Clinical trial NCT00061594: A Study to Compare rhuFab V2 With Verteporfin Photodynamic in Treating Subfoveal Neovascular Macular Degeneration
Official title: A Phase III, Multicenter, Randomized, Double Masked, Active Treatment-Controlled Study of the Efficacy and Safety of rhuFab V2 (Ranibizumab) Compared With Verteporfin (Visudyne) Photodynamic Therapy in Subjects With Predominantly Classic Subfoveal Neovascular Age-Related Macular Degeneration
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Macular Degeneration
Keywords: Neovascular age-related macular degeneration
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2003-05-30
Enrollment: 426
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: This is a phase III, multicenter, randomized, double-masked, active treatment-controlled study of intravitreally administered ranibizumab compared with verteporfin (Visudyne) photodynamic therapy (PDT) in treating subfoveal neovascular mascular degeneration.


Eligibility criteria: Inclusion Criteria:

* Signed informed consent
* Age \>=50 years
* Eligibility for treatment with PDT using verteporfin in the study eye according to the Visudyne product labeling
* Future treatment with PDT using verteporfin anticipated or expected in the study eye
* Primary or recurrent subfoveal choroidal neovascularization (CNV) lesions secondary to age-related macular degeneration (AMD) in the study eye
* A classic CNV component (well-demarcated hyperfluorescence boundaries in the early phase of the fluorescein angiogram) that is \>=50% of the total lesion size
* Total lesion size of less than or equal to 5400 um in greatest linear dimension (GLD)
* Best corrected visual acuity, using Early Treatment of Diabetic Retinopathy Study (ETDRS) charts, of 20/40 to 20/320 (Snellen equivalent) in the study eye

Exclusion Criteria:

* Prior treatment with verteporfin, external-beam radiation therapy, or transpupillary thermotherapy (TTT) in the study eye
* Treatment with verteporfin in the non-study eye less than 7 days preceding Day 0
* Previous participation in a clinical trial (for either eye) involving anti angiogenic drugs (pegaptanib, ranibizumab, anecortave acetate, protein kinase C inhibitors, etc.)
* Previous intravitreal drug delivery (e.g., intravitreal corticosteroid injection or device implantation) in the study eye
* Previous subfoveal focal laser photocoagulation in the study eye
* Laser photocoagulation (juxtafoveal or extrafoveal) in the study eye within 1 month preceding Day 0
* History of vitrectomy surgery in the study eye
* History of submacular surgery or other surgical intervention for AMD in the study eye
* Previous participation in any studies of investigational drugs within 1 month preceding Day 0 (excluding vitamins and minerals)
* Subretinal hemorrhage in the study eye that involves the center of the fovea, if the size of the hemorrhage is either \>=50% of the total lesion area or \>=1 disc area (DA) in size
* Subfoveal fibrosis or atrophy in the study eye
* CNV in either eye due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia
* Retinal pigment epithelial tear involving the macula in the study eye
* Any concurrent intraocular condition in the study eye (e.g., cataract or diabetic retinopathy) that, in the opinion of the Investigator could either: (1) Require medical or surgical intervention during the 24-month study period to prevent or treat visual loss that might result from that condition, or (2) If allowed to progress untreated, could likely contribute to loss of at least 2 Snellen equivalent lines of best corrected visual acuity over the 24-month study period
* Active intraocular inflammation (grade trace or above) in the study eye
* Current vitreous hemorrhage in the study eye
* History of rhegmatogenous retinal detachment or macular hole (Stage 3 or 4) in the study eye
* History of idiopathic or autoimmune-associated uveitis in either eye
* Infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye
* Aphakia or absence of the posterior capsule in the study eye
* Spherical equivalent of the refractive error in the study eye demonstrating more than -8 diopters of myopia
* Intraocular surgery (including cataract surgery) in the study eye within 2 months preceding Day 0
* Uncontrolled glaucoma in the study eye (defined as intraocular pressure \>=30 mmHg despite treatment with anti-glaucoma medication)
* History of glaucoma filtering surgery in the study eye
* History of corneal transplant in the study eye
* Premenopausal women not using adequate contraception
* History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect interpretation of the results of the study or render the subject at high risk for treatment complications
* Current treatment for active systemic infection
* History of allergy to fluorescein, not amenable to treatment
* Inability to obtain fundus photographs or fluorescein angiograms of sufficient quality to be analyzed and graded by the central reading center
* Inability to comply with study or follow up procedures

