A 12-month randomized, double-masked, multicenter, phase II study assessing safety and efficacy of Visudyne photodynamic therapy administered in conjunction with Lucentis versus Lucentis monotherapy in patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration

In de western world, also in The Netherlands, age-related macular degeneration
is the leading cause of blindness in individuals older than 50 years. With the
ongoing growth of this age-group, AMD is likely to become an increasing problem
to the public health.

Both Lucentis and Visudyne are approved and registered in The Netherlands for
treatment of age-related macular degeneration. In previous clinical trials it
was shown that Lucentis can stabilize or improve vision by inhibition of
neovascularization. Visudyne has shown to be able to prevent vision loss or
stabilize vision by occlusion of neovascular blood vessels. The combination of
the two therapies, acting through different modes of action, bears the
potential to provide a more convenient and less frequent therapy while
maintaining/improving the increase in vision improvement observed with Lucentis
monotherapy.

Het objectives of the study are to demonstrate that combination therapy of
Lucentis and Visudyne is not inferior in effectivity and safety to monotherapy
with Lucentis and to investigate whether less Lucentis injections in
combination therapy with Visudyne will achieve the same efficacy as Lucentis
monotherapy.
The results of this trial may help physicians refine the clinical management of
patients wih CNV secondary to age-related AMD.

In this 12-month, randomized, double-masked phase two trial, patients will be
randomised 1:1 to either combination therapy of Lucentis with Visudyne, or
Lucentis and sham PDT (placebo).

Lucentis: 0.05 ml intravitreal injection once per month during the first three
months. Then retreatment occurs based upon the monthly results of the different
eye assessments. The minimum interval between two injections is 30 days.
Visudyne: One intraveneus infusion with 15 mg Visudyne in 30 ml
5%-sucrose-solution and application of a cold laser during 83 seconds to
activate visudyne in the eye. Then retreatment occurs based upon the monthly
results of the different eye assessments. The minimum interval between two
infusions is 90 days.

The average duration of a study visit is three hours. During each visit, blood
pressure and pulse will be measured and a standard ophthalmologic exam will be
performed. At visit 3 and 12 the patient will be asked to complete a
questionnaire with 14 questions regarding treatment satisfaction. This will
take about 15 minutes per questionnaire. During visits 1, 3, 4, 5, 12 and as
needed during the other visits, a color fundus photograph will be taken and a
fundus angiogram will be performed. During visits 1, 3, 4, 5, 8, 11, 14 and as
needed during the other visits, an Optical coherence tomography (OCT) will be
performed.
Ten milliliters of blood will be collected from patients who agree to
participate in the pharmacogenetics study. In the future, genetic markers may
be found in these blood samples that can show a relationship between the
genetic information and mate waarin een patient op de behandeling met Lucentis
en Visudyne reageert en bijwerkingen ervaart.
From non-menopausal female patients, 4 ml of blood will be withdrawn once to
perform a pregnancy test. The risks of Lucentis and Visudyne treatment to an
unborn fetus are unknown and therefore, pregnant women will be excluded from
this study.
The side-effects of Lucentis include an increased eye pressure, eye infections
and eye inflammations. The eye pressure will be carefully monitored during the
trial and treated if necessary. The intravitreal injection procedure will be
performed under sterile circumstances and the patient will be asked to use
antimicrobial eye drops three days prior to and three days after a Lucentis
injection, to lower the chance on infections.
The side effects of Visudyne include back pain, fatigue and photosensitivity
reactions. By avoiding bright light for two days after the Visudyne treatment,
the chance of experiencing photosensitivity reaction will be reduced.