Age-Related Maculopathy, Choroidal Neovascularization
Conditions
Keywords
Ranibizumab, Lucentis, Verteporfin, Visudyne, Photodynamic therapy
Brief summary
In this pilot study the researchers will evaluate the safety and efficacy of 50% reduced fluence PDT combination therapy with ranibizumab. The researchers hope to gain information regarding the use of reduced fluence PDT combination therapy. The information gained from this pilot study may prompt further definitive studies comparing the safety and efficacy of both standard fluence PDT combination therapy, reduced fluence PDT combination therapy, and ranibizumab monotherapy. The study will compare the use of combination therapy with ranibizumab and verteporfin PDT to ranibizumab alone in patients with exudative age-related macular degeneration (AMD). All patients will receive three consecutive monthly treatments with ranibizumab. Patients will be randomized 1:1:1 to 3 groups. Patients randomized to group 1 will receive only ranibizumab. Patients randomized to group 2 will also receive one treatment with reduced fluence (50% fluence) verteporfin PDT at day 0. Patients randomized to group 3 will also receive one treatment with standard fluence verteporfin PDT. All patients will also be evaluated for possible retreatment with ranibizumab and verteporfin PDT according to established criteria. Thirty patients will be recruited from one U.S. sites. Randomization will occur at the time of entry into the study. Follow-up will continue until month 12 (from day 0) in all subjects.
Interventions
DRUGRanibizumab
intravitreal administered ranibizumab 0.5 mg in 0.05 mL
DRUGVerteporfin
Verteporfin with 50% fluence photodynamic therapy (25 J/cm2)
Sponsors
Novartis
Oklahoma State University Center for Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or Female Patients \> 50 years of age. 2. Patients with primary subfoveal CNV secondary to AMD documented on IVFA and/or OCT. 3. Patient with BCVA of 20/40 to 20/320 in the study eye using Early Treatment Diabetic Retinopathy Study (ETDRS) charts. See definition of ETDRS charts. 4. If both eyes are eligible, only one eye will be evaluated in the study. The eye with lesser visual acuity will be selected as the study eye. 5. Patients must be able and willing to provide written informed consent.
Exclusion criteria
1. Patients receiving prior treatment in the study eye with verteporfin, any focal laser photocoagulation, vitrectomy, or intravitreous injection of antiangiogenic medications, including triamcinolone, pegaptanib, bevacizumab, or ranibizumab. 2. Neovascular membrane from any other retinal disease such as myopic degeneration, histoplasmosis, retinal angiomatous proliferation, or other ocular inflammatory disease. 3. Choroidal neovascular membrane greater than 9 disc diameters in size. 4. Previous posterior vitrectomy in the study eye. 5. Concurrent disease in the study eye that could compromise visual acuity or require medical or surgical intervention during the study period. 6. Pregnant women or premenopausal women not using adequate contraception. 7. History of allergy to fluorescein, Visudyne, Lucentis. 8. Inability to comply with study or follow up procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in BCVA of ETDRS Letters From Baseline at 12 Months | 12 months | Visual acuity is often measured using a chart called the ETDRS chart (Early Treatment Diabetic Retinopathy Study). A letter score is calculated based on the number of letters that can be correctly identified from specified distances. Higher letter scores correspond to better visual acuity. Lower letter scores mean poorer visual acuity. In this study the baseline visual acuity in letters is subtracted from the visual acuity in letters measured at the 12 month visit providing a letter score of vision gain or vision loss. |
| Mean Letters Gained of Best Corrected Visual Acuity Using ETDRS Protocol | 12 months | Visual acuity is often measured using a chart called the ETDRS chart (Early Treatment Diabetic Retinopathy Study). A letter score is calculated based on the number of letters that can be correctly identified from specified distances. Higher letter scores correspond to better visual acuity. Lower letter scores mean poorer visual acuity. In this study the baseline visual acuity in letters is subtracted from the visual acuity in letters measured at the 12 month visit providing a letter score of vision gain or vision loss. |
Secondary
| Measure | Time frame |
|---|---|
| Average Number of PDT Retreatments Over 12 Months | 12 months |
| Central Macular Thickness Reduction on OCT | 12 months |
| Average Number of Ranibizumab Retreatments Over 12 Months | 12 months |
| Time to First Retreatment After Loading Doses | 12 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard Fluence PDT Standard Fluence Photodynamic Therapy combined with ranibizumab | 10 |
| 50% Fluence PDT Verteporfin at 50% fluence photodynamic therapy combined with ranibizumab | 11 |
| Ranibizumab Ranibizumab monotherapy | 10 |
| Total | 31 |
Baseline characteristics
| Characteristic | 50% Fluence PDT | Ranibizumab | Standard Fluence PDT | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 9 Participants | 9 Participants | 27 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 1 Participants | 1 Participants | 4 Participants |
| Age, Continuous | 73.4 years STANDARD_DEVIATION 2.1 | 76.3 years STANDARD_DEVIATION 2.8 | 76.9 years STANDARD_DEVIATION 3.1 | 74 years STANDARD_DEVIATION 2.7 |
| Region of Enrollment United States | 11 participants | 10 participants | 10 participants | 31 participants |
| Sex: Female, Male Female | 7 Participants | 8 Participants | 8 Participants | 23 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 2 Participants | 8 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 | 0 / 10 | 0 / 11 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 11 | 2 / 10 |
Outcome results
Primary
Mean Change in BCVA of ETDRS Letters From Baseline at 12 Months
Visual acuity is often measured using a chart called the ETDRS chart (Early Treatment Diabetic Retinopathy Study). A letter score is calculated based on the number of letters that can be correctly identified from specified distances. Higher letter scores correspond to better visual acuity. Lower letter scores mean poorer visual acuity. In this study the baseline visual acuity in letters is subtracted from the visual acuity in letters measured at the 12 month visit providing a letter score of vision gain or vision loss.
