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

NCT00436553 | Completed Phase 3 Results

• 1 other identifier: CBPD952A2308
• Study Type: interventional
• Target: 321
• Locations: 2 countries
• Sites: 43

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.

Conditions

Macular Degeneration; Choroidal Neovascularization

Keywords

Age-related macular degeneration; AMD; choroidal neovascularization; verteporfin; ranibizumab

Outcome Measures

Primary Outcomes (2)

• 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.

  Baseline and Month 12

• 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.

  Month 2 up to Month 11

Secondary Outcomes (3)

• Change From Baseline in Total Area of Leakage of the Study Eye at Month 12

  Baseline and Month 12

• Percentage of Patients With Fluorescein Leakage in the Study Eye at Month 12

  Month 12

• Change From Baseline in Central Retinal Thickness at Month 12

  Baseline and Month 12

Study Arms (3)

Verteporfin With Standard Fluence Rate Plus Ranibizumab

EXPERIMENTAL

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; Drug: Ranibizumab; Drug: Ranibizumab Placebo

Ranibizumab Monotherapy

ACTIVE COMPARATOR

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; Drug: Verteporfin Placebo

Verteporfin With Reduced Fluence Rate Plus Ranibizumab

EXPERIMENTAL

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; Drug: Ranibizumab; Drug: Ranibizumab Placebo

Interventions

Verteporfin Photodynamic Therapy DRUG

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.

Also known as: Visudyne

Verteporfin With Reduced Fluence Rate Plus Ranibizumab; Verteporfin With Standard Fluence Rate Plus Ranibizumab

Ranibizumab DRUG

Ranibizumab 0.5 mg administered as an intravitreal injection.

Also known as: Lucentis

Ranibizumab Monotherapy; Verteporfin With Reduced Fluence Rate Plus Ranibizumab; Verteporfin With Standard Fluence Rate Plus Ranibizumab

Verteporfin Placebo DRUG

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.

Ranibizumab Monotherapy

Ranibizumab Placebo DRUG

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.

Verteporfin With Reduced Fluence Rate Plus Ranibizumab; Verteporfin With Standard Fluence Rate Plus Ranibizumab

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects of either gender age 50 years or older
• Subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD)

You may not qualify if:

• Choroidal neovascularization due to causes other than AMD
• Prior treatment for neovascular AMD in the study eye

Sponsors & Collaborators

• Novartis: lead

Study Sites (43)

Novartis Investigative Site

Tucson, Arizona, 85704, United States

Location

Novartis Investigative Site

Beverly Hills, California, 90211, United States

Location

Novartis Investigative Site

Oakland, California, 94609, United States

Location

Novartis Investigative Site

Pasadena, California, 91105-3153, United States

Location

Novartis Investigative Site

Sacramento, California, 95819, United States

Location

West Coast Retina Medical Group Inc. - 185 Berry St. Suite 130

San Francisco, California, 94107, United States

Location

Novartis Investigative Site

Santa Ana, California, 92705, United States

Location

Novartis Investigative Site

Denver, Colorado, 80210, United States

Location

Novartis Investigative Site

‘Aiea, Hawaii, 96701, United States

Location

Novartis Investigative Site

Iowa City, Iowa, 52242, United States

Location

Novartis Investigative Site

Wichita, Kansas, 67214, United States

Location

Novartis Investigative Site

Lexington, Kentucky, 40509, United States

Location

Novartis Investigative Site

Paducah, Kentucky, 42001, United States

Location

Novartis Investigative Site

Baltimore, Maryland, 21205, United States

Location

Novartis Investigative Site

Grand Rapids, Michigan, 49252, United States

Location

Novartis Investigative SIte

Royal Oak, Michigan, 48073, United States

Location

Novartis Investigative Site

Williamsburg, Michigan, 49690, United States

Location

Novartis Investigative Site

Independence, Missouri, 64055, United States

Location

Novartis Investigative Site

St Louis, Missouri, 63110, United States

Location

Novartis Investigative Site

Toms River, New Jersey, 08755, United States

Location

Novartis Investigative Site

Lynbrook, New York, 11563, United States

Location

Novartis Investigative Site

Rochester, New York, 14620, United States

Location

Novartis Investigative Site

Beachwood, Ohio, 44122, United States

Location

Novartis Investigative Site

Cincinnati, Ohio, 45242, United States

Location

Novartis Investigative Site

Cleveland, Ohio, 44195, United States

Location

Novartis Investigative Site

Pittsburgh, Pennsylvania, 15213, United States

Location

Novartis Investigative Site

West Mifflin, Pennsylvania, 15122, United States

Location

Novartis Investigative Site

West Columbia, South Carolina, 29169, United States

Location

Novartis Investigative Site

Rapid City, South Dakota, 57701, United States

Location

Novartis Investigative Site

Kingsport, Tennessee, 37660, United States

Location

Novartis Investigative Site

Knoxville, Tennessee, 37909, United States

Location

Novartis Investigative Site

Austin, Texas, 78705, United States

Location

Novartis Investigative Site

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

Fairfax, Virginia, 22031, United States

Location

Novartis Investigative Site

Richmond, Virginia, 23226, United States

Location

Novartis Investigative Site

Milwaukee, Wisconsin, 53226, United States

Location

Novartis Investigative Site

Edmonton, Alberta, T5H OX5, Canada

Location

Novartis Investigative Site

Vancouver, British Columbia, V5Z 3N9, Canada

Location

Novartis Investigative Site

Halifax, Nova Scotia, B3H 2Y6, Canada

Location

Ivey Eye Institute, Dr. Thomas Sheidow

London, Ontario, N6A 4G5, Canada

Location

Novartis Investigative Site

London, Ontario, N6A 4G5, Canada

Location

Novartis Investigative Site

Ottawa, Ontario, KIH 8L6, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H2L 4MI, Canada

Location

Related Publications (1)

• 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.

  PMID: 22444829 DERIVED

MeSH Terms

Conditions

Macular Degeneration; Choroidal Neovascularization

Interventions

Verteporfin; Ranibizumab

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases; Choroid Diseases; Uveal Diseases; Neovascularization, Pathologic; Metaplasia; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Porphyrins; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Macrocyclic Compounds; Polycyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Shorten the study duration from 24 months to 12 months based on results of the European combination study MONT BLANC (CBPD952A2309).

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862 778-8300

Study Officials

• Novartis

  Novartis

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: February 16, 2007
• First Posted: February 19, 2007
• Study Start: February 1, 2007
• Primary Completion: October 1, 2009
• Study Completion: October 1, 2009
• Last Updated: April 19, 2011
• Results First Posted: April 19, 2011

Record last verified: 2011-03

Locations

CA (7); US (36)