MAAM Study: Avastin and Macugen Versus Avastin Versus Macugen

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

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.

Study Overview

• Status: Completed
• Conditions: Macular Degeneration
• Intervention / Treatment: Drug: intravitreal injection of Bevacizumab (Avastin); Drug: Pegaptanib (Macugen)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, A1030
    • Ludwig Boltzmann Institute for Retinology and Biomicroscopic Lasersurgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
retinal thickness	54 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: The Ludwig Boltzmann Institute of Retinology and Biomicroscopic Laser Surgery
• Investigators: Principal Investigator: Ilse Krebs, MD, Ludwig Boltzmann Institute for Biomicroscopic Lasersurgery

Study record dates

Study Major Dates

• Study Start: July 1, 2006
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: September 15, 2007
• First Submitted That Met QC Criteria: September 17, 2007
• First Posted (Estimate): September 18, 2007

Study Record Updates

• Last Update Posted (Estimate): July 2, 2009
• Last Update Submitted That Met QC Criteria: June 30, 2009
• Last Verified: October 1, 2008

More Information

Terms related to this study

• Keywords: Avastin; age-related Macular degeneration; Macugen
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: EK06-001839-18