Choroidal Neovascularization, Macular Degeneration
Conditions
Keywords
Macular Degeneration, AMD, CNV, Choroidal neovascularization, Photodynamic therapy, CNV Secondary to Age Related Macular Degeneration
Brief summary
The objective of this study is to determine if combination therapy (reduced-fluence Visudyne followed by Lucentis \[within 2 hours\] or either of two regimens of reduced-fluence Visudyne followed by Lucentis-Dexamethasone triple therapy \[within 2 hours\]) reduces retreatment rates compared with Lucentis monotherapy while maintaining similar vision outcomes and an acceptable safety profile.
Interventions
DRUGverteporfin
Reduced-fluence Visudyne (25 J/cm2, 300 mW/cm2, 83 seconds)
DRUGranibizumab
0.5 mg intravitreal injection
DRUGdexamethasone
0.5 mg intravitreal injection
Sponsors
QLT Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Treatment naive for choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) in the study eye except for laser treatment outside the subfoveal area * Subfoveal CNV due to AMD * CNV must be = or \>50 % of the entire lesion * All lesion composition types with a lesion greatest linear dimension (GLD) \< 5400 microns (approximately = or \<9 disc areas \[DA\]) * Best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA score) of 25 - 73 letters (approximate Snellen equivalent of 20/40 - 20/320), inclusive
Exclusion criteria
* Subfoveal geographic atrophy or subfoveal fibrosis of the study eye * Intraocular surgery within 3 months of enrollment * Inability to attend the protocol-required visits * Known allergies or hypersensitivity to any of the study treatments. * Other systemic diseases or active uncontrolled infections that would make subject a poor medical risk * Uncontrolled glaucoma, defined as (1)subject is on \>1 glaucoma medication (includes combination treatments) or (2)subject has glaucoma that could lead to progressive visual field deterioration * If subject has had a stroke within the last year
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Number of Retreatments (Day 0 Excluded) | Month 1 to Month 12 | Retreatment was defined in the protocol as study treatment administered after Day 0. For the analyses of retreatment, any study treatment that was administered was considered to be a retreatment, and combination therapy was considered to be one retreatment, even though two or three treatment procedures were done. In the combination therapy groups, if a ranibizumab injection was given because retreatment was indicated and the previous combination treatment was less than 2 months before, the ranibizumab injection was counted as a retreatment. |
| Mean Change From Baseline in Study Eye Best-corrected VA Score (ETDRS Chart) | Baseline to Month 12 | Early Treatment Diabetic Retinopathy Study (ETDRS) method at 4 meters. Worst = 0; best = 100 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With >=15 Letters of Visual Acuity Gained From Baseline | Baseline to Month 12, Baseline to Month 24 | — |
| Percentage of Subjects With >=0 Letter Gain of Visual Acuity From Baseline | Baseline to Month 12, Baseline to Month 24 | — |
| Mean Number of Retreatments (Day 0 Excluded) | Month 1 to Month 24 | Retreatment was defined in the protocol as study treatment administered after Day 0. For the analyses of retreatment, any study treatment that was administered was considered to be a retreatment, and combination therapy was considered to be one retreatment, even though two or three treatment procedures were done. In the combination therapy groups, if a ranibizumab injection was given because retreatment was indicated and the previous combination treatment was less than 2 months before, the ranibizumab injection was counted as a retreatment. |
| Mean Change From Baseline in Central Retinal Thickness | Baseline to Month 12, Baseline to Month 24 | — |
