept with respect to the
duration of treatment intervals at Week 32
To demonstrate that brolucizumab is non-inferior to aflibercept with respect to
average change in best corrected visual acuity (BCVA) from baseline at Weeks 28
and 32
Secondary outcome
1. To evaluate the durability of brolucizumab relative to aflibercept
2. To evaluate the functional outcomes with brolucizumab relative to aflibercept
3. To evaluate the anatomical outcomes with brolucizumab relative to aflibercept
4. To evaluate the effect of brolucizumab relative to aflibercept on
Patient-Reported Outcomes (PRO)
5. To assess the safety and tolerability of brolucizumab relative to
aflibercept
Background summary
Age-related macular degeneration (AMD) is a major cause of severe loss of
vision in humans.
Age-related macular degeneration causes damage to the macula. There is a dry
and a wet form of macular degeneration. This study is performed in patients
with the wet form (nAMD). In the case of wet AMD, new blood vessels are formed
in the retina. However, these are of poor quality. Blood or fluid leaks through
the wall to the surrounding tissue. This leads to damage to, among other
things, the rods and cones of the retina, which play an important role in sharp
vision. As a result, sharp vision deteriorates further and further, especially
in the central part of the field of vision.
There is no treatment that addresses the cause of macular degeneration. The
main goal is to prevent the formation of new (bad) blood vessels and leakage
from the vessel wall. Anti-VEGF-therapies have revolutionized the treatment of
nAMD. The most commonly used VEGF inhibitors, i.e. bevacizumab (Avastin®),
aflibercept (Eylea®) and ranibizumab (Lucentis®) have shown convincing evidence
for the treatment of nAMD. Brolucizumab also belongs to this group of medicines
(anti-VEGF treatment).
The efficacy profile of brolucizumab in nAMD patients further indicates a
potential for brolucizumab to be associated with longer treatment intervals,
and thus fewer visits, than aflibercept, with similar visual results, based on
the recent results of previous studies (Hawk/Harrier).
Study objective
To evaluate the efficacy and safety of brolucizumab used in a Treat-to-Control
(TtC) regimen for the treatment of patients with neovascular age-related
macular degeneration (nAMD) with the objective to evaluate the potential to
reduce treatment frequencies
Study design
The study is a 64-week, randomized, double-masked, multi-center, active
controlled, two-arm study in patients with nAMD.
Patients will be randomized in a 1:1 ratio to one of the two treatment arms:
- Brolucizumab 6 mg : 3 x 4-week injections and one 8-week injection, followed
by Treat-to-Control treatment from Week 16 up to Week 60/62.
- Aflibercept 2 mg: 3 x 4-week injections and one 8-week injection, followed
by Treat-to-Control treatment from Week 16 up to Week 60/62.
Intervention
Brolucizumab 6 mg/0.05 mL
Aflibercept 2 mg/0.05 mL
Study burden and risks
Visits will take place 9-18 times in 15 months. Visits usually last 2-3 hours.
The screening visit lasts about 3.5 hours. All study procedures, with the
exception of questionnaires, are standard medical procedures. No complications
caused by study procedures or treatments are expected. The intended benefit for
the patient is improved vision and 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.
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 * 50 years of age at screening who are treatment
naive
- Active choroidal neovascularization (CNV) secondary to AMD that affects the
central subfield, including retinal angiomatous proliferation (RAP) with a CNV
component, confirmed by presence of active leakage from CNV seen by fluorescein
angiography and sequellae of CNV, e.g. pigment epithelial detachment (PED),
subretinal or sub-retinal pigment epithelium (sub-RPE) hemorrhage, blocked
fluorescence, macular edema (study eye)
- Presence of intraretinal fluid (IRF) or subretinal fluid (SRF) that affects
the central subfield, as seen by Spectral Domain Optical Coherence Tomography
(SD-OCT) (study eye)
- Best-corrected visual acuity (BCVA) score between 83 and 38 letters,
inclusive, using Early Treatment Diabetic Retinopathy Study (ETDRS) visual
acuity testing charts (approximate Snellen equivalent of 20/25 to 20/200) at
both screening and baseline visit (study eye)
Exclusion criteria
- Ocular conditions/disorders 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
planned medical or surgical intervention during the first 12-month study
period, structural damage of the fovea, atrophy or fibrosis at the center of
the fovea (study eye)
- Any active intraocular or periocular infection or active intraocular
inflammation, at screening or baseline (study eye)
- Uncontrolled glaucoma defined as intraocular pressure (IOP) > 25 mmHg on
medication, or according to investigator*s judgment, at screening or baseline
(study eye)
- Presence of amblyopia, amaurosis or ocular disorders in the fellow eye with
BCVA < 20/200 at screening (except when due to conditions which can lead to
improved VA after surgery eg cataract)
- Ocular treatments: previous treatment with any anti-vascular endothelial
growth factor (VEGF) drugs or investigational drugs, intraocular or periocular
steroids, macular laser photocoagulation, photodynamic therapy, vitreoretinal
surgery, intraocular surgery (study eye)
- Stroke or myocardial infarction during the 6-month period prior to baseline
- Systemic anti-VEGF therapy at any time.
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 | EUCTR2019-000716-28-NL |
| ClinicalTrials.gov | NCT04005352 |
| CCMO | NL70015.056.19 |