Efficacy of Ranibizumab in Combination With Photodynamic Therapy for Wet Age-Related Macular Degeneration - Full Text View

Purpose

The purpose of the investigators study is to look at the visual outcomes of Ranibizumab injections in combination with photodynamic therapy for the treatment of neovascular age-related macular degeneration.

Condition	Intervention	Phase
Macular Degeneration Visual Acuity	Drug: Ranibizumab	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Efficacy of Ranibizumab (Lucentis) in Combination With Photodynamic Therapy for Neovascular Age-Related Macular Degeneration

Resource links provided by NLM:

Genetics Home Reference related topics: age-related macular degeneration X-linked juvenile retinoschisis

MedlinePlus related topics: Macular Degeneration

Drug Information available for: Verteporfin Ranibizumab

U.S. FDA Resources

Further study details as provided by McGill University Health Center:

Primary Outcome Measures:

Mean change from baseline at 6 months in the best corrected visual acuity (VA) score using an early treatment diabetic retinopathy study eye chart at a starting distance of 4 meters. [ Time Frame: Monthly for a total of 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To determine the following: 1:Proportion of subjects who loose fewer than 15 letters from baseline visual acuity at 6 months 2: Proportion of subjects with VA of 20/200 or worse 3: Proportion of subjects with VA of 20/40 or better [ Time Frame: One year ] [ Designated as safety issue: No ]

Estimated Enrollment:	180
Study Start Date:	January 2009
Estimated Study Completion Date:	December 2009
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Pre-PDT Participants in this group will receive an intraocular Ranibizumab injection one week prior to the first PDT with verteporfin.	Drug: Ranibizumab Intraocular injection of 0.5mg of Ranibizumab one week prior to PDT with verteporfin Other Name: Lucentis the brand name of Ranibizumab
Active Comparator: Post-PDT Participants in this group will receive an intraocular Ranibizumab injection one week post the first PDT with verteporfin.	Drug: Ranibizumab Intraocular injection of 0.5mg of Ranibizumab one week after PDT with verteporfin Other Name: Lucentis the brand name of Ranibizumab
Active Comparator: No PDT Participants in this group will receive an intraocular Ranibizumab injection with no accompanying PDT with verteporfin.	Drug: Ranibizumab Intraocular injection of 0.5mg of Ranibizumab with no accompanying PDT with verteporfin Other Name: Lucentis the brand name of Ranibizumab

Detailed Description:

The main cause of severe vision loss in patients with age-related macular degeneration (AMD) is the development of choroidal neovascularization (CNV). This debilitating form of AMD affects the macula lutea, the central part of the retina, which is responsible for high resolution visual acuity. Characteristic findings in neovascular AMD include the development of new, abnormal blood vessels in the choroid layer beneath the macula otherwise known as CNV.

Current treatment options for this condition have included include laser therapy, photodynamic therapy (PDT), and intraocular injections (different types of anti-vascular endothelial growth factors) alone or in combination. While current treatments were demonstrated to slow the progression of vision loss, neither therapy was shown to significantly improve visual acuity.

Given their different modes of action, it is believed that combination therapy of Ranibizumab with PDT may lead to better visual outcomes and may result in an improved effect in treating AMD and therefore may help decrease the need for monthly Ranibizumab injections. After the first injection, regardless of which group the patient has been assigned to, they will receive Ranibizumab injections at 4 week intervals if clinically indicated. The purpose of the this study is to evaluate the visual outcomes of intraocular Ranibizumab injections in combination with photodynamic therapy with verteporfin for the treatment of neovascular AMD.

Eligibility

Ages Eligible for Study:	50 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

diagnosed with any subtype of primary subfoveal or juxtafoveal choroidal neovascularization
must be 50 years of age or older
have a lesion whose total size is no more than 5400micrometres in greatest linear dimension in the study eye
CNV that is more than 50% obscured by blood
have best corrected visual acuity of 20/50-20/320 (Snellen equivalent)
have been assessed with the use of early treatment diabetic retinopathy study charts

Exclusion Criteria:

previous treatment (including verteporfin therapy) that could compromise an assessment of the study treatment
any permanent structural damage to the central fovea

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00813891

Contacts

Contact: John Galic, MD	514-285-8866
Contact: Karin Oliver, MD	514-285-8866	karin.oliver@hotmail.com

Locations

Canada, Quebec
The Royal Victoria Hospital and the Montreal Retinal Institute	Not yet recruiting
Montreal, Quebec, Canada, H3Z 1P4

Sponsors and Collaborators

McGill University Health Center

Investigators

Principal Investigator:	John Galic, MD	Montreal Retina Institute
Principal Investigator:	John Chen, MD	Montreal Retina Institute

More Information

Additional Information:

Royal Victoria Hospital is one of the sites that the study will take place. This link exits the ClinicalTrials.gov site

Publications:

Gragoudas ES, Adamis AP, Cunningham ET Jr, Feinsod M, Guyer DR; VEGF Inhibition Study in Ocular Neovascularization Clinical Trial Group. Pegaptanib for neovascular age-related macular degeneration. N Engl J Med. 2004 Dec 30;351(27):2805-16.

Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, Kim RY; MARINA Study Group. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006 Oct 5;355(14):1419-31.

Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY, Sy JP, Schneider S; ANCHOR Study Group. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006 Oct 5;355(14):1432-44.

Bressler NM, Bressler SB, Congdon NG, Ferris FL 3rd, Friedman DS, Klein R, Lindblad AS, Milton RC, Seddon JM; Age-Related Eye Disease Study Research Group. Potential public health impact of Age-Related Eye Disease Study results: AREDS report no. 11. Arch Ophthalmol. 2003 Nov;121(11):1621-4.

