Back to resultsEfficacy/Safety of Verteporfin Photodynamic Therapy and Ranibizumab Compared With Ranibizumab in Patients With Subfoveal Choroidal Neovascularization
Primary Purpose
Macular Degeneration, Choroidal Neovascularization
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Verteporfin Photodynamic Therapy
Ranibizumab
Verteporfin Placebo
Ranibizumab Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Macular Degeneration focused on measuring Age-related macular degeneration; AMD, choroidal neovascularization, verteporfin, ranibizumab
Eligibility Criteria
Inclusion Criteria:
- Subjects of either gender age 50 years or older
- Subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD)
Exclusion Criteria:
- Choroidal neovascularization due to causes other than AMD
- Prior treatment for neovascular AMD in the study eye
Other protocol-defined inclusion/exclusion criteria may apply
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- West Coast Retina Medical Group Inc. - 185 Berry St. Suite 130
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative SIte
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Ivey Eye Institute, Dr. Thomas Sheidow
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Experimental
Arm Label
Verteporfin With Standard Fluence Rate Plus Ranibizumab
Ranibizumab Monotherapy
Verteporfin With Reduced Fluence Rate Plus Ranibizumab
Arm Description
Patients received three consecutive monthly ranibizumab injections on Day 1 and at Months 1 and 2, and thereafter as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin photodynamic therapy (PDT) with standard fluence (SF) rate on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. From month 3 onward, retreatments were determined based on study-specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA). Patients received sham intravitreal injections for the first 12 months if retreatment with ranibizumab was not warranted based on the retreatment criteria.
Patients received monthly ranibizumab injections for 12 months and thereafter as needed based on the retreatment criteria. These patients were also administered verteporfin placebo infusion with sham PDT on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. Retreatments were determined based on study specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA).
Patients received three consecutive monthly ranibizumab injections on Day 1 and at Months 1 and 2, and thereafter as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin PDT with reduced fluence (RF) rate on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. From month 3 onward, retreatments were determined based on study-specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA). Patients received sham intravitreal injections for the first 12 months if retreatment with ranibizumab was not warranted based on the retreatment criteria.
Outcomes
Primary Outcome Measures
Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) of the Study Eye at Month 12
BCVA score was based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters. An ETDRS visual acuity score of 85 is approximately 20/20. An increase in the VA score indicates improvement in visual acuity.
Percent of Patients With a Treatment-free Interval of at Least 3 Months Following the Month 2 Visit
The number of patients with a ranibizumab treatment-free interval, ie, no active ranibizumab treatments for at least 3 months duration (at least 2 consecutive monthly visits), anytime following the Month 2 ranibizumab treatment. Only active ranibizumab treatments were considered.
Secondary Outcome Measures
Change From Baseline in Total Area of Leakage of the Study Eye at Month 12
Total area of leakage of the study eye was assessed at the Central Reading Center (CRC) using Fluorescein angiography (FA).
Percentage of Patients With Fluorescein Leakage in the Study Eye at Month 12
The percentage of patients with leakage of the study eye was assessed at the Central Reading Center (CRC) using Fluorescein angiography (FA).
Change From Baseline in Central Retinal Thickness at Month 12
Optical coherence tomography was performed in the study eyes and the evaluations of the images were performed by the central reading center.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00436553
Brief Title
Efficacy/Safety of Verteporfin Photodynamic Therapy and Ranibizumab Compared With Ranibizumab in Patients With Subfoveal Choroidal Neovascularization
Official Title
A 24-month Randomized, Double-masked, Controlled, Multicenter, Phase IIIB Study Assessing Safety and Efficacy of Verteporfin Photodynamic Therapy Administered in Conjunction With Ranibizumab Versus Ranibizumab Monotherapy in Patients With Subfoveal Choroidal Neovascularization Secondary to Age-related Macular Degeneration
Study Type
Interventional
2. Study Status
Record Verification Date
March 2011
Overall Recruitment Status
Completed
Study Start Date
February 2007 (undefined)
Primary Completion Date
October 2009 (Actual)
Study Completion Date
October 2009 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Novartis
4. Oversight
5. Study Description
Brief Summary
This study evaluated the effect of combination therapy with verteporfin photodynamic therapy and ranibizumab on visual acuity and anatomic outcomes compared to ranibizumab monotherapy and the durability of response observed in patients with choroidal neovascularization secondary to age-related macular degeneration.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Macular Degeneration, Choroidal Neovascularization
Keywords
Age-related macular degeneration; AMD, choroidal neovascularization, verteporfin, ranibizumab
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
321 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Verteporfin With Standard Fluence Rate Plus Ranibizumab
Arm Type
Experimental
Arm Description
Patients received three consecutive monthly ranibizumab injections on Day 1 and at Months 1 and 2, and thereafter as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin photodynamic therapy (PDT) with standard fluence (SF) rate on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. From month 3 onward, retreatments were determined based on study-specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA). Patients received sham intravitreal injections for the first 12 months if retreatment with ranibizumab was not warranted based on the retreatment criteria.