| Mean Change From Baseline in Lesion Size | Baseline to Month 12, Baseline to Month 24 | Mean change from baseline in lesion size measured as greatest linear dimension (GLD) of the lesion |
| Percentage of Subjects With >=15 Letters of Visual Acuity Lost From Baseline | Baseline to Month 12, Baseline to Month 24 | — |
| Mean Change From Baseline in Study Eye Best-Corrected VA Score | Baseline to Month 24 | Early Treatment Diabetic Retinopathy Study (ETDRS) method at 4 meters. Worst = 0; best = 100 |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 1/4 Fluence Triple Therapy Very low fluence Visudyne (15 J/cm2: 180 mW/cm2 for 83 seconds) followed by intravitreal Lucentis (0.5 mg)-Dexamethasone (0.5 mg) triple therapy \[within 2 hours\] on Day 0 and then as required every 2 months thereafter | 39 |
| 1/2 Fluence Triple Therapy Reduced-fluence Visudyne (25 J/cm2: 300 mW/cm2 for 83 seconds) followed by intravitreal Lucentis (0.5 mg)-Dexamethasone (0.5 mg) triple therapy \[within 2 hours\] on Day 0 and then as required every 2 months thereafter | 39 |
| 1/2 Fluence Double Therapy Reduced-fluence Visudyne (25 J/cm2: 300 mW/cm2 for 83 seconds) followed by intravitreal Lucentis (0.5 mg) double therapy \[within 2 hours\] | 43 |
| Ranibizumab Lucentis monotherapy (0.5 mg)on Day 0, Month 1, and Month 2, and then as required monthly thereafter | 41 |
| Total | 162 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 1 | 2 |
| Overall Study | Death | 0 | 3 | 2 | 5 |
| Overall Study | Lost to Follow-up | 0 | 0 | 3 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | 1/4 Fluence Triple Therapy | Total | Ranibizumab | 1/2 Fluence Double Therapy | 1/2 Fluence Triple Therapy |
|---|---|---|---|---|---|
| Age Continuous | 78 years STANDARD_DEVIATION 8 | 79 years STANDARD_DEVIATION 7 | 79 years STANDARD_DEVIATION 5 | 79 years STANDARD_DEVIATION 6 | 78 years STANDARD_DEVIATION 8 |
| Central retinal thickness | 318.3 micron STANDARD_DEVIATION 95.9 | 326.3 micron STANDARD_DEVIATION 105.4 | 311.9 micron STANDARD_DEVIATION 95.5 | 337.3 micron STANDARD_DEVIATION 121.4 | 337.3 micron STANDARD_DEVIATION 106.8 |
| Lesion composition Minimally classic | 6 participants | 27 participants | 8 participants | 9 participants | 4 participants |
| Lesion composition Occult no classic | 10 participants | 64 participants | 18 participants | 20 participants | 16 participants |
| Lesion composition Predominantly classic | 23 participants | 71 participants | 15 participants | 14 participants | 19 participants |
| Lesion size (greatest linear dimension) | 2778.8 micron STANDARD_DEVIATION 1025.6 | 2860.1 micron STANDARD_DEVIATION 1049.4 | 3118.4 micron STANDARD_DEVIATION 1155.7 | 2796.1 micron STANDARD_DEVIATION 1122.8 | 2740.1 micron STANDARD_DEVIATION 846.1 |
| Sex: Female, Male Female | 20 Participants | 95 Participants | 28 Participants | 23 Participants | 24 Participants |
| Sex: Female, Male Male | 19 Participants | 67 Participants | 13 Participants | 20 Participants | 15 Participants |
| Study Eye Best-corrected Visual Acuity Score (ETDRS chart) | 58.1 Letters read on ETDRS chart STANDARD_DEVIATION 11.8 | 55.7 Letters read on ETDRS chart STANDARD_DEVIATION 12 | 56.0 Letters read on ETDRS chart STANDARD_DEVIATION 13.1 | 53.3 Letters read on ETDRS chart STANDARD_DEVIATION 11.9 | 55.6 Letters read on ETDRS chart STANDARD_DEVIATION 11.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 36 / 39 | 36 / 39 | 36 / 43 | 37 / 41 |
| serious Total, serious adverse events | 10 / 39 | 13 / 39 | 15 / 43 | 19 / 41 |
Outcome results
Primary
Mean Change From Baseline in Study Eye Best-corrected VA Score (ETDRS Chart)
Early Treatment Diabetic Retinopathy Study (ETDRS) method at 4 meters. Worst = 0; best = 100
Time frame: Baseline to Month 12
