A 56-week phase IIIb/IV, open-label, one-arm extension study to assess the efficacy and safety of brolucizumab 6mg in a Treat-to-Control regimen with maximum treatment intervals up to 20 weeks for the treatment of patients with neovascular Age-related Macular Degeneration who have completed the CRTH258A2303 (TALON) study

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
brolucizumab to be associated with longer
treatment intervals, and thus fewer visits, than aflibercept, with similar
visual results and comparable safety, based on the results of previous studies
(Hawk/Harrier).
Since the first marketing authorization approval in October 2019 for the
treatment of nAMD, adverse events of retinal vasculitis and/or retinal vascular
occlusion, that may result in severe vision loss and typically in the presence
of intraocular inflammation, have been reported from
post-marketing experience with brolucizumab (Beovu®). Considering these events,
the overall risk/benefit assessment remains positive.
The ongoing core study CRTH258A2303 (TALON) intends to complement the current
clinical dataset on brolucizumab by generating new evidence based on the T&E
concept prevalent in the current management of patients with nAMD. It will be
comparing the efficacy and safety of brolucizumab and aflibercept administered
in an identical 4-week-adjustment Treat-to-Control regimen with treatment
intervals from 4 to 16 weeks.
This study, CRTH258A2303E1, is an extension study of the CRTH258A2303 (TALON)
study, aiming at gathering additional long-term efficacy and safety evidence
about brolucizumab in a TtC treatment regimen with treatment intervals further
extended up to 20 weeks in nAMD. It intends to contribute to the growing
clinical dataset of brolucizumab by generating supplementary evidence on
treatment safety, efficacy, and durability in nAMD.

The purpose of this study is to evaluate the efficacy and safety of
brolucizumab used in a Treat- to-Control (TtC) regimen with maximum treatment
intervals up to 20 weeks for the treatment of patients with neovascular
age-related macular degeneration (nAMD) who have completed
the CRTH258A2303 study (TALON). In addition, switch data from aflibercept to
brolucizumab is collected.

Primary Objectives:
To evaluate the extended durability of brolucizumab in a Treat-to-Control
regimen assessed as duration of the last interval with no disease activity up
to Week 56.
To evaluate the functional outcomes of brolucizumab in a Treat-to-Control
regimen assessed as average change of best corrected visual acuity
from baseline at week 52 and week 56

This is a 56-week, one-arm, open-label, multi-center extension study where all
patients are to be treated with brolucizumab up to week 52 in a
Treat-to-Control regimen with treatment intervals up to maximum 20 weeks

Brolucizumab 6 mg/0.05 mL

Visits will take place 4-14 times in 56 weeks. Visits usually last 2-3 hours.
All study procedures 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.