Combination Therapy for Age-Related Macular Degeneration.

Study Overview
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Brief Summary
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The primary purpose of the study is to investigate whether patients with Choroidal Neovascularization secondary to Age-related Macular Degeneration, receiving triple or double therapy compared to monotherapy with Avastin will reduce the intervention rate with equivalent safety and efficacy.

Detailed Description
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Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in developed countries throughout the world.The beneficial therapeutic effect of Photodynamic Therapy (PDT)in the treatment of AMD is modest. The treatment benefit of PDT may be moderated by PDT-induced, non-selective effects in the choroidal circulation (resulting in hypoxia-induced stimulation of angiogenesis through increased vascular endothelial growth factor (VEGF)production), direct injury to the retinal pigment epithelium, and subretinal fluid/hemorrhage or post-treatment inflammation secondary to PDT. There is potential that supplemental Avastin (through VEGF inhibition) or intravitreal Triamcinolone Acetonide (ITA) treatments (through non-specific membrane stabilizing, anti-neovascular, and anti-inflammatory activities) could minimize the effect of these processes, enhancing the efficacy of PDT. Presently, PDT, the current gold standard,in combination with Avastin and/or Kenalog is being more widely used in exactly this fashion and may become the standard of care without the necessary randomized clinical trial. However, the treatment benefit of these interventions is uncertain as is their safety profile. This randomized, controlled trial addresses the potential supplemental therapeutic effect of intravitreal injection of Triamcinolone Acetonide and/or Avastin in conjunction with photodynamic therapy for the treatment of sub-foveal CNVM secondary to AMD.

Official Title
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Combination Therapy in Neovascular Age-Related Macular Degeneration (AMD): A Three-armed, Randomized, Prospective Clinical Trial of Low Fluence Photodynamic Therapy(rPDT) With Adjunctive Avastin and Triamcinolone Acetonide (Kenalog)(Triple Therapy) Versus rPDT With Adjunctive Avastin (Double Therapy) Versus Monotherapy With Avastin.

Conditions
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Age Related Macular Degeneration

Intervention / Treatment
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* Drug: Avastin (Bevacizumab)
* Drug: Bevacizumab
* Drug: Bevacizumab
* Drug: Bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Choroidal neovascularization (CNV) secondary to age-related macular. All lesion subtypes, based upon IVFA evaluation will be included. CNV under the geometric centre of the foveal avascular zone. Evidence of choroidal neovascular activity as suggested by one of the following: sub-retinal lipid, sub-retinal hemorrhage, and documented loss of 3 lines of vision within the last three months. Greatest linear dimension of the lesion </= 5400 um. Visual acuity of between 20/32 and 20/800 in the study eye - Equivalent to Early Treatment of Diabetic Retinopathy Study (ETDRS) eye chart score of 5 to 75 letters at 2 metres. Willingness and ability to participate and provide written informed consent Exclusion Criteria: Individuals with choroidal neovascularization from causes other than AMD. Individuals physically unable to tolerate intravenous fluorescein angiography or Verteporfin injections. (Specifically, individuals with inadequate venous access or an allergy/sensitivity to fluorescein dye/porphyrins will be excluded.) Any intraocular surgery within 3 months in the study eye. Prior retinal or vitreous surgery including posterior segment vitrectomy or scleral buckling in the study eye. Any significant ocular disease that has compromised or could compromise vision in the study eye and confound analysis of the primary outcome. Individuals with physical or mental disabilities that prevent accurate vision testing. History of treatment of CNV in study eye other than extrafoveal confluent laser photocoagulation. Prior photodynamic therapy for CNV in the study eye. Active hepatitis or clinically significant liver disease Any patient with recent history of new onset cardiac disease or thromboembolic CNS event in the past. Subjects who are in an experimental therapy study or who have received experimental therapy within the last 12 weeks. Subjects who are a poor medical risk because of other systemic diseases or active uncontrolled infections. Women of child-bearing potential who are not on two forms of effective contraception during the trial and for at least 60 days following the last dose of study medications.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Reduced fluence PDT plus intravitreal Kenalog (2 mg) plus intravitreal Avastin 1.25 mg | Drug: Avastin (Bevacizumab)<br>* Avastin 1.25 mg intravitreal<br>Drug: Bevacizumab<br>* Intravitreal 1.25 mg<br>* Other names: Avastin;|
| Experimental: 2<br>Reduced fluence PDT plus intravitreal Avastin | Drug: Avastin (Bevacizumab)<br>* Avastin 1.25 mg intravitreal<br>Drug: Bevacizumab<br>* Intravitreal 1.25 mg<br>* Other names: Avastin;|
| Experimental: 3<br>Intravitreal Avastin and sham reduced fluence PDT | Drug: Avastin (Bevacizumab)<br>* Avastin 1.25 mg intravitreal<br>Drug: Bevacizumab<br>* Intravitreal Avastin 1.25 mg and sham reduced fluence PDT<br>* Other names: Avastin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To investigate whether patients with CNV secondary to AMD, receiving triple or double therapy compared to monotherapy with Avastin, will reduce the intervention rate with equivalent safety and efficacy. |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare between treatment groups: |  | 1 year | 
| Whether combination therapy with rPDT + iA and rPDT + iAK in patients with sub-foveal CNVM of all types secondary to ARMD will result in a significant improvement in visual acuity defined as 2 or more lines (10+ letters) on a standardized ETDRS chart c |  | 1 year | 
| Lesion growth and activity over the study period. |  | 1 year | 
| Contrast sensitivity. |  | 1 year | 
| The rate of cataract progression. |  | 1 year | 
| Central retinal thickness via Optical Coherence Tomography (OCT). |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Choroidal Neovascularization, Photodynamic Therapy, Age Related Macular Degeneration, Triamcinolone Acetonide, Avastin, Visudyne