Population: Intent-to-treat and last observation carried forward
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1/4 Fluence Triple Therapy | Mean Change From Baseline in Study Eye Best-corrected VA Score (ETDRS Chart) | 3.6 Letters read on ETDRS chart | 95% Confidence Interval 13.8 |
| 1/2 Fluence Triple Therapy | Mean Change From Baseline in Study Eye Best-corrected VA Score (ETDRS Chart) | 6.8 Letters read on ETDRS chart | 95% Confidence Interval 13.4 |
| 1/2 Fluence Double Therapy | Mean Change From Baseline in Study Eye Best-corrected VA Score (ETDRS Chart) | 5.0 Letters read on ETDRS chart | 95% Confidence Interval 14.2 |
| Ranibizumab | Mean Change From Baseline in Study Eye Best-corrected VA Score (ETDRS Chart) | 6.5 Letters read on ETDRS chart | 95% Confidence Interval 15.5 |
Primary
Mean Number of Retreatments (Day 0 Excluded)
Retreatment was defined in the protocol as study treatment administered after Day 0. For the analyses of retreatment, any study treatment that was administered was considered to be a retreatment, and combination therapy was considered to be one retreatment, even though two or three treatment procedures were done. In the combination therapy groups, if a ranibizumab injection was given because retreatment was indicated and the previous combination treatment was less than 2 months before, the ranibizumab injection was counted as a retreatment.
Time frame: Month 1 to Month 12
Population: Intent-to-treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1/4 Fluence Triple Therapy | Mean Number of Retreatments (Day 0 Excluded) | 3.97 number of retreatments | 95% Confidence Interval 3.12 |
| 1/2 Fluence Triple Therapy | Mean Number of Retreatments (Day 0 Excluded) | 3.00 number of retreatments | 95% Confidence Interval 2.55 |
| 1/2 Fluence Double Therapy | Mean Number of Retreatments (Day 0 Excluded) | 4.05 number of retreatments | 95% Confidence Interval 2.93 |
| Ranibizumab | Mean Number of Retreatments (Day 0 Excluded) | 5.39 number of retreatments | 95% Confidence Interval 2.97 |
Secondary
Mean Change From Baseline in Central Retinal Thickness
Time frame: Baseline to Month 12, Baseline to Month 24
Population: Intent-to-treat and last observation carried forward
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1/4 Fluence Triple Therapy | Mean Change From Baseline in Central Retinal Thickness | Baseline to Month 12 | -115.9 micron | Standard Deviation 97.4 |
| 1/4 Fluence Triple Therapy | Mean Change From Baseline in Central Retinal Thickness | Baseline to Month 24 | -110.2 micron | Standard Deviation 93.6 |
| 1/2 Fluence Triple Therapy | Mean Change From Baseline in Central Retinal Thickness | Baseline to Month 24 | -123.9 micron | Standard Deviation 97.1 |
| 1/2 Fluence Triple Therapy | Mean Change From Baseline in Central Retinal Thickness | Baseline to Month 12 | -122.2 micron | Standard Deviation 104.8 |
| 1/2 Fluence Double Therapy | Mean Change From Baseline in Central Retinal Thickness | Baseline to Month 12 | -137.8 micron | Standard Deviation 122.3 |
| 1/2 Fluence Double Therapy | Mean Change From Baseline in Central Retinal Thickness | Baseline to Month 24 | -121.0 micron | Standard Deviation 126.6 |
| Ranibizumab | Mean Change From Baseline in Central Retinal Thickness | Baseline to Month 12 | -100.3 micron | Standard Deviation 90.1 |
| Ranibizumab | Mean Change From Baseline in Central Retinal Thickness | Baseline to Month 24 | -103.1 micron | Standard Deviation 99.1 |
Secondary
Mean Change From Baseline in Lesion Size
Mean change from baseline in lesion size measured as greatest linear dimension (GLD) of the lesion
Time frame: Baseline to Month 12, Baseline to Month 24
Population: Intent-to-treat and last observation carried forward
