Evaluation of Macugen Treatment of Macular Edema Due to Branch Retinal Vein Occlusion

Open Label Macugen for the Treatment of Macular Edema Secondary to Branch Retinal Vein Occlusion

The purpose of this study is to evaluate the effect of intravitreal injections of Macugen every 6 weeks for the treatment of macular edema secondary to branch retinal vein occlusion (BRVO). We hypothesize that macular edema secondary to BRVO is mediated by VEGF 165 and that chronic suppression of VEGF 165 will successfully treat BRVO related macular edema.

Study Overview

• Status: Completed
• Conditions: Branch Retinal Vein Occlusion
• Intervention / Treatment: Drug: pegaptanib sodium (Macugen)

Detailed Description

Retinal venous occlusive disease, which includes central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO), is second only to diabetic retinopathy as a cause of vision loss due to retinal disease. The main cause of vision loss in all of these disorders is the development of macular edema. Current clinical practice based on randomized controlled clinical trials (ETDRS, BVOS) employs laser photocoagulation, either in a focal or grid pattern, to treat macular edema associated with diabetic retinopathy and branch retinal vein occlusion. Unfortunately, laser photocoagulation is ineffective in central retinal vein occlusion (CRVO), and no proven therapy exists for CRVO.

The pathogenesis of macular edema in retinal vascular diseases is generally accepted to be increased levels of vascular endothelial growth factor (VEGF) due to ischemic or other stimuli. VEGF is known to be one of the most potent stimulators of vascular leakage in humans. Therefore, it seems sensible to study inhibition of VEGF to reduce vascular leakage, reduce macular edema, and improve vision in these retinal vascular disorders.

Phase 2 randomized, controlled clinical trials of Macugen in diabetic macular edema and in macular edema associated with CRVO have been conducted. In the diabetes trial, patients treated with Macugen had improved vision, reduced macular edema as measured by optical coherence tomography (OCT), and reduced need for laser treatment compared to patients treated with sham injections. In the CRVO trial, patients treated with Macugen 1 mg every 6 weeks for 24 weeks had improved vision and reduced macular edema at week 30 compared to sham. This is the first randomized trial of treatment for CRVO to show a benefit over control. Based on these positive findings, we plan to study Macugen treatment of macular edema due to BRVO.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Jules Stein Eye Institute
  • Maryland
    • Hagerstown, Maryland, United States, 21740
      • Cumberland Valley Retina Center
  • South Carolina
    • West Columbia, South Carolina, United States, 29169
      • Palmetto Retina Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Macular edema secondary to BRVO involving the foveal center in male or female patients at least 18 years of age
• Duration of BRVO macular edema less than 6 months prior to baseline visit
• Best corrected ETDRS visual acuity 20/40-20/320 (Snellen equivalent) using the 4 meters testing method.
• Central foveal thickness greater than or equal to 250 microns using the OCT-3
• Less than 25% of foveal capillary ring disruption
• Less than 2 disc areas of capillary non-perfusion within 1000 microns of the foveal center
• Absence of hemorrhage or lipid in the foveal center
• Investigator comfortable deferring macular laser for 18 weeks from baseline and intravitreous steroid for 36 weeks from baseline

Exclusion Criteria:

• Ocular conditions other than BRVO related macular edema such as significant cataract, diabetic retinopathy, AMD, glaucoma, uveitis, epiretinal membrane, vitreomacular traction or tumor.
• Intraocular surgery within past 3 months
• Significant enlargement of foveal avascular zone(>25% disruption of capillary ring) or greater than 2 disc areas of nonperfusion within 1000 microns of foveal center.
• Likelihood of evidence driven indication for peripheral photocoagulation in the next 6 months.
• Patients who have shown evidence of spontaneous improvement within the preceding 3 months, as determined by an improvement of >15 letters of vision or thinning of the Center Point on OCT of >20% from baseline determination
• Prior grid laser within 4 months of baseline or more than one prior grid laser treatment.
• No prior intravitreous or periocular steroid injections in the study eye.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Pegaptanib Sodium 0.3mg (Macugen); Intravitreous injections of Macugen 0.3mg given at baseline, week 6 and week 12 with subsequent injections at six weekly intervals at the discretion of the investigator until week 54.	Drug: pegaptanib sodium (Macugen); Subjects were randomized 3:1 to intravitreous injections of pegaptanib 0.3mg or 1mg at baseline and at weeks 6 and 12 with subsequent injections at 6-week intervals at investigator discretion until week 48.; Other Names: Macugen
Active Comparator: Pegaptanib Sodium 1 mg (Macugen); Intravitreous injections of Macugen 1.0mg given at baseline, week 6 and week 12 with subsequent injections at six weekly intervals at the discretion of the investigator until week 54.	Drug: pegaptanib sodium (Macugen); Subjects were randomized 3:1 to intravitreous injections of pegaptanib 0.3mg or 1mg at baseline and at weeks 6 and 12 with subsequent injections at 6-week intervals at investigator discretion until week 48.; Other Names: Macugen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in ETDRS Best Corrected Visual Acuity From Baseline at 54 Weeks	54 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Standardized Change From Baseline in Macular Thickening Measured by OCT3 Using the Central Point of the Central Subfield		54 Weeks
Safety Parameters	Safety endpoints incuded all investigator reported ocular and systemic adverse events. All events were graded as mild moderate or severe and assessed as related or unrelated to the injection procedure and the study drug.	54 Weeks
Change in Central Subfield Thickness on OCT From Baseline to Week 54		54 Weeks
Change in Macular Volume on OCT From Baseline to Week 54		54 Weeks

Collaborators and Investigators

• Sponsor: Palmetto Retina Center, LLC
• Collaborators: Pfizer; Eyetech Pharmaceuticals
• Investigators: Principal Investigator: John A Wells, III, MD, Palmetto Retina Center, LLC

Publications and helpful links

General Publications

• Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group. Arch Ophthalmol. 1985 Dec;103(12):1796-806.
• Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, Pasquale LR, Thieme H, Iwamoto MA, Park JE, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med. 1994 Dec 1;331(22):1480-7. doi: 10.1056/NEJM199412013312203.
• Argon laser photocoagulation for macular edema in branch vein occlusion. The Branch Vein Occlusion Study Group. Am J Ophthalmol. 1984 Sep 15;98(3):271-82. doi: 10.1016/0002-9394(84)90316-7.
• Evaluation of grid pattern photocoagulation for macular edema in central vein occlusion. The Central Vein Occlusion Study Group M report. Ophthalmology. 1995 Oct;102(10):1425-33. doi: 10.1016/s0161-6420(95)30849-4.
• Cunningham ET Jr, Adamis AP, Altaweel M, Aiello LP, Bressler NM, D'Amico DJ, Goldbaum M, Guyer DR, Katz B, Patel M, Schwartz SD; Macugen Diabetic Retinopathy Study Group. A phase II randomized double-masked trial of pegaptanib, an anti-vascular endothelial growth factor aptamer, for diabetic macular edema. Ophthalmology. 2005 Oct;112(10):1747-57. doi: 10.1016/j.ophtha.2005.06.007.
• Funatsu H, Yamashita H, Ikeda T, Nakanishi Y, Kitano S, Hori S. Angiotensin II and vascular endothelial growth factor in the vitreous fluid of patients with diabetic macular edema and other retinal disorders. Am J Ophthalmol. 2002 Apr;133(4):537-43. doi: 10.1016/s0002-9394(02)01323-5.

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: November 30, 2006
• First Submitted That Met QC Criteria: December 1, 2006
• First Posted (Estimate): December 4, 2006

Study Record Updates

• Last Update Posted (Estimate): September 12, 2014
• Last Update Submitted That Met QC Criteria: September 10, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: macular edema; branch retinal vein occlusion; vascular endothelial growth factor; pegaptanib sodium
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Retinal Degeneration; Retinal Diseases; Embolism and Thrombosis; Venous Thrombosis; Thrombosis; Macular Degeneration; Macular Edema; Retinal Vein Occlusion
• Other Study ID Numbers: PRC-001; Pfizer Reference # 20050548