Klein R, Peto T, Bird A, Vannewkirk MR. The epidemiology of age-related macular degeneration. Am J Ophthalmol. 2004 Mar;137(3):486-95. Review.

Congdon N, O'Colmain B, Klaver CC, Klein R, Muñoz B, Friedman DS, Kempen J, Taylor HR, Mitchell P; Eye Diseases Prevalence Research Group. Causes and prevalence of visual impairment among adults in the United States. Arch Ophthalmol. 2004 Apr;122(4):477-85.

Friedman DS, O'Colmain BJ, Muñoz B, Tomany SC, McCarty C, de Jong PT, Nemesure B, Mitchell P, Kempen J; Eye Diseases Prevalence Research Group. Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol. 2004 Apr;122(4):564-72.

Bressler NM. Age-related macular degeneration is the leading cause of blindness... JAMA. 2004 Apr 21;291(15):1900-1. No abstract available.

Resnikoff S, Pascolini D, Etya'ale D, Kocur I, Pararajasegaram R, Pokharel GP, Mariotti SP. Global data on visual impairment in the year 2002. Bull World Health Organ. 2004 Nov;82(11):844-51. Epub 2004 Dec 14.

Yannuzzi LA, Negrão S, Iida T, Carvalho C, Rodriguez-Coleman H, Slakter J, Freund KB, Sorenson J, Orlock D, Borodoker N. Retinal angiomatous proliferation in age-related macular degeneration. Retina. 2001;21(5):416-34.

Holz FG, Pauleikhoff D, Klein R, Bird AC. Pathogenesis of lesions in late age-related macular disease. Am J Ophthalmol. 2004 Mar;137(3):504-10. Review.

Lopez PF, Sippy BD, Lambert HM, Thach AB, Hinton DR. Transdifferentiated retinal pigment epithelial cells are immunoreactive for vascular endothelial growth factor in surgically excised age-related macular degeneration-related choroidal neovascular membranes. Invest Ophthalmol Vis Sci. 1996 Apr;37(5):855-68.

Frank RN, Amin RH, Eliott D, Puklin JE, Abrams GW. Basic fibroblast growth factor and vascular endothelial growth factor are present in epiretinal and choroidal neovascular membranes. Am J Ophthalmol. 1996 Sep;122(3):393-403.

Kvanta A, Algvere PV, Berglin L, Seregard S. Subfoveal fibrovascular membranes in age-related macular degeneration express vascular endothelial growth factor. Invest Ophthalmol Vis Sci. 1996 Aug;37(9):1929-34.

Kliffen M, Sharma HS, Mooy CM, Kerkvliet S, de Jong PT. Increased expression of angiogenic growth factors in age-related maculopathy. Br J Ophthalmol. 1997 Feb;81(2):154-62.

Otani A, Takagi H, Oh H, Koyama S, Ogura Y, Matumura M, Honda Y. Vascular endothelial growth factor family and receptor expression in human choroidal neovascular membranes. Microvasc Res. 2002 Jul;64(1):162-9. No abstract available.

Rakic JM, Lambert V, Devy L, Luttun A, Carmeliet P, Claes C, Nguyen L, Foidart JM, Noël A, Munaut C. Placental growth factor, a member of the VEGF family, contributes to the development of choroidal neovascularization. Invest Ophthalmol Vis Sci. 2003 Jul;44(7):3186-93.

Okamoto N, Tobe T, Hackett SF, Ozaki H, Vinores MA, LaRochelle W, Zack DJ, Campochiaro PA. Transgenic mice with increased expression of vascular endothelial growth factor in the retina: a new model of intraretinal and subretinal neovascularization. Am J Pathol. 1997 Jul;151(1):281-91.

Schwesinger C, Yee C, Rohan RM, Joussen AM, Fernandez A, Meyer TN, Poulaki V, Ma JJ, Redmond TM, Liu S, Adamis AP, D'Amato RJ. Intrachoroidal neovascularization in transgenic mice overexpressing vascular endothelial growth factor in the retinal pigment epithelium. Am J Pathol. 2001 Mar;158(3):1161-72.

Krzystolik MG, Afshari MA, Adamis AP, Gaudreault J, Gragoudas ES, Michaud NA, Li W, Connolly E, O'Neill CA, Miller JW. Prevention of experimental choroidal neovascularization with intravitreal anti-vascular endothelial growth factor antibody fragment. Arch Ophthalmol. 2002 Mar;120(3):338-46.

Saishin Y, Saishin Y, Takahashi K, Lima e Silva R, Hylton D, Rudge JS, Wiegand SJ, Campochiaro PA. VEGF-TRAP(R1R2) suppresses choroidal neovascularization and VEGF-induced breakdown of the blood-retinal barrier. J Cell Physiol. 2003 May;195(2):241-8.

Verteporfin Roundtable 2000 and 2001 Participants; Treatment of age-related macular degeneration with photodynamic therapy (TAP) study group principal investigators; Verteporfin in photodynamic therapy (VIP) study group principal investigators. Guidelines for using verteporfin (visudyne) in photodynamic therapy to treat choroidal neovascularization due to age-related macular degeneration and other causes. Retina. 2002 Feb;22(1):6-18. Review.

Responsible Party:	McGill University Health Center, McGill Ophthalmology
ClinicalTrials.gov Identifier:	NCT00813891 History of Changes
Other Study ID Numbers:	MUHC - 1234 - RVH
Study First Received:	December 22, 2008
Last Updated:	December 22, 2008
Health Authority:	Canada: Health Canada

Keywords provided by McGill University Health Center:

ranibizumab
verteporfin

Additional relevant MeSH terms:

Macular Degeneration
Wet Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
Verteporfin

Photosensitizing Agents
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Pharmacologic Actions
Dermatologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 22, 2013