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Retina Centers, P.C.
state: Arizona
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Beverly Hills
country: United States
facility: Retina-Vitreous Associates Medical Group
state: California
city: Irvine
country: United States
facility: UC Irvine
state: California
city: Los Angeles
country: United States
facility: Doheny Eye Institute
state: California
city: Menlo Park
country: United States
facility: California Vitreoretinal Research Center
state: California
city: Mountain View
country: United States
facility: No. California Retina-Vitreous Associates
state: California
city: San Francisco
country: United States
facility: UCSF School of Medicine
state: California
city: Danbury
country: United States
facility: Danbury Eye Physicians & Surgeons
state: Connecticut
city: Hamden
country: United States
facility: New England Retina Associates
state: Connecticut
city: Daytona Beach
country: United States
facility: Florida Retina Institute
state: Florida
city: Ft. Lauderdale
country: United States
facility: Retina Vitreous Consultants
state: Florida
city: Ft. Myers
country: United States
facility: Retina Consultants of Southwest Florida
state: Florida
city: Ft. Myers
country: United States
facility: Retina Health Center
state: Florida
city: Margate
country: United States
facility: Retina Associates of South Florida
state: Florida
city: Miami
country: United States
facility: Bascom Palmer Eye Institute
state: Florida
city: Orlando
country: United States
facility: Central Florida Retina
state: Florida
city: Palm Beach Gardens
country: United States
facility: Retina Care Specialists
state: Florida
city: Palm Beach Gardens
country: United States
facility: Bascom Palmer Eye Institute
state: Florida
city: Sarasota
country: United States
facility: Ophthalmic Consultants
state: Florida
city: Tallahassee
country: United States
facility: Southern Vitreoretinal Associates PA
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Indianapolis
country: United States
facility: Thomas A. Ciulla, MD, PC
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Annapolis
country: United States
facility: Retina Associates PC
state: Maryland
city: Boston
country: United States
facility: New England Eye Center
state: Massachusetts
city: Boston
country: United States
facility: Center for Eye Research
state: Massachusetts
city: West Springfield
country: United States
facility: New England Retina Consultants
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Grand Rapids
country: United States
facility: Associated Retinal Consultants
state: Michigan
city: Royal Oak
country: United States
facility: Associated Retinal Consultants, P.C.
state: Michigan
city: Southfield
country: United States
facility: Retina Consultants of Michigan
state: Michigan
city: Florissant
country: United States
facility: Retina Associates of St. Louis
state: Missouri
city: St. Louis
country: United States
facility: St. Louis University Eye Institute
state: Missouri
city: Lawrenceville
country: United States
facility: Delaware Valley Retina Associates
state: New Jersey
city: Albany
country: United States
facility: Lions Eye Institute
state: New York
city: Rockville Centre
country: United States
facility: Ophthalmic Consultants of Long Island
state: New York
city: Asheville
country: United States
facility: Western Carolina Retinal Associates, PA
state: North Carolina
city: Charlotte
country: United States
facility: Southeast Clinical Research
state: North Carolina
city: Durham
country: United States
facility: Duke Univ Medical Center/Duke Eye Center
state: North Carolina
city: Beachwood
country: United States
facility: Retina Associates of Cleveland
state: Ohio
city: Cincinnati
country: United States
facility: Flavio Company
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation/Cole Eye Institute
state: Ohio
city: Columbus
country: United States
facility: Midwest Retina
state: Ohio
city: Toledo
country: United States
facility: Retina Vitreous Associates
state: Ohio
city: Oklahoma City
country: United States
facility: Retinal Associates of Oklahoma
state: Oklahoma
city: Ashland
country: United States
facility: Retina & Vitreous Center of So. Oregon
state: Oregon
city: Camp Hill
country: United States
facility: Pennsylvania Retina Specialists
state: Pennsylvania
city: Philadelphia
country: United States
facility: Wills Eye Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Retina Consultants of Charleston
state: South Carolina
city: Columbia
country: United States
facility: Palmetto Retina Center
state: South Carolina
city: Rapid City
country: United States
facility: BH Regional Eye Institute
state: South Dakota
city: Knoxville
country: United States
facility: Southeastern Retina Associates, P.C.
state: Tennessee
city: Nashville
country: United States
facility: Retina Vitreous Associates
state: Tennessee
city: Austin
country: United States
facility: Austin Retina Associates
state: Texas
city: Austin
country: United States
facility: Brian Berger, MD P.A.
state: Texas
city: Desoto
country: United States
facility: Retina Specialists
state: Texas