Arm Title
Ranibizumab Monotherapy
Arm Type
Active Comparator
Arm Description
Patients received monthly ranibizumab injections for 12 months and thereafter as needed based on the retreatment criteria. These patients were also administered verteporfin placebo infusion with sham PDT on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. Retreatments were determined based on study specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA).
Arm Title
Verteporfin With Reduced Fluence Rate Plus Ranibizumab
Arm Type
Experimental
Arm Description
Patients received three consecutive monthly ranibizumab injections on Day 1 and at Months 1 and 2, and thereafter as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin PDT with reduced fluence (RF) rate on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. From month 3 onward, retreatments were determined based on study-specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA). Patients received sham intravitreal injections for the first 12 months if retreatment with ranibizumab was not warranted based on the retreatment criteria.
Intervention Type
Drug
Intervention Name(s)
Verteporfin Photodynamic Therapy
Other Intervention Name(s)
Visudyne
Intervention Description
After a 10-minute intravenous infusion of verteporfin at a dose of 6 mg/m^2 body surface area, verteporfin was activated by light application of 50 J/cm^2 (Standard Fluence rate) or 25 J/cm^2 (Reduced Fluence rate) to the study eye, begun 15 minutes after the start of the infusion.
Intervention Type
Drug
Intervention Name(s)
Ranibizumab
Other Intervention Name(s)
Lucentis
Intervention Description
Ranibizumab 0.5 mg administered as an intravitreal injection.
Intervention Type
Drug
Intervention Name(s)
Verteporfin Placebo
Intervention Description
To maintain masking, as a placebo for verteporfin photodynamic therapy, patients were administered a 10-minute intravenous infusion of 5% dextrose solution, followed by light application of 50 J/cm^2 to the study eye, begun 15 minutes after the start of infusion.
Intervention Type
Drug
Intervention Name(s)
Ranibizumab Placebo
Intervention Description
To maintain masking, patients in the combination groups received sham intravitreal injections whenever retreatment with active Ranibizumab was not warranted based on the retreatment algorithm.
Primary Outcome Measure Information:
Title
Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) of the Study Eye at Month 12
Description
BCVA score was based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters. An ETDRS visual acuity score of 85 is approximately 20/20. An increase in the VA score indicates improvement in visual acuity.
Time Frame
Baseline and Month 12
Title
Percent of Patients With a Treatment-free Interval of at Least 3 Months Following the Month 2 Visit
Description
The number of patients with a ranibizumab treatment-free interval, ie, no active ranibizumab treatments for at least 3 months duration (at least 2 consecutive monthly visits), anytime following the Month 2 ranibizumab treatment. Only active ranibizumab treatments were considered.
Time Frame
Month 2 up to Month 11
Secondary Outcome Measure Information:
Title
Change From Baseline in Total Area of Leakage of the Study Eye at Month 12
Description
Total area of leakage of the study eye was assessed at the Central Reading Center (CRC) using Fluorescein angiography (FA).
Time Frame
Baseline and Month 12
Title
Percentage of Patients With Fluorescein Leakage in the Study Eye at Month 12
Description
The percentage of patients with leakage of the study eye was assessed at the Central Reading Center (CRC) using Fluorescein angiography (FA).
Time Frame
Month 12
Title
Change From Baseline in Central Retinal Thickness at Month 12
Description
Optical coherence tomography was performed in the study eyes and the evaluations of the images were performed by the central reading center.
