Polypoidal Choroidal Vasculopathy
Conditions
Keywords
Polypoidal choroidal vasculopathy, PCV, Age-related macular degeneration (AMD) variant, vision, polyps, indocyanine green angiography, verteporfin, ranibizumab, photodynamic therapy
Brief summary
This study aims to compare the efficacy of ranibizumab and verteporfin PDT combination treatment and verteporfin PDT monotherapy vs.ranibizumab monotherapy alone in achieving complete regression of polyps in patients with symptomatic macular polypoidal choroidal vasculopathy.
Interventions
After a 10-minute intravenous infusion of verteporfin at a dose of 6 mg/m\^2 body surface area, light application of 50 J/cm\^2 to the study eye was begun 15 minutes after the start of infusion.
DRUGRanibizumab
Ranibizumab at dose of 0.5 mg administered as an intravitreal injection.
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must give written informed consent before any assessment is performed. * Male or Female patients ≥18 yrs of age * Patients willing and able to comply with all study procedures Inclusion criteria for study eye: * BCVA letter score between 73-24 (approximately 20/40 to 20/320 Snellen equivalent) using ETDRS visual acuity chart measured at 4 meters * PCV diagnosis confirmed by Central Reading Center * Greatest Linear Dimension (GLD) of the total lesion area \< 5400 µm (\ 9 Macular Photocoagulation Study Disc Areas)
Exclusion criteria
* Women of child-bearing potential who are not using one or more reliable contraception methods * Pregnant or nursing (lactating) women * History of hypersensitivity or allergy to fluorescein or indocyanine green (ICG), clinically significant drug allergy or known hypersensitivity to therapeutic or diagnostic protein products, or to any of the study drugs or their components * Patient with history of porphyria * Systemic medications known to be toxic to the lens, retina, or optic nerve * History of which might affect the interpretation of the results of the study, or renders the patient at high risk from treatment complications * Use of other investigational drugs within 30 days of randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Complete Regression (CR) of Polyps Measured by Indocyanine Green Angiography (ICGA) | Month 6 | Indocyanine green angiography (ICGA) assessments were performed using the Heidelberg Retinal Angiography 2 (HRA2) machine to measure the Total Lesion Area and the degree of polyp regression. Complete regression was defined as no polyps seen on the imaging. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least One Complete Polyp Regression During 6 Months Assessed by ICGA | Baseline through end of study (6 months) | Indocyanine green angiography (ICGA) assessments were performed using the Heidelberg Retinal Angiography 2 (HRA2) machine to measure the Total Lesion Area and the degree of polyp regression. Complete regression was defined as no polyps seen on the imaging. |
| Mean Change From Baseline in Central Retinal Thickness Measured by Optic Coherence Tomography (OCT) | Baseline and Month 6 | High resolution 6 meridian scans were performed to measure central retinal thickness. |
| Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) of the Study Eye at Month 6 | Baseline and Month 6 | 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. |
Countries
Hong Kong, Singapore, South Korea, Taiwan, Thailand
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Verteporfin and Ranibizumab Patients received one treatment at baseline with verteporfin photodynamic therapy (PDT) in the study eye and thereafter based on re-treatment criteria at intervals of at least 90 days. Within 1-24 hours, patients also received Ranibizumab intravitreal injection on Day 1 and at Month 1 and 2 and thereafter according to the re-treatment criteria at intervals of at least 30 days through Day 150. From month 3 onward, re-treatments were determined based on study-specific re-treatment criteria that included evaluation of polyp progression on indocyanine green angiography (ICGA), and assessment of fluorescein angiograms and visual acuity. | 19 |
| Verteporfin Monotherapy Patients received one treatment at baseline with verteporfin photodynamic therapy in the study eye and thereafter based on re-treatment criteria at intervals of at least 90 days. Within 1-24 hours, patients also received Ranibizumab placebo (sham intravitreal injection) on Day 1 and at Month 1 and 2 and thereafter according to the re-treatment criteria at intervals of at least 30 days through Day 150. From month 3 onward, re-treatments were determined based on study-specific re-treatment criteria that included evaluation of polyp progression on indocyanine green angiography (ICGA), and assessment of fluorescein angiograms and visual acuity. | 21 |
| Ranibizumab Monotherapy Patients received one treatment at baseline with verteporfin placebo (with sham photodynamic therapy) in the study eye and thereafter based on re-treatment criteria at intervals of at least 90 days. Within 1-24 hours, patients also received Ranibizumab intravitreal injection on Day 1 and at Month 1 and 2 and thereafter according to the re-treatment criteria at intervals of at least 30 days through Day 150. From month 3 onward, re-treatments were determined based on study-specific re-treatment criteria that included evaluation of polyp progression on indocyanine green angiography (ICGA), and assessment of fluorescein angiograms and visual acuity. | 21 |
| Total | 61 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Verteporfin Monotherapy | Verteporfin and Ranibizumab | Ranibizumab Monotherapy | Total |
|---|---|---|---|---|
| Age Continuous | 62.2 years STANDARD_DEVIATION 9.77 | 63.8 years STANDARD_DEVIATION 8.3 | 69.3 years STANDARD_DEVIATION 8.27 | 65.1 years STANDARD_DEVIATION 9.21 |
| Sex: Female, Male Female | 6 Participants | 8 Participants | 6 Participants | 20 Participants |
| Sex: Female, Male Male | 15 Participants | 11 Participants | 15 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 19 | 9 / 21 | 4 / 21 |
| serious Total, serious adverse events | 1 / 19 | 1 / 21 | 2 / 21 |
Outcome results
Primary
Number of Participants With Complete Regression (CR) of Polyps Measured by Indocyanine Green Angiography (ICGA)
Indocyanine green angiography (ICGA) assessments were performed using the Heidelberg Retinal Angiography 2 (HRA2) machine to measure the Total Lesion Area and the degree of polyp regression. Complete regression was defined as no polyps seen on the imaging.