Time frame: 12 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Standard Fluence PDT | Mean Change in BCVA of ETDRS Letters From Baseline at 12 Months | 5.9 Letters |
| Reduced Fluence PDT | Mean Change in BCVA of ETDRS Letters From Baseline at 12 Months | 7.6 Letters |
| Ranibizumab Monotherapy | Mean Change in BCVA of ETDRS Letters From Baseline at 12 Months | 16.4 Letters |
Primary
Mean Letters Gained of Best Corrected Visual Acuity Using ETDRS Protocol
Visual acuity is often measured using a chart called the ETDRS chart (Early Treatment Diabetic Retinopathy Study). A letter score is calculated based on the number of letters that can be correctly identified from specified distances. Higher letter scores correspond to better visual acuity. Lower letter scores mean poorer visual acuity. In this study the baseline visual acuity in letters is subtracted from the visual acuity in letters measured at the 12 month visit providing a letter score of vision gain or vision loss.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Fluence PDT | Mean Letters Gained of Best Corrected Visual Acuity Using ETDRS Protocol | 5.9 letters | Standard Deviation 6.3 |
| Reduced Fluence PDT | Mean Letters Gained of Best Corrected Visual Acuity Using ETDRS Protocol | 7.6 letters | Standard Deviation 4 |
| Ranibizumab Monotherapy | Mean Letters Gained of Best Corrected Visual Acuity Using ETDRS Protocol | 16.4 letters | Standard Deviation 4 |
Secondary
Average Number of PDT Retreatments Over 12 Months
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Fluence PDT | Average Number of PDT Retreatments Over 12 Months | 0.67 Number of Treatments | Standard Deviation 0.24 |
| Reduced Fluence PDT | Average Number of PDT Retreatments Over 12 Months | 0.55 Number of Treatments | Standard Deviation 0.22 |
Secondary
Average Number of Ranibizumab Retreatments Over 12 Months
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Fluence PDT | Average Number of Ranibizumab Retreatments Over 12 Months | 2.67 Number of Treatments | Standard Deviation 0.53 |
| Reduced Fluence PDT | Average Number of Ranibizumab Retreatments Over 12 Months | 2.91 Number of Treatments | Standard Deviation 0.62 |
| Ranibizumab Monotherapy | Average Number of Ranibizumab Retreatments Over 12 Months | 4.14 Number of Treatments | Standard Deviation 0.72 |
Secondary
Central Macular Thickness Reduction on OCT
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Fluence PDT | Central Macular Thickness Reduction on OCT | 42.9 micron (um) | Standard Deviation 20.1 |
| Reduced Fluence PDT | Central Macular Thickness Reduction on OCT | 76.1 micron (um) | Standard Deviation 37.8 |
| Ranibizumab Monotherapy | Central Macular Thickness Reduction on OCT | 34.9 micron (um) | Standard Deviation 10.9 |
Secondary
Time to First Retreatment After Loading Doses
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Fluence PDT | Time to First Retreatment After Loading Doses | 2.86 Month | Standard Deviation 0.38 |
| Reduced Fluence PDT | Time to First Retreatment After Loading Doses | 2.90 Month | Standard Deviation 0.71 |
| Ranibizumab Monotherapy | Time to First Retreatment After Loading Doses | 2.86 Month | Standard Deviation 0.63 |