Clinical trial NCT00413829: Immediate Effects of Lucentis® in Conjunction With Photodynamic Therapy With Visudyne® in Exudative AMD(IECOMB)
Official title: Open-label, Phase II Study Assessing Immediate Effects of Lucentis®(Ranibizumab) Administered in Conjunction With Photodynamic Therapy With Visudyne® in Patients With Choroidal Neovascularization Secondary to AMD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Age Related Macular Degeneration
Keywords: age related macular degeneration
anti-VEGF therapy
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2006-12-20
Enrollment: 20
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is an evaluation of the short term effects on CNV perfusion of a same-day administration of photodynamic therapy (PDT) with Visudyne® and an intravitreal injection of Lucentis® (ranibizumab, 0.3 mg). An evaluation of the short term effects on CNV perfusion of this combined treatment is needed for better understanding of treatment effects.

Detailed description: The primary objective is to quantify the short term effects on CNV perfusion of the same-day administration of photodynamic therapy with Visudyne® and an intravitreal injection of ranibizumab. These short term effects will be assessed with visual acuity measurements and ophthalmic examinations including indocyanine green (ICG) and fluorescein angiography (FA) as well as Optical Coherence Tomography (OCT) measurements. The primary variable for this assessment is the incidence of CNV closure one week after combined therapy as assessed with high speed ICG angiography. Fluorescein and ICG angiography will be performed using a scanning laser ophthalmoscope (HRA). All angiographic studies and OCT examinations will be evaluated by the Bern Photographic Reading Center in a masked fashion. Visual acuity assessments will be performed with Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts.

A secondary objective is to explore the effect of the same-day administration of photodynamic therapy with Visudyne® and an intravitreal injection of ranibizumab:

* on retinal thickness as measured by OCT over time
* in change of total lesion area, area of CNV assessed by FA
* in mean change of VA from baseline over time

Eligibility criteria: Inclusion Criteria:

* Patients 50 years of age or greater
* Patients with subfoveal choroidal neovascularization lesions secondary to AMD, either predominantly classic, occult, or minimally classic.
* CNV lesion in the study eye is ≤5400 microns in greatest linear dimension
* Patients who have a best corrected visual acuity (BCVA) score between 73 and 24 letters, inclusively, in the study eye using ETDRS-like grading charts (approximately 20/40 to 20/320) measured at 4 meters
* Willing to return for follow up scheduled visits for a 6 months period
* Only one eye will be assessed in the study. If both eyes are eligible, the one with the worse visual acuity will be selected for treatment and study unless, based on medical reasons, the investigator deems the other eye the more appropriate candidate for treatment and study

Exclusion Criteria:

* Patients who have a BCVA of \< 33 letters (approximately 20/200) in both eyes
* Prior treatment in the study eye with verteporfin, external-beam radiation therapy, vitrectomy, submacular surgery, other surgical intervention for AMD, or transpupillary thermotherapy
* Previous or current intravitreal drug delivery (e.g., intravitreal corticosteroid injection or device implantation) in the study eye
* Focal laser photocoagulation (juxta-, extra- or subfoveal ) in the study eye
* Concomitant use of chronic NSAIDs or steroids (by any route) for the duration of study participation (chronic use is defined as multiple doses taken daily for three or more consecutive days at any time during the study). Note that ASA (aspirin) taken as "low dose" up to 100 mg daily (qd) for prophylaxis of myocardial infarction (MI) and/or stroke is permitted during study
* Current use or likely need for systemic medications known to be toxic to the lens, retina or optic nerve, including Deferoxamine, Chloroquine/ hydroxychloroquine (Plaquenil), Tamoxifen, Phenothiazines and Ethambutol is excluded
* History of glaucoma filtration surgery, corneal transplant surgery or extracapsular extraction of cataract with phacoemulsification within six months preceding Day One, or a history of post-operative complications within the last 12 months preceding Day One in the study eye (uveitis, cyclitis etc.)
* History of uncontrolled glaucoma in the study eye (defined as intraocular pressure ≥ 25 mmHg despite treatment with topical anti-glaucomatous medication).
* Aphakia or absence of the posterior capsule in the study eye
* Previous violation of the posterior capsule in the study eye is also excluded unless it occurred as a result of YAG posterior capsulotomy in association with prior, posterior chamber intraocular lens implantation
* Spherical equivalent of the refractive error in the study eye demonstrating more than -8 diopters of myopia
* Presence of a retinal pigment epithelial tear involving the macula in the study eye
* Angioid streaks or precursors of CNV in either eye due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia
* Active intraocular inflammation (grade trace or above) in the study eye
* Any active infection involving an eyeball adnexa
* Vitreous hemorrhage or history of rhegmatogenous retinal detachment or macular hole (Stage 3 or 4) in the study eye

Primary outcomes:
measure: incidence of CNV closure one week after combined therapy as assessed with high speed ICG angiography
timeFrame: 24 months
Secondary outcomes:
measure: retinal thickness as measured by OCT over time
timeFrame: 24 months
measure: change of total lesion area, area of CNV and area of leakage over time as assessed by FA
timeFrame: 24 months
measure: mean change of VA from baseline over time
timeFrame: 24 months
Other outcomes:
Locations:
city: Bern
country: Switzerland
facility: Klinik und Poliklinik fuer Augenheilkunde, Inselspital
Study officials:
affiliation: Klinik und Poliklinik fuer Augenheilkunde, Inselspital
name: Sebastian Wolf, MD PhD
role: STUDY_CHAIR
affiliation: Klinik und Polklinik fuer Augenheilkunde, Inselspital
name: Ute Wolf-Schnurrbusch, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wolf-Schnurrbusch UE, Brinkmann CK, Berger L, Wolf S. Effects of combination therapy with verteporfin photodynamic therapy and ranibizumab in patients with age-related macular degeneration. Acta Ophthalmol. 2011 Sep;89(6):585-90. doi: 10.1111/j.1755-3768.2009.01747.x. Epub 2009 Oct 30.