Time frame: Month 6
Population: Full Analysis Set (FAS) included all patients randomized that received at least 1 application of study drug and had at least 1 post-baseline assessment of ICGA. Last Observation Carried Forward (LOCF) was utilized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Verteporfin and Ranibizumab | Number of Participants With Complete Regression (CR) of Polyps Measured by Indocyanine Green Angiography (ICGA) | 14 Participants |
| Verteporfin Monotherapy | Number of Participants With Complete Regression (CR) of Polyps Measured by Indocyanine Green Angiography (ICGA) | 15 Participants |
| Ranibizumab Monotherapy | Number of Participants With Complete Regression (CR) of Polyps Measured by Indocyanine Green Angiography (ICGA) | 6 Participants |
Secondary
Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) of the Study Eye at Month 6
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 6
Population: Full Analysis Set (FAS) included all patients randomized that received at least 1 application of study drug and had at least 1 post-baseline assessment of ICGA. LOCF was utilized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Verteporfin and Ranibizumab | Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) of the Study Eye at Month 6 | Baseline | 59.8 Letters | Standard Deviation 16.21 |
| Verteporfin and Ranibizumab | Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) of the Study Eye at Month 6 | Change from Baseline at Month 6 | 10.9 Letters | Standard Deviation 10.92 |
| Verteporfin Monotherapy | Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) of the Study Eye at Month 6 | Baseline | 57.2 Letters | Standard Deviation 12.76 |
| Verteporfin Monotherapy | Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) of the Study Eye at Month 6 | Change from Baseline at Month 6 | 7.5 Letters | Standard Deviation 10.65 |
| Ranibizumab Monotherapy | Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) of the Study Eye at Month 6 | Baseline | 49.0 Letters | Standard Deviation 18.05 |
| Ranibizumab Monotherapy | Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) of the Study Eye at Month 6 | Change from Baseline at Month 6 | 9.2 Letters | Standard Deviation 12.39 |
Secondary
Mean Change From Baseline in Central Retinal Thickness Measured by Optic Coherence Tomography (OCT)
High resolution 6 meridian scans were performed to measure central retinal thickness.
Time frame: Baseline and Month 6
Population: Full Analysis Set (FAS) included all patients randomized that received at least 1 application of study drug and had at least 1 post-baseline assessment of ICGA. LOCF was utilized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Verteporfin and Ranibizumab | Mean Change From Baseline in Central Retinal Thickness Measured by Optic Coherence Tomography (OCT) | Baseline | 324.1 micrometers | Standard Deviation 112.72 |
| Verteporfin and Ranibizumab | Mean Change From Baseline in Central Retinal Thickness Measured by Optic Coherence Tomography (OCT) | Change from Baseline at month 6 | -145.6 micrometers | Standard Deviation 118.97 |
| Verteporfin Monotherapy | Mean Change From Baseline in Central Retinal Thickness Measured by Optic Coherence Tomography (OCT) | Change from Baseline at month 6 | -98.1 micrometers | Standard Deviation 104.33 |
| Verteporfin Monotherapy | Mean Change From Baseline in Central Retinal Thickness Measured by Optic Coherence Tomography (OCT) | Baseline | 285.3 micrometers | Standard Deviation 105.64 |
| Ranibizumab Monotherapy | Mean Change From Baseline in Central Retinal Thickness Measured by Optic Coherence Tomography (OCT) | Change from Baseline at month 6 | -65.7 micrometers | Standard Deviation 114.32 |
| Ranibizumab Monotherapy | Mean Change From Baseline in Central Retinal Thickness Measured by Optic Coherence Tomography (OCT) | Baseline | 268.5 micrometers | Standard Deviation 97.84 |
Secondary
Number of Participants With at Least One Complete Polyp Regression During 6 Months Assessed by ICGA
Indocyanine green angiography (ICGA) assessments were performed using the Heidelberg Retinal Angiography 2 (HRA2) machine to measure the Total Lesion Area and the degree of polyp regression. Complete regression was defined as no polyps seen on the imaging.
Time frame: Baseline through end of study (6 months)
Population: Full Analysis Set (FAS) included all patients randomized that received at least 1 application of study drug and had at least 1 post-baseline assessment of ICGA. Last Observation Carried Forward (LOCF) was utilized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Verteporfin and Ranibizumab | Number of Participants With at Least One Complete Polyp Regression During 6 Months Assessed by ICGA | 15 Participants |
| Verteporfin Monotherapy | Number of Participants With at Least One Complete Polyp Regression During 6 Months Assessed by ICGA | 18 Participants |
| Ranibizumab Monotherapy | Number of Participants With at Least One Complete Polyp Regression During 6 Months Assessed by ICGA | 9 Participants |