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1/4 Fluence Triple Therapy | Mean Change From Baseline in Lesion Size | Baseline to Month 12 | 77.2 micron | Standard Deviation 960.3 |
| 1/4 Fluence Triple Therapy | Mean Change From Baseline in Lesion Size | Baseline to Month 24 | 94.8 micron | Standard Deviation 865.1 |
| 1/2 Fluence Triple Therapy | Mean Change From Baseline in Lesion Size | Baseline to Month 24 | -103.3 micron | Standard Deviation 1326.1 |
| 1/2 Fluence Triple Therapy | Mean Change From Baseline in Lesion Size | Baseline to Month 12 | -20.4 micron | Standard Deviation 1550.7 |
| 1/2 Fluence Double Therapy | Mean Change From Baseline in Lesion Size | Baseline to Month 12 | 152.0 micron | Standard Deviation 1415.5 |
| 1/2 Fluence Double Therapy | Mean Change From Baseline in Lesion Size | Baseline to Month 24 | -112.5 micron | Standard Deviation 1209.4 |
| Ranibizumab | Mean Change From Baseline in Lesion Size | Baseline to Month 12 | -192.6 micron | Standard Deviation 672.5 |
| Ranibizumab | Mean Change From Baseline in Lesion Size | Baseline to Month 24 | -205.3 micron | Standard Deviation 653.4 |
Secondary
Mean Change From Baseline in Study Eye Best-Corrected VA Score
Early Treatment Diabetic Retinopathy Study (ETDRS) method at 4 meters. Worst = 0; best = 100
Time frame: Baseline to Month 24
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 1/4 Fluence Triple Therapy | Mean Change From Baseline in Study Eye Best-Corrected VA Score | -0.2 Letters read on ETDRS chart |
| 1/2 Fluence Triple Therapy | Mean Change From Baseline in Study Eye Best-Corrected VA Score | 1.1 Letters read on ETDRS chart |
| 1/2 Fluence Double Therapy | Mean Change From Baseline in Study Eye Best-Corrected VA Score | -0.3 Letters read on ETDRS chart |
| Ranibizumab | Mean Change From Baseline in Study Eye Best-Corrected VA Score | 4.4 Letters read on ETDRS chart |
Secondary
Mean Number of Retreatments (Day 0 Excluded)
Retreatment was defined in the protocol as study treatment administered after Day 0. For the analyses of retreatment, any study treatment that was administered was considered to be a retreatment, and combination therapy was considered to be one retreatment, even though two or three treatment procedures were done. In the combination therapy groups, if a ranibizumab injection was given because retreatment was indicated and the previous combination treatment was less than 2 months before, the ranibizumab injection was counted as a retreatment.
Time frame: Month 1 to Month 24
Population: Intent-to-treat
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 1/4 Fluence Triple Therapy | Mean Number of Retreatments (Day 0 Excluded) | 5.92 number of retreatments |
| 1/2 Fluence Triple Therapy | Mean Number of Retreatments (Day 0 Excluded) | 4.34 number of retreatments |
| 1/2 Fluence Double Therapy | Mean Number of Retreatments (Day 0 Excluded) | 5.92 number of retreatments |
| Ranibizumab | Mean Number of Retreatments (Day 0 Excluded) | 8.68 number of retreatments |
Secondary
Percentage of Subjects With >=0 Letter Gain of Visual Acuity From Baseline
Time frame: Baseline to Month 12, Baseline to Month 24
Population: Intent-to-treat and last observation carried forward
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 1/4 Fluence Triple Therapy | Percentage of Subjects With >=0 Letter Gain of Visual Acuity From Baseline | Baseline to Month 12 | 64.1 Percentage of participants |
| 1/4 Fluence Triple Therapy | Percentage of Subjects With >=0 Letter Gain of Visual Acuity From Baseline | Baseline to Month 24 | 61.5 Percentage of participants |
| 1/2 Fluence Triple Therapy | Percentage of Subjects With >=0 Letter Gain of Visual Acuity From Baseline | Baseline to Month 24 | 66.7 Percentage of participants |
| 1/2 Fluence Triple Therapy | Percentage of Subjects With >=0 Letter Gain of Visual Acuity From Baseline | Baseline to Month 12 | 82.1 Percentage of participants |
