A 24-month, phase IIIb, open-label, randomized, active-controlled,
3-arm, multicenter study assessing the efficacy and safety of an individualized,
stabilization-criteria-driven pro re nata (PRN) dosing regimen with 0.5-mg
ranibizumab intravitreal injections applied as monotherapy or with adjunctive laser
photocoagulation in comparison to laser photocoagulation in patients with visual
impairment due to macular edema secondary to branch retinal vein occlusion
(BRVO)

The present study will generate comparative data for 0.5-mg
ranibizumab using PRN dosing administered with or without adjunctive laser
treatment versus laser photocoagulation (the current standard of care) up to
Month 6
and will provide efficacy and safety data for 0.5-mg ranibizumab using PRN
dosing,
administered with or without adjunctive laser treatment, over 24 months in
patients
with visual impairment due to macular edema (ME) secondary to BRVO. Spectral
domain high-definition optical coherence tomography (OCT) images will be
explored
to gain insights into predictive factors for disease progression and the
possibility of
reduced monitoring will be assessed in Year 2. The results of this study will
provide
long-term safety and efficacy data to further guide recommendations on the use
of
ranibizumab in this indication.

Primary objective:
To demonstrate that an individualized stabilization-criteria-driven PRN dosing
regimen (PRN) with 0.5-mg ranibizumab administered with or without adjunctive
laser
treatment has superior efficacy as compared to the current standard of care,
laser
photocoagulation, in patients with visual impairment due to ME secondary to
BRVO.
The primary objective will be assessed by the mean best-corrected visual acuity
(BCVA) change at Month 6 compared to Baseline.
Key secondary objective:
To demonstrate in a first step that treatment with ranibizumab with adjunctive
laser is
non-inferior to treatment with ranibizumab monotherapy as assessed by the mean
average BCVA change from Month 1 through Month 24 compared to Baseline. To
demonstrate in a second step (after demonstrating non-inferiority) that
ranibizumab
with adjunctive laser reduces the number of ranibizumab retreatments as compared
to ranibizumab monotherapy by assessing the number of ranibizumab treatments
applied up to Month 23.

This is a phase IIIb, randomized, open-label, active-controlled, 3-arm,
multicenter study. Patients will be randomized in a 2:2:1 ratio to 1 of the 3
treatment
arms. Ranibizumab will be administered using a stabilization-criteria-driven PRN
dosing regimen. In addition to Screening and Baseline, there will be a visit on
Day 8
followed by monthly visits from Month 1 to Month 12. In Year 2, 12 monthly
visits may
occur, but the possibility to skip visits may reduce this number.

The investigational treatment in this study is
0.5-mg ranibizumab administered PRN by intravitreal injections, with or without
adjunctive laser treatment. The control treatment is laser photocoagulation
applied as
monotherapy. Patients will be assigned to one of the following 3 treatment arms
in a
ratio of 2:2:1.
• Arm 1: ranibizumab monotherapy
• Arm 2: ranibizumab with adjunctive laser
• Arm 3: laser monotherapy (option for ranibizumab as of Month 6)

27x: vital signs, ETDRS BCVA (visual sharpness), Ophthalmic examination,
tonometry en OCT scan
25x: Color fundus photography, Fluorescein angiography
24x: laser treatment
6x: NEI-VFQ-25 (questionnaire)

Ranibizumab can have the following side-effects:
Very common (10 or more in every 100 patients): bloodshot eye, eye pain, small
particles or spots in your vision, bleeding in the back of the eye, increased
eye pressure, displacement of the jelly-like portion inside the eye, troubling
of (a part of) the lens, inflammation of the eye, eye irritation, a feeling of
having something in the eye, visual disturbance, inflammation or infection of
the eyelid margins, formation of fibrous tissue under the retina, redness of
the eye, itching of the eye, dry eye, inflammation of the jelly-like portion
inside the eye, headache, runny nose and sore throat, back pain, pains in the
joints, elevated blood pressure, and decreasing number of red blood cells and
nausea.
Common (between 1 and 10 in every 100 patients): discomfort of the eye,
deposits in the back of the eye, bleeding at the site of the injection into the
eye, infection of the surface of the eye, infection of the eyeball, changes in
the part of the retina responsible for central vision, degeneration of the
retina, detachment of or rip in the retina or a layer of the retina causing
flashes of light with floaters and shadows progressing to a loss of sight,
blurred or decreased sharpness of vision, inflammation of the colored part of
the eye, the radial body (corpus ciliare) or an internal part of the eye,
little spots on the surface of the eye, bleeding of the eye, scratch or
inflammation of the cornea, increasing production of tears, discharge of the
eye with itching, redness and swelling, swelling of the eyelid, eyelid pain,
and sensitivity to light, infection of the lower part of the airways, flu,
urinary tract infection, stroke, anxiety, cough, and allergic reactions.
Uncommon (less than 1 in every 100 patients): changes in or thickening or
thinning of the central part of the surface of the eye, disorder in the back of
the eye or the jelly-like portion inside the eye, a specific type of glaucoma,
blindness, inflammatory deposits in the front part of the eye, pain or
irritation at the site of injection, abnormal sensation in the eye, irritation
of the eyelid, and accumulation of blood in the front part of the eye,
wheezing, increased secretion of the upper airways, changes in heart rhythm,
and inflammatory disease of the skin.
Finally, there are risks related to the procedures performed for study
purposes; the injection procedures and/or additional research procedures.