Time Frame
Baseline and Month 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects of either gender age 50 years or older
Subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD)
Exclusion Criteria:
Choroidal neovascularization due to causes other than AMD
Prior treatment for neovascular AMD in the study eye
Other protocol-defined inclusion/exclusion criteria may apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis
Organizational Affiliation
Novartis
Official's Role
Study Chair
Facility Information:
Facility Name
Novartis Investigative Site
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85704
Country
United States
Facility Name
Novartis Investigative Site
City
Beverly Hills
State/Province
California
ZIP/Postal Code
90211
Country
United States
Facility Name
Novartis Investigative Site
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Facility Name
Novartis Investigative Site
City
Pasadena
State/Province
California
ZIP/Postal Code
91105-3153
Country
United States
Facility Name
Novartis Investigative Site
City
Sacramento
State/Province
California
ZIP/Postal Code
95819
Country
United States
Facility Name
West Coast Retina Medical Group Inc. - 185 Berry St. Suite 130
City
San Francisco
State/Province
California
ZIP/Postal Code
94107
Country
United States
Facility Name
Novartis Investigative Site
City
Santa Ana
State/Province
California
ZIP/Postal Code
92705
Country
United States
Facility Name
Novartis Investigative Site
City
Denver
State/Province
Colorado
ZIP/Postal Code
80210
Country
United States
Facility Name
Novartis Investigative Site
City
Aiea
State/Province
Hawaii
ZIP/Postal Code
96701
Country
United States
Facility Name
Novartis Investigative Site
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Novartis Investigative Site
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214
Country
United States
Facility Name
Novartis Investigative Site
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40509
Country
United States
Facility Name
Novartis Investigative Site
City
Paducah
State/Province
Kentucky
ZIP/Postal Code
42001
Country
United States
Facility Name
Novartis Investigative Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
Novartis Investigative Site
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49252
Country
United States
Facility Name
Novartis Investigative SIte
City
Royal Oak
State/Province
Michigan
ZIP/Postal Code
48073
Country
United States
Facility Name
Novartis Investigative Site
City
Williamsburg
State/Province
Michigan
ZIP/Postal Code
49690
Country
United States
Facility Name
Novartis Investigative Site
City
Independence
State/Province
Missouri
ZIP/Postal Code
64055
Country
United States
Facility Name
Novartis Investigative Site
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Novartis Investigative Site
City
Toms River
State/Province
New Jersey
ZIP/Postal Code
08755
Country
United States
Facility Name
Novartis Investigative Site
City
Lynbrook
State/Province
New York
ZIP/Postal Code
11563
Country
United States
Facility Name
Novartis Investigative Site
City
Rochester
State/Province
New York
ZIP/Postal Code
14620
Country
United States
Facility Name
Novartis Investigative Site
City
Beachwood
State/Province
Ohio
ZIP/Postal Code
44122
Country
United States
Facility Name
Novartis Investigative Site
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45242
Country
United States
Facility Name
Novartis Investigative Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Novartis Investigative Site
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Novartis Investigative Site
City
West Mifflin
State/Province
Pennsylvania
ZIP/Postal Code
15122
Country
United States
Facility Name
Novartis Investigative Site
City
West Columbia
State/Province
South Carolina
ZIP/Postal Code
29169
Country
United States
Facility Name
Novartis Investigative Site
City
Rapid City
State/Province
South Dakota
ZIP/Postal Code
57701
Country
United States
Facility Name
Novartis Investigative Site
City
Kingsport
State/Province
Tennessee
ZIP/Postal Code
37660
Country
United States
Facility Name
Novartis Investigative Site
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37909
Country
United States
Facility Name
Novartis Investigative Site
City
Austin
State/Province
Texas
ZIP/Postal Code
78705
Country
United States
Facility Name
Novartis Investigative Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Novartis Investigative Site
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
Novartis Investigative Site
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23226
Country
United States
Facility Name
Novartis Investigative Site
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Novartis Investigative Site
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T5H OX5
Country
Canada
Facility Name
Novartis Investigative Site
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 3N9
Country
Canada
Facility Name
Novartis Investigative Site
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 2Y6
Country
Canada
Facility Name
Ivey Eye Institute, Dr. Thomas Sheidow
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 4G5
Country
Canada
Facility Name
Novartis Investigative Site
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 4G5
Country
Canada
Facility Name
Novartis Investigative Site
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
KIH 8L6
Country
Canada
Facility Name
Novartis Investigative Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2L 4MI
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
22444829
Citation
Kaiser PK, Boyer DS, Cruess AF, Slakter JS, Pilz S, Weisberger A; DENALI Study Group. Verteporfin plus ranibizumab for choroidal neovascularization in age-related macular degeneration: twelve-month results of the DENALI study. Ophthalmology. 2012 May;119(5):1001-10. doi: 10.1016/j.ophtha.2012.02.003. Epub 2012 Mar 22.
Results Reference
derived
Learn more about this trial
Efficacy/Safety of Verteporfin Photodynamic Therapy and Ranibizumab Compared With Ranibizumab in Patients With Subfoveal Choroidal Neovascularization
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