| 1/2 Fluence Double Therapy | Percentage of Subjects With >=0 Letter Gain of Visual Acuity From Baseline | Baseline to Month 12 | 69.8 Percentage of participants |
| 1/2 Fluence Double Therapy | Percentage of Subjects With >=0 Letter Gain of Visual Acuity From Baseline | Baseline to Month 24 | 60.5 Percentage of participants |
| Ranibizumab | Percentage of Subjects With >=0 Letter Gain of Visual Acuity From Baseline | Baseline to Month 12 | 70.7 Percentage of participants |
| Ranibizumab | Percentage of Subjects With >=0 Letter Gain of Visual Acuity From Baseline | Baseline to Month 24 | 70.7 Percentage of participants |
Secondary
Percentage of Subjects With >=15 Letters of Visual Acuity Gained From Baseline
Time frame: Baseline to Month 12, Baseline to Month 24
Population: Intent-to-treat and last observation carried forward
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 1/4 Fluence Triple Therapy | Percentage of Subjects With >=15 Letters of Visual Acuity Gained From Baseline | Baseline to Month 12 | 25.6 Percentage of participants |
| 1/4 Fluence Triple Therapy | Percentage of Subjects With >=15 Letters of Visual Acuity Gained From Baseline | Baseline to Month 24 | 20.5 Percentage of participants |
| 1/2 Fluence Triple Therapy | Percentage of Subjects With >=15 Letters of Visual Acuity Gained From Baseline | Baseline to Month 24 | 15.4 Percentage of participants |
| 1/2 Fluence Triple Therapy | Percentage of Subjects With >=15 Letters of Visual Acuity Gained From Baseline | Baseline to Month 12 | 30.8 Percentage of participants |
| 1/2 Fluence Double Therapy | Percentage of Subjects With >=15 Letters of Visual Acuity Gained From Baseline | Baseline to Month 12 | 25.6 Percentage of participants |
| 1/2 Fluence Double Therapy | Percentage of Subjects With >=15 Letters of Visual Acuity Gained From Baseline | Baseline to Month 24 | 16.3 Percentage of participants |
| Ranibizumab | Percentage of Subjects With >=15 Letters of Visual Acuity Gained From Baseline | Baseline to Month 12 | 24.4 Percentage of participants |
| Ranibizumab | Percentage of Subjects With >=15 Letters of Visual Acuity Gained From Baseline | Baseline to Month 24 | 26.8 Percentage of participants |
Secondary
Percentage of Subjects With >=15 Letters of Visual Acuity Lost From Baseline
Time frame: Baseline to Month 12, Baseline to Month 24
Population: Intent-to-treat and last observation carried forward
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 1/4 Fluence Triple Therapy | Percentage of Subjects With >=15 Letters of Visual Acuity Lost From Baseline | Baseline to Month 12 | 12.8 Percentage of participants |
| 1/4 Fluence Triple Therapy | Percentage of Subjects With >=15 Letters of Visual Acuity Lost From Baseline | Baseline to Month 24 | 20.5 Percentage of participants |
| 1/2 Fluence Triple Therapy | Percentage of Subjects With >=15 Letters of Visual Acuity Lost From Baseline | Baseline to Month 24 | 15.4 Percentage of participants |
| 1/2 Fluence Triple Therapy | Percentage of Subjects With >=15 Letters of Visual Acuity Lost From Baseline | Baseline to Month 12 | 7.7 Percentage of participants |
| 1/2 Fluence Double Therapy | Percentage of Subjects With >=15 Letters of Visual Acuity Lost From Baseline | Baseline to Month 12 | 11.6 Percentage of participants |
| 1/2 Fluence Double Therapy | Percentage of Subjects With >=15 Letters of Visual Acuity Lost From Baseline | Baseline to Month 24 | 20.9 Percentage of participants |
| Ranibizumab | Percentage of Subjects With >=15 Letters of Visual Acuity Lost From Baseline | Baseline to Month 12 | 7.3 Percentage of participants |
| Ranibizumab | Percentage of Subjects With >=15 Letters of Visual Acuity Lost From Baseline | Baseline to Month 24 | 14.6 Percentage of participants |