city: Galveston
country: United States
facility: UTMB
state: Texas
city: Houston
country: United States
facility: Vitreoretinal Consultants
state: Texas
city: McAllen
country: United States
facility: Valley Retina Institute, P.A.
state: Texas
city: San Antonio
country: United States
facility: Univ of Texas Health Science Center
state: Texas
city: San Antonio
country: United States
facility: Medical Center Ophthalmology
state: Texas
city: Salt Lake City
country: United States
facility: Rocky Mountain Retina Consultants
state: Utah
city: Salt Lake City
country: United States
facility: John Moran Eye Center/Univ of Utah
state: Utah
city: Fairfax
country: United States
facility: Retina Group of Washington
state: Virginia
city: Seattle
country: United States
facility: Vitreoretinal Associates
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: East Melbourne
country: Australia
facility: University of Melbourne, Department of Ophthalmology
city: Parramatta
country: Australia
facility: Marsden Eye Research Pty Ltd
city: Sydney
country: Australia
facility: Save Sight Institute
city: Westmead
country: Australia
facility: Westmead Hospital
city: Praha 10
country: Czech Republic
facility: Onci klinika FNKV
city: Creteil Cedex
country: France
facility: Clinique d'Ophtalmologie
city: Marseille
country: France
facility: Clinique Monticelli
city: Paris Cedex 10
country: France
facility: HÃ´pital LariboisiÃ¨re
city: Bonn
country: Germany
facility: UniversitÃ¤tsklinikum Bonn
city: Koln
country: Germany
facility: Universitatskliniken Koln
city: Leipzig
country: Germany
facility: UniversitÃ¤tsklinikum Leipzig
city: Budapest
country: Hungary
facility: Semmelweis University, 1st Ophthalmological Department
Study officials:
References:
citation: 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. doi: 10.1056/NEJMoa062655.
citation: Kaiser PK, Brown DM, Zhang K, Hudson HL, Holz FG, Shapiro H, Schneider S, Acharya NR. Ranibizumab for predominantly classic neovascular age-related macular degeneration: subgroup analysis of first-year ANCHOR results. Am J Ophthalmol. 2007 Dec;144(6):850-857. doi: 10.1016/j.ajo.2007.08.012. Epub 2007 Oct 22.
citation: Brown DM, Michels M, Kaiser PK, Heier JS, Sy JP, Ianchulev T; ANCHOR Study Group. Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: Two-year results of the ANCHOR study. Ophthalmology. 2009 Jan;116(1):57-65.e5. doi: 10.1016/j.ophtha.2008.10.018.
citation: Suner IJ, Kokame GT, Yu E, Ward J, Dolan C, Bressler NM. Responsiveness of NEI VFQ-25 to changes in visual acuity in neovascular AMD: validation studies from two phase 3 clinical trials. Invest Ophthalmol Vis Sci. 2009 Aug;50(8):3629-35. doi: 10.1167/iovs.08-3225. Epub 2009 Feb 28.
citation: Bressler NM, Chang TS, Fine JT, Dolan CM, Ward J; Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in Age-Related Macular Degeneration (ANCHOR) Research Group. Improved vision-related function after ranibizumab vs photodynamic therapy: a randomized clinical trial. Arch Ophthalmol. 2009 Jan;127(1):13-21. doi: 10.1001/archophthalmol.2008.562.
citation: Thach AB, Yau L, Hoang C, Tuomi L. Time to clinically significant visual acuity gains after ranibizumab treatment for retinal vein occlusion: BRAVO and CRUISE trials. Ophthalmology. 2014 May;121(5):1059-66. doi: 10.1016/j.ophtha.2013.11.022. Epub 2014 Jan 11.
citation: Weinberg DV, Shapiro H, Ehrlich JS. Ranibizumab treatment outcomes in phakic versus pseudophakic eyes: an individual patient data analysis of 2 phase 3 trials. Ophthalmology. 2013 Jun;120(6):1278-82. doi: 10.1016/j.ophtha.2012.11.042. Epub 2013 Feb 28.
citation: Bressler NM, Chang TS, Varma R, Suner I, Lee P, Dolan CM, Ward J, Ianchulev T, Fine J. Driving ability reported by neovascular age-related macular degeneration patients after treatment with ranibizumab. Ophthalmology. 2013 Jan;120(1):160-8. doi: 10.1016/j.ophtha.2012.07.027. Epub 2012 Sep 23.
citation: Rosenfeld PJ, Shapiro H, Ehrlich JS, Wong P; MARINA and ANCHOR Study Groups. Cataract surgery in ranibizumab-treated patients with neovascular age-related macular degeneration from the phase 3 ANCHOR and MARINA trials. Am J Ophthalmol. 2011 Nov;152(5):793-8. doi: 10.1016/j.ajo.2011.04.025. Epub 2011 Jul 26.
citation: Rosenfeld PJ, Shapiro H, Tuomi L, Webster M, Elledge J, Blodi B; MARINA and ANCHOR Study Groups. Characteristics of patients losing vision after 2 years of monthly dosing in the phase III ranibizumab clinical trials. Ophthalmology. 2011 Mar;118(3):523-30. doi: 10.1016/j.ophtha.2010.07.011.
citation: Barbazetto IA, Saroj N, Shapiro H, Wong P, Ho AC, Freund KB. Incidence of new choroidal neovascularization in fellow eyes of patients treated in the MARINA and ANCHOR trials. Am J Ophthalmol. 2010 Jun;149(6):939-946.e1. doi: 10.1016/j.ajo.2010.01.007. Epub 2010 Apr 8.
citation: Bressler NM, Chang TS, Suner IJ, Fine JT, Dolan CM, Ward J, Ianchulev T; MARINA and ANCHOR Research Groups. Vision-related function after ranibizumab treatment by better- or worse-seeing eye: clinical trial results from MARINA and ANCHOR. Ophthalmology. 2010 Apr;117(4):747-56.e4. doi: 10.1016/j.ophtha.2009.09.002. Epub 2010 Mar 2.