MAAM Study: Avastin and Macugen Versus Avastin Versus Macugen

Study Overview
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Brief Summary
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The first results of Anti-Vascular Endothelial Growth Factor (VEGF) therapy were very promising and superior to established therapies. Three different substances (all of them applied intravitreally) are available, but comparative studies have not yet been conducted. In this pilot study, the safety (number of adverse events) and efficacy (distance acuity testing retinal thickness measurement) of Avastin and Macugen applied as monotherapy will be compared to a combined treatment of Avastin followed by Macugen used for retreatment. At least equal results of the combined therapy are expected.

Detailed Description
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The role of Vascular Endothelial Growth Factor (VEGF) in the pathogenesis of neovascular diseases like choroidal neovascularization (CNV) and proliferative diabetic retinopathy has been demonstrated in a series of publications. Therefore intravitreally applied VEGF antagonists have been used in the treatment of CNV in age-related macular degeneration (AMD) and diabetic cases. Three anti-VEGFs are available: Macugen® (Pegaptanib), Avastin® (Bevacizumab) and Lucentis® (Ranibizmab). Pegaptanib sodium is an aptamer designed to bind the VEGF 165 isoform with high affinity. Bevacizumab is a humanized monoclonal antibody to VEGF designed for intravenous administration and approved for the treatment of colorectal cancer. Ranibizumab is an anti-body binding site fragment that is derived from the same anti-VEGF antibody as bevacizumab. The decrease of retinal thickness measured in the OCT provides information concerning the amount of intraretinal fluid accumulation and therefore for the activity of a neovascular lesion. It has been proven that the aqueous humor levels of VEGF of eyes with CNV are significantly higher than those of eyes without ocular or systemic diseases. The retinal thickness and the VEGF concentration in the aqueous humor should give a good correlation to the anti vasogenic effect of the intravitreal treatment. In this study bevacizumab and pegaptanib as monotherapy should be compared with a combined therapy of bevacizumab applied first with pegaptanib used for retreatment. The benefit of this combined therapy should be that an initial blockage of all VEGF isoforms is necessary whereas for retreatment the blockage of the most important isoform in the pathogenesis of CNV is sufficient and the normal function of the retinal pigment epithelium and the choriocapillaris is not affected.

Official Title
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Comparison of Combined Therapy of Intravitreal Injection of Avastin and Macugen Versus Mono-Therapy The MAAM Study - a Pilot Study

Conditions
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Macular Degeneration

Intervention / Treatment
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* Drug: intravitreal injection of Bevacizumab (Avastin)
* Drug: Pegaptanib (Macugen)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 50 years Predominantly occult CNV Greatest diameter of the lesion < 5400µm Distance acuity > 0.1 Exclusion Criteria: Complicating general disorders inflicting with healing process Vision threatening diseases other than CNV Prior treatment for CNV Ophthalmic surgery within 4 weeks Not consented patients

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: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Avastin first followed by retreatment of Macugen | Drug: intravitreal injection of Bevacizumab (Avastin)<br>* 1.25 mg Avastin intravitreally applied once in arm 1 every 6 weeks in arm 2<br>Drug: Pegaptanib (Macugen)<br>* 0.3 mg intravitreally applied every 6 weeks as long as required<br>|
| Active Comparator: 2<br>Avastin intravitreally every 6 weeks | Drug: intravitreal injection of Bevacizumab (Avastin)<br>* 1.25 mg Avastin intravitreally applied once in arm 1 every 6 weeks in arm 2<br>|
| Active Comparator: 3<br>Macugen intravitreally every 6 weeks | Drug: Pegaptanib (Macugen)<br>* 0.3 mg intravitreally applied every 6 weeks as long as required<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| retinal thickness |  | 54 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| distance acuity |  | 54 weeks | 
| number of adverse events |  | 54 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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age-related Macular degeneration, Macugen, Avastin