Verteporfin Photodynamic Therapy Administered in Conjunction With Ranibizumab in Patients With Subfoveal Choroidal Neovascularization Secondary to Age-related Macular Degeneration (AMD)

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Primary Purpose

Status

Terminated

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Verteporfin Photodynamic Therapy

Ranibizumab

Placebo

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

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Other protocol-defined inclusion/exclusion criteria may apply

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Verteporfin + Ranibizumab

Ranibizumab Monotherapy

Arm Description

Verteporfin (6 mg/m^2) photodynamic therapy (PDT) and ranibizumab (0.5 mg). Patients received three consecutive monthly ranibizumab injections starting on Day 1, and then as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin PDT 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 CNV leakage assessed by fluorescein angiography (FA).

Patients received three consecutive monthly ranibizumab injections starting on Day 1 and then as needed from Month 3 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. 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 CNV leakage assessed by fluorescein angiography (FA).

Outcomes

Primary Outcome Measures

Change From Baseline in Best-corrected Visual Acuity (BCVA) 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 Participants 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

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

The proportion of patients with leakage of the study eye was assessed at the Central Reading Center (CRC) using Fluorescein angiography (FA).

Mean Change in Total Area of Leakage (Observed) of the Study Eye at Month 12

Fluorescein angiography (FA) was used to assess the mean change of leakage of the study eye at the Central Reading Center (CRC). A negative change from baseline indicates improvement, ie, less leakage.

Mean Change in Central Retinal Thickness of the Study Eye at Month 12

Optical coherence tomography (OCT) was used to assess the mean change in retinal thickness of the study eye at the Central Reading Center (CRC). A negative change from baseline indicates improvement, ie, less thickness.

Full Information

NCT ID

NCT00433017

First Posted

February 8, 2007

Last Updated

April 18, 2011

Sponsor

Novartis

1. Study Identification

Unique Protocol Identification Number

NCT00433017

Brief Title

Verteporfin Photodynamic Therapy Administered in Conjunction With Ranibizumab in Patients With Subfoveal Choroidal Neovascularization Secondary to Age-related Macular Degeneration (AMD)

Official Title

24-month Randomized, Double-masked, Controlled, Multicenter, Phase II 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 AMD.

Study Type

Interventional

2. Study Status

Record Verification Date

April 2011

Overall Recruitment Status

Terminated

Why Stopped

Study was terminated based on the results of analyses performed as planned at Month 12.

Study Start Date

May 2007 (undefined)

Primary Completion Date

July 2009 (Actual)

Study Completion Date

July 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Novartis

4. Oversight

5. Study Description

Brief Summary

This study will evaluate the effect of combination therapy with verteporfin photodynamic therapy and ranibizumab on visual acuity 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 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

255 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Verteporfin + Ranibizumab

Arm Type

Experimental

Arm Description

Verteporfin (6 mg/m^2) photodynamic therapy (PDT) and ranibizumab (0.5 mg). Patients received three consecutive monthly ranibizumab injections starting on Day 1, and then as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin PDT 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 CNV leakage assessed by fluorescein angiography (FA).

Arm Title

Ranibizumab Monotherapy

Arm Type

Active Comparator

Arm Description

Patients received three consecutive monthly ranibizumab injections starting on Day 1 and then as needed from Month 3 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. 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 CNV leakage assessed by fluorescein angiography (FA).

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 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 (0.05 mL of 10 mg/mL solution for injection) administered as an intravitreal injection

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

As a placebo for verteporfin photodynamic therapy (for masking purposes), 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.

Primary Outcome Measure Information:

Title

Change From Baseline in Best-corrected Visual Acuity (BCVA) 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 Participants 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 to Month 11

Secondary Outcome Measure Information:

Title

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

Description

The proportion 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

Mean Change in Total Area of Leakage (Observed) of the Study Eye at Month 12

Description

Fluorescein angiography (FA) was used to assess the mean change of leakage of the study eye at the Central Reading Center (CRC). A negative change from baseline indicates improvement, ie, less leakage.

Time Frame

Baseline and Month 12

Title

Mean Change in Central Retinal Thickness of the Study Eye at Month 12

Description

Optical coherence tomography (OCT) was used to assess the mean change in retinal thickness of the study eye at the Central Reading Center (CRC). A negative change from baseline indicates improvement, ie, less thickness.

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 choriodal neovascularization (CNV) due to age-related macular degeneration (AMD) Exclusion Criteria: Choriodal 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

Wien

Country

Austria

Facility Name

Novartis Investigative site

City

Antwerpen

Country

Belgium

Facility Name

Novartis Investigative site

City

Aalborg

Country

Denmark

Facility Name

Novartis Investigative site

City

Creteil

Country

France

Facility Name

Novartis Investigative site

City

Regensburg

Country

Germany

Facility Name

Novartis Investigative site

City

Budapest

Country

Hungary

Facility Name

Novartis Investigative site

City

Firenze

Country

Italy

Facility Name

Novartis Investigative site

City

Rotterdam

Country

Netherlands

Facility Name

Novartis Investigative site

City

Warszawa

Country

Poland

Facility Name

Novartis Investigative site

City

Madrid

Country

Spain

Facility Name

Novartis Investigative site

City

Geneve

Country

Switzerland

Facility Name

Novartis Investigative site

City

Manchester

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

25079064

Citation

Ritter M, Simader C, Bolz M, Deak GG, Mayr-Sponer U, Sayegh R, Kundi M, Schmidt-Erfurth UM. Intraretinal cysts are the most relevant prognostic biomarker in neovascular age-related macular degeneration independent of the therapeutic strategy. Br J Ophthalmol. 2014 Dec;98(12):1629-35. doi: 10.1136/bjophthalmol-2014-305186. Epub 2014 Jul 30.

Results Reference

derived

PubMed Identifier

22424834

Citation

Larsen M, Schmidt-Erfurth U, Lanzetta P, Wolf S, Simader C, Tokaji E, Pilz S, Weisberger A; MONT BLANC Study Group. Verteporfin plus ranibizumab for choroidal neovascularization in age-related macular degeneration: twelve-month MONT BLANC study results. Ophthalmology. 2012 May;119(5):992-1000. doi: 10.1016/j.ophtha.2012.02.002. Epub 2012 Mar 17.

Results Reference

derived

Macular Degeneration, Choroidal Neovascularization

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial