Triple Therapy - PDT Plus IVD and Intravitreal Ranibizumab Versus Lucentis Monotherapy to Treat Age-Related Macular Degeneration

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to compare triple therapy using Photodynamic therapy, intravitreal Dexamethasone and intravitreal Ranibizumab injections versus monotherapy with intravitreal Ranibizumab alone for the treatment of Age-Related Macular Degeneration.

Detailed Description
-----------------
This is a twelve month Phase II prospective masked study comparing Group 1 triple therapy: Same day combination therapy with PDT, 500 microgram dose (0.05cc) intravitreal dexamethasone injection (10mg/ml vial), and a single 0.5 mg intravitreal Ranibizumab injection. This will be compared to Group 2 monotherapy: one intravitreal injection of 0.5 mg Lucentis given every four weeks on a set dosing schedule. Sixty consecutive patients will be enrolled into this clinical trial utilizing the current standard of care guidelines as used at Bay Area Retina Associates. Angiography, fundus photography will be performed at the initial visit and quarterly follow-up visits. Only OCT testing will be performed at all other follow-up visits. Both groups will be re-evaluated for safety at 12 and 24 months. Group 1 Following the initial treatment, all future re-treatments with Lucentis will be determined on a PRN basis. The decision will be based on clinical examination and imaging evidence of lesion activity. Any evidence of subretinal fluid or cystoid edema on OCT or clinical examination, or evidence of leakage on angiogram will result in re-treatment. If after three consecutive Ranibizumab injections in Group 1, there is any evidence of lesion recurrence or growth of the neovascular membrane associated with visual decline or persistent subretinal fluid, the patient will be treated with repeat PDT/IVD/Lucentis The decision to retreat Group 1 with ranibizumab at each monthly follow-up visit will be dependent on clinical exam, OCT measurements or angiographic findings as documented below. Group 2 Subjects will receive one intravitreal injection of 0.5 mg Lucentis every four weeks until week 48 or as indicated on the FDA approval label.

Official Title
-----------------
A Prospective Masked Pilot Study Comparing Group 1 Triple Therapy - PDT Plus IVD and Intravitreal Ranibizumab Versus Group 2 Monotherapy - Intravitreal Ranibizumab Alone.

Conditions
-----------------
Age Related Macular Degeneration

Intervention / Treatment
-----------------
* Drug: ranibizumab, dexamethasone and verteporfin
* Drug: Ranibizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Best Corrected Visual Acuity using ETDRS Charts between 20/32 and 20/400 (Snellen Equivalent) in the study eye with evidence of neovascular ARMD. (Only one eye will be eligible for study. If both eyes are eligible, the one with the better visual acuity will be selected for treatment unless, based on medical reasons, the investigator deems the other eye to be more appropriate for treatment and study.) All lesion subtypes will be enrolled with the following criteria Predominantly classic: Classic lesion greater than 50% of the total lesion area Lesion must be less than 12 disc areas Minimally classic or occult: CNVM must be greater than or equal to 50% of the total lesion size. There must be some evidence of recent disease progression (heme, vision loss, recent lesion growth on FA) Lesion size must be less than 12 disc areas. Occult: Lesions must show recent activity progression with respect to vision, subretinal hemorrhage or subretinal fluid Less than 12 disc areas in total size Signed informed consent Age greater than or equal to 50 years Exclusion Criteria: Pigment epithelial detachment greater than 50% of the total lesion size Previous treatment for ARMD in the study eye Previous intravitreal drug delivery in the study eye History of vitrectomy in the study eye Fibrosis or atrophy involving the center of the fovea in the study eye Neovascular membrane from any other concurrent retinal disease such as high myopia (SER > -8D), histoplasmosis or other ocular inflammatory disease. Known history of glaucoma and on more than one topical medication History of glaucoma filtering surgery in the study eye History of corneal transplant in the study eye Patients with co-existing macular disease such as diabetic macular edema Active intraocular inflammation in the study eye History of allergy to fluorescein not amenable to treatment Inability to comply with study or follow up procedures

Ages Eligible for Study
-----------------
Minimum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Group 1<br>Combination triple therapy of Lucentis, Dexamethasone and Visudyne Therapy | Drug: ranibizumab, dexamethasone and verteporfin<br>* One 500 microgram dose (0.05cc) intravitreal dexamethasone (10 mg/ml vial) in combination with Visudyne Photodynamic Therapy and 0.5 mg intravitreal Ranibizumab injection on the same day.<br>|
| Other: Group 2<br>Monotherapy: One 0.5 mg intravitreal Ranibizumab injection | Drug: Ranibizumab<br>* One 0.5 mg intravitreal Ranibizumab injection<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Acuity: Change in visual acuity by 15 or more ETDRS letters at 6 and 12 months. Non-inferiority as compared to the triple therapy arm will serve to determine efficacy for the purposes of this pilot trial. |  | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lesion size |  | one year | 
| Lesion leakage |  | one year | 
| OCT measurement of macular thickness, subretinal fluid and cystoid edema |  | one year | 
| Total number of treatments required |  | one year | 
| Timing of visual improvement after initiation of therapy |  | one year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Macular Degeneration, Degenerative changes in the macula lutea of the retina., Maculopathy, Age-Related, Age-Related Maculopathies, Age-Related Maculopathy, Maculopathies, Age-Related, RETINAL DEGENERATION, ARMD, AMD, Lucentis, Visudyne, Photodynamic Therapy, Verteporfin, Ranibizumab, Intravitreal Dexamethasone