Efficacy/Safety of Verteporfin Photodynamic Therapy and Ranibizumab Compared With Ranibizumab in Patients With Subfoveal Choroidal Neovascularization - Full Text View

Sponsor:	Novartis
Information provided by:	Novartis
ClinicalTrials.gov Identifier:	NCT00436553

Purpose

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.

Condition	Intervention	Phase
Macular Degeneration Choroidal Neovascularization	Drug: Verteporfin Photodynamic Therapy Drug: Ranibizumab Drug: Verteporfin Placebo Drug: Ranibizumab Placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
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

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 Novartis:

Primary Outcome Measures:

Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) of the Study Eye at Month 12 [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
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 [ Time Frame: Month 2 up to Month 11 ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
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 [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
Optical coherence tomography was performed in the study eyes and the evaluations of the images were performed by the central reading center.

Enrollment:	321
Study Start Date:	February 2007
Study Completion Date:	October 2009
Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Verteporfin With Standard Fluence Rate Plus Ranibizumab 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.	Drug: Verteporfin Photodynamic Therapy 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. Other Name: Visudyne Drug: Ranibizumab Ranibizumab 0.5 mg administered as an intravitreal injection. Other Name: Lucentis Drug: Ranibizumab Placebo 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.
Active Comparator: Ranibizumab Monotherapy 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).	Drug: Ranibizumab Ranibizumab 0.5 mg administered as an intravitreal injection. Other Name: Lucentis Drug: Verteporfin Placebo 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.
Experimental: Verteporfin With Reduced Fluence Rate Plus Ranibizumab 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.	Drug: Verteporfin Photodynamic Therapy 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. Other Name: Visudyne Drug: Ranibizumab Ranibizumab 0.5 mg administered as an intravitreal injection. Other Name: Lucentis Drug: Ranibizumab Placebo 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.

Eligibility

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00436553

Show 43 Study Locations

Sponsors and Collaborators

Novartis

Investigators

Study Chair:

Novartis

More Information

No publications provided

Responsible Party:	External Affairs, Novartis
ClinicalTrials.gov Identifier:	NCT00436553 History of Changes
Other Study ID Numbers:	CBPD952A2308
Study First Received:	February 16, 2007
Results First Received:	January 6, 2011
Last Updated:	March 23, 2011
Health Authority:	United States: Food and Drug Administration; Canada: Health Canada

Keywords provided by Novartis:

Age-related macular degeneration; AMD
choroidal neovascularization
verteporfin
ranibizumab

Additional relevant MeSH terms:

Macular Degeneration
Neovascularization, Pathologic
Choroidal Neovascularization
Retinal Degeneration
Retinal Diseases
Eye Diseases
Metaplasia
Pathologic Processes
Choroid Diseases

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

ClinicalTrials.gov processed this record on February 09, 2012