In this study we want to find out how safe and effective is the new product brolucizumab. Brolucizumab is administered in this study to subjects with decreased sight due to diabetes macular edema. The effects of brolucizumab are compared with those…
ID
Source
Brief title
Condition
- Retina, choroid and vitreous haemorrhages and vascular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To demonstrate that brolucizumab is noninferior to aflibercept with respect to
the visual outcome after the first year of treatment. Measured as change from
baseline in BCVA at Week 52.
Secondary outcome
- To demonstrate that brolucizumab is noninferior to aflibercept with respect
to visual outcome during the last 3 months of the first year of treatment
- To estimate the proportion of patients treated at q12w frequency with
brolucizumab
- To estimate the predictive value of the first q12w cycle for maintenance of
q12w treatment with brolucizumab
- To evaluate the functional and anatomical outcome with brolucizumab relative
to aflibercept
- To evaluate the effect of brolucizumab relative to aflibercept on the
Diabetic Retinopathy status
- To assess the safety and tolerability of brolucizumab relative to aflibercept
- To evaluate the effect of brolucizumab relative to aflibercept on
patient-reported outcomes (VFQ-25)
Background summary
Diabetic retinopathy (DR) and diabetic macular edema (DME) are common
microvascular complications in patients with diabetes and may have a
debilitating impact on visual acuity (VA), eventually leading to blindness.
For anti-VEGF agents like ranibizumab or aflibercept a favorable benefit risk
ratio was demonstrated with superior efficacy versus the previous standard of
care (laser photocoagulation) in large Phase 3 programs that consequently led
to their approval for the treatment of DME. Anti-VEGF treatment led to
clinically relevant improvements of BCVA, reduction of fluid accumulation and
decreased severity of diabetic retinopathy.
The current treatment options for patients with DME are: laser
photocoagulation, IVT corticosteroids, IVT corticosteroid implants, or IVT
anti-VEGF. Due to the efficacy and safety profile of anti-VEGF therapy, it has
become the first-line treatment. Corticosteroids are used as a second line
treatment and focal / grid laser photocoagulation remains a therapeutic option,
but with a lower expected benefit compared with steroid and anti-VEGF therapy.
Despite the treatment success of existing anti-VEGFs, there remains a need for
further treatment options to improve response rate and/or reduce resource use
and injection frequency in patients with DME.
Brolucizumab is a humanized single-chain fragment variable (scFv), binding to
VEGF-A.
Study objective
In this study we want to find out how safe and effective is the new product
brolucizumab. Brolucizumab is administered in this study to subjects with
decreased sight due to diabetes macular edema. The effects of brolucizumab are
compared with those of the long-standing drug aflibercept (brand name Eylea).
We want to assess the effects of both treatments. At this moment we do not know
which of the two treatments works best. That is why we are going to compare the
effects.
Study design
This study investigates the effects of brolucizumab and aflibercept in patients
with visual impairment due to fluid accumulation in the macula of the eye due
to diabetes. The research takes about 2 years. The study consists of the
screening of 2 weeks and a treatment period of approximately 100 weeks. There
are 29 visits in which various examinations are conducted to monitor the
patient's health and to investigate the effect and safety of the medication.
There are 3 study arms: 3 and 6 mg brolucizumab and 2mg aflibercept. Patients
are randomized into one of the treatment arms in the 1: 1: 1 ratio.
Intervention
The investigational treatments used in this study are:
* Brolucizumab 3 mg/0.05 mL
* Brolucizumab 6 mg/0.05 mL
The control treatment is:
* Aflibercept 2 mg/0.05 mL
-Brolucizumab 3 mg/0.05 mL 5 x q 6w loading then q12w/q8w maintenance
-Brolucizumab 6 mg/0.05 mL 5 x q6w loading then q12w/q8w maintenance
-Aflibercept 2 mg/0.05 mL 5 x q4w loading then q8w maintenance
Study burden and risks
Patients will have to come to the clinic 29 times in 102 weeks. Each visit will
take approximately 3 hours. All study procedures conducted at each visit are
standard medical procedures:
-Injection into the eye
-Eye drops used for eye examination
-OCT imaging and Fundus Photography
-Blood draws
No major complications caused by the study procedures or treatment are expected
Expected benefit is that sight of patients will improve. In this study placebo
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
General
- Patients must give written informed consent before any study related
assessments are performed
- Patients *18 years of age at baseline
- Patients with type 1 or type 2 diabetes mellitus and HbA1c of *10% at
screening
- Medication for the management of diabetes must have been stable within 3
months prior to randomization and is expected to remain stable during the
course of the study
Study Eye:
- Visual impairment due to DME with:
*BCVA score between 78 and 23 letters, inclusive, using Early Treatment
Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at a testing
distance of 4 meters (approximate Snellen equivalent of 20/32 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 *m on SDOCT at
screening If both eyes are eligible, the eye with the worse visual acuity will
be selected for study eye. However, the investigator may select the eye
with better visual acuity, based on medical reasons or local ethical
requirements.
Exclusion criteria
- Previous treatment with any anti-VEGF drugs or investigational drugs in the
study eye
- Active proliferative diabetic retinopathy in the study eye as per the
investigator
- Concomitant conditions or ocular disorders in the study eye at screening or
baseline which could, in the opinion of the investigator, interfere with study
results
- Any active intraocular or periocular infection or active intraocular
inflammation in study eye at screening or baseline
- Structural damage of the fovea in the study eye at screening likely to
preclude improvement in visual acuity following the resolution of macular edema.
- 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
- Neovascularization of the iris in the study eye at screening or baseline
- Evidence of vitreomacular traction in the study eye at screening or baseline
which, in the opinion of the investigator, affect visual acuity
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 | EUCTR2017-004742-23-NL |
| ClinicalTrials.gov | NCT03481634 |
| CCMO | NL64794.056.18 |