Visual Impairment Due to Choroidal Neovascularization (CNV) Secondary to Pathologic Myopia (PM)
Conditions
Keywords
vision loss,PM,CNV,ranibizumab,verteporfinPDT,Brilliance
Brief summary
This study was designed to evaluate the efficacy and safety of two different dosing regimens of 0.5 mg ranibizumab given as intravitreal injection in comparison to verteporfin PDT in patients with visual impairment due to choroidal neovascularization secondary to pathologic myopia (PM)
Detailed description
This was a phase III, multi-center, randomized, double-masked, active-controlled study comparing 0.5 mg ranibizumab vs. vPDT therapy. The study included 15 scheduled visits over 12 months, and there were to be two additional visits (2a, 3a) for subset of patients in whom PK analysis were performed. There were 3 periods in this study: Screening period-from Day -14 to Baseline; Treatment period-from Baseline to Month 11; Follow-up period-from Month 11 to Month 12 Patients entered the 11 months Treatment period at Visit 2 (Day 1) if eligibility criteria were met and were randomized in three treatment groups Group I ranibizumab 0.5 mg driven by VA stability criteria or Group II ranibizumab 0.5 mg driven by disease activity criteria or Group III vPDT (randomization ratio of 2:2:1) and received first treatment of either a ranibizumab injection and sham vPDT or sham injection and active vPDT and will return to the clinical center within 7 days to undergo safety assessments as well as assessments of the effect of treatment by the evaluating investigator. The following visits were performed at one month intervals starting at Visit 4 and continuing through Visit 14. At all monthly visits (at/from Month 2 for group I, at/from Month 1 for group II and at/from Month 3 for group III) the decision for treatment were made by the evaluating investigator based on the VA stability criteria and on the disease activity criteria. At Month 3 (visit 6) and at all following monthly visits for all three groups one of the three options can recommended by evaluating investigator: a) ranibizumab 0.5 mg, b) ranibizumab 0.5 mg + vPDT; c) vPDT. The treating investigator were then perform treatment based on randomization and masking requirements. At each monthly visit, patients had a safety evaluation by the evaluating investigator prior to study treatment, consisting of visual acuity measurements, ophthalmic examinations and evaluation of adverse events and vital signs. Routine hematology, chemistry, and urinalysis profiles were obtained at Visit 6, 9 and 12 (Month 3, 6 and 9). At Month 12 several procedures and assessments were performed which are required at study completion visit.
Interventions
0.5 mg ranibizumab (intravitreal injections)
0.5 mg ranibizumab (intravitreal injections)
DRUGVerteporfin PDT
Verteporfin for intravenous injection delivered by intravenous infusion followed by the light application
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Visual impairment due to CNV secondary to PM. * Best corrected visual acuity in the study eye \> 24 and \< 78 ETDRS letters. * High myopia (\> -6D), * anterio-posterior elongation \> 26 mm; posterior changes compatible with the pathologic myopia. * Either CNV locations in the study eye: subfoveal, juxtafoveal, extrafoveal.
Exclusion criteria
* Some preexisting eye disorders or systemic diseases;-Blood pressure \> 150/90 mmHg * Prior focal/grid laser to the macular area -History of treatment with any anti-VEGF or verteporfin PDT in the study eye * Intravitreal treatment with corticosteroids or intraocular surgery within last 3 months in the study eye
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline BCVA to the Average Level of BCVA Over All Monthly Assessments From Month 1 to Month 3 | From Baseline to Month 3 | Best corrected visual acuity (BCVA) was tested using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) charts testing protocol. VA measurements were taken in a sitting position at an initial test distance of 4 meters using ETDRS charts. The overall BCVA score was calculated using the BCVA worksheet, which was kept in the source data and the score was recorded in the eCRF. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Average Change in BCVA Score From Baseline to Month 1 Through Month 12 | From Baseline to Month 12 | Best corrected visual acuity (BCVA) was tested using the ETDRS VA testing protocol. VA measurements were taken in a sitting position at an initial test distance of 4 meters using ETDRS charts. The overall BCVA score was calculated using the BCVA worksheet, which was kept in the source data and the score was recorded in the eCRF. Between treatment comparison of 0.5 mg ranibizumab intravitreal injections driven by disease activity re-treatment criteria (Group II) versus 0.5 mg ranibizumab intravitreal injections driven by visual acuity stability criteria (Group I) based on the average BCVA change from Baseline to Month 1 through Month 12 |
