A Phase 3, Multicentre, Double-masked, Randomised Study to Evaluate the Efficacy and Safety of Intravitreal OPT-302 in Combination with Aflibercept, Compared with Aflibercept Alone, in Participants with Neovascular Age-related Macular Degeneration (nAMD) (COAST)

Age-related macular degeneration (AMD) is a chronic degenerative eye disease of
the central retina, that causes a progressive, irreversible, severe loss of
central vision. In many countries, AMD leads to as many blind registrations
than all other eye diseases combined. There are two main types of AMD: dry-AMD
and neovascular AMD (nAMD). Although nAMD is less common, affecting only 10% of
AMD patients, it is more likely to lead to significant vision loss and
blindness. Visual deterioration associated with nAMD can be rapid, generally
severe, and significantly deteriorates patients* quality of life.
There is a high unmet medical need for more effective treatments in patients
with sub-optimal responses to current treatments for nAMD (primarily
intravitreally administered vascular endothelial growth factor A [VEGF-A]
inhibitors). The investigational product, 2.0 mg OPT-302, is a therapeutic
candidate for the treatment of nAMD, and when co-administered with a VEGF-A
inhibitor, it is expected to provide improved responses compared to treatment
with an anti-VEGF-A therapy alone.
Based on the positive Phase 2b study results from study OPT-302-1002, Opthea is
conducting a prospective Phase 3 programme in treatment-naïve participants with
nAMD, which comprises of two Phase 3 studies: (i) intravitreal of 2.0 mg
OPT-302 in combination with 0.5 mg ranibizumab (OPT-302-1004) and of (ii)
intravitreal 2.0 mg OPT-302 in combination with 2.0 mg aflibercept
(OPT-302-1005), compared with 0.5 mg ranibizumab or 2.0 mg aflibercept, with
sham control in each trial respectively.

This study has been transitioned to CTIS with ID 2024-512880-30-00 check the CTIS register for the current data.

To determine the efficacy of intravitreal 2.0 mg OPT-302 when administered in
combination with intravitreal 2.0 mg aflibercept, in participants with
neovascular AMD.

Phase 3, multicentre, randomised, parallel-group, sham-controlled,
double-masked, superiority study

Three study arms, randomised in a 1:1:1 ratio:
• Standard Dosing 2.0 mg OPT-302 (50 µl) intravitreal injection at 4-weekly
intervals (q4w), with 2.0 mg aflibercept (50 µl) intravitreal injection (3
doses at 4-weekly intervals, and then 8-weekly [q4w x 3 then q8w]).
• Extended Dosing 2.0 mg OPT-302 (50 µl) intravitreal injection (q4w x 3 then
q8w) with sham injection at visits when OPT-302 is not administered, with 2.0
mg aflibercept (50 µl) intravitreal injection (q4w x 3 then q8w).
• Control Sham intravitreal injection 4-weekly, with 2.0 mg aflibercept (50 µl)
intravitreal injection (q4w x 3 then q8w).

Burden: Subject*s participation will last a total of approximately about 23
months and 2 weeks and is divided into 3 periods: screening period, treatment
period, and a final study visit. After the screening period, there will be a
Baseline visit (Visit 2) within 2 weeks of the first visit (screening visit).
The treatment period will have 25 planned visits to the study centre. Prior to
each injection, the subject will be given numbing drops. Aside from the
intervention, participation in the study involves eye exams, physical exam,
vital signs measurements, blood draws and urine collection. Participants will
be subjected to a diary and questionnaires for completion, as well as to the
review of their medical history. Risks: A total of 399 participants have
received eye injections with the study drug, OPT-302, to date. The study drug
alone or in combination with aflibercept was reported to be well tolerated. The
very common side effects of the study drug (OPT-302) (seen in more than 1 in 10
participants) in participants who received the study drug in combination with
aflibercept were conjunctival haemorrhage (blood spots in the white of the
eye), increased intraocular pressure (increase in eye pressure in the eyes),
These side effects were reported in the study eye. The common side effects
(seen in up to 1 in 10 participants) in participants who received the study
drug in combination with aflibercept were eye pain, vitreous floaters (black
grey spots or strings in vision that drift across the eyes), eye irritation,
punctate keratitis (condition that causes red watery eyes, light sensitivity,
and decreased vision), increased lacrimation (watering eyes), ocular hyperaemia
(redness of the eye), anterior chamber cell - this is a sign there is
inflammation in the eye, blurred vision. These side effects were reported in
the study eye. There may be other unforeseen risks that can occur. Risk-benefit
analyses: There is a high unmet medical need for more effective treatments in
patients with sub-optimal responses to current treatments for nAMD (primarily
intravitreally administered vascular endothelial growth factor A [VEGF-A]
inhibitors). The investigational product, 2.0 mg OPT-302, is a therapeutic
candidate for the treatment of nAMD, and when co-administered with a VEGF-A
inhibitor, it is expected to provide improved responses compared to treatment
with an anti-VEGF-A therapy alone. Almost 400 participants have received >1,800
intravitreal injections of OPT-302 (any dose) during the clinical programme to
date, of which 282 participants have received 1,515 intravitreal injections in
combination with 0.5 mg ranibizumab, and 104 participants have received 288
intravitreal injections in combination with 2.0 mg aflibercept. Based on the
studies conducted, there appears to be no significant additional safety risks
associated with the addition of OPT-302 to ranibizumab or aflibercept
intravitreal therapy over and above those identified after intravitreal
injection of anti-VEGF-A therapies. The risk profile in relation to the high
unmet medical need supports a favorable benefit/risk ratio for this study of
OPT-302.