| Mean Change From Baseline in Visual Acuity Over Time | Change from baseline at months 3, 6, and 12 | Best corrected visual acuity (BCVA) was tested using the ETDRS VA testing protocol. VA measurements were taken in a sitting position at an initial test distance of 4 meters using ETDRS charts. The overall BCVA score was calculated using the BCVA worksheet, which was kept in the source data and the score was recorded in the eCRF. |
| Categorized BCVA Changes at Months 3, 6 and 12 Compared With Baseline for the Study Eye | From Baseline to Month 12 | ETDRS VA testing protocol. VA measurements were taken in a sitting position at an initial test distance of 4 meters using ETDRS charts. The overall BCVA score was calculated using the BCVA worksheet, which was kept in the source data and the score was recorded in the eCRF. |
| Change From Baseline BCVA to the Average Level of BCVA Over All Monthly Assessments From Month 1 to Month 6 | From Baseline to Month 6 | Best corrected visual acuity (BCVA) was tested using the early treatment diabetic retinopathy study (ETDRS) VA testing protocol. VA measurements were taken in a sitting position at an initial test distance of 4 meters using ETDRS charts. The overall BCVA score was calculated using the BCVA worksheet, which was kept in the source data and the score was recorded in the eCRF. Between treatment comparison of 0.5 mg ranibizumab intravitreal injections driven by disease activity re-treatment criteria (Group II) versus 0.5 mg ranibizumab intravitreal injections driven by visual acuity stability criteria (Group I) based on the average BCVA change from Baseline to Month 1 through Month 6. |
| Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12 | From Baseline until Month 12 | CNV leakage is assessed via fluorescein angiography (center involvement) category: definite, questionable, absent, can't grade, and missing. |
| NEI-VFQ-25 - Change From Baseline to Month 3, 6 and 12 | Change from baseline at month 3, 6 and 12 | The VFQ-25 consists of 25 vision related questions across 11 vision related subscales, including general vision, ocular pain, near activities, distance activities, social function, mental health, role difficulties, dependency, driving, color vision and peripheral vision, and a general health rating. Items are converted to a 0-100 scale on each subscale and for the composite score where higher scores represents better functioning. |
| Number of Ranibizumab Injections Received in the Study Eye for the Ranibizumab Groups | From Baseline to Month 12 | To assess treatment pattern with ranibizumab |
| Mean Change From Baseline Over Time in Central Sub-field Thickness (CSFT) | Baseline, Month 3, Month 6, and Month 12 | Central sub-field thickness (CSFT) is a variable assessed via Optical Coherence Tomography (OCT). OCT was performed prior to any study drug administration to assess presence of intra, subretinal fluid, or increase of CSFT. |
Countries
China, Hong Kong, India, Philippines, South Korea, Thailand
Participant flow
Recruitment details
Randomized Set: consisted of all randomized patients. Patients were considered randomized when they had been given a randomization number.
Pre-assignment details
In total, 457 patients were randomized into this study in a ratio of 2:2:1: 182 to Group I, 184 to Group II, and 91 to Group III.
Participants by arm
| Arm | Count |
|---|---|
| Group I 0.5 mg ranibizumab driven by visual acuity stability criteria | 182 |
| Group II 0.5 mg ranibizumab driven by disease activity criteria | 184 |
| Group III verteporfin PDT (driven by disease activity). Patients received vPDT on Day 1. From Month 3, based on disease activity vPDT, Ranibizumab 0.5 mg, or combo of Ranibizumab and vPDT was selected for treatment | 91 |
| Total | 457 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Administrative problems | 0 | 2 | 0 |
| Overall Study | Adverse Event | 1 | 2 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 7 | 3 | 7 |
Baseline characteristics
| Characteristic | Group I | Group II | Group III | Total |
|---|---|---|---|---|
| Age, Continuous | 52.0 Years STANDARD_DEVIATION 12.01 | 51.5 Years STANDARD_DEVIATION 12.13 | 49.1 Years STANDARD_DEVIATION 14.81 | 51.2 Years STANDARD_DEVIATION 12.68 |
| Sex: Female, Male Female | 128 Participants | 116 Participants | 67 Participants | 311 Participants |
| Sex: Female, Male Male | 54 Participants | 68 Participants | 24 Participants | 146 Participants |
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 | 102 / 182 | 116 / 185 | 50 / 75 | 8 / 14 |
| serious Total, serious adverse events | 7 / 182 | 15 / 185 | 8 / 75 | 0 / 14 |
Outcome results
Primary
Change From Baseline BCVA to the Average Level of BCVA Over All Monthly Assessments From Month 1 to Month 3
Best corrected visual acuity (BCVA) was tested using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) charts testing protocol. VA measurements were taken in a sitting position at an initial test distance of 4 meters using ETDRS charts. The overall BCVA score was calculated using the BCVA worksheet, which was kept in the source data and the score was recorded in the eCRF.
Time frame: From Baseline to Month 3
Population: Full Analysis Set (FAS): consisted of all patients to whom study treatment were assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment group they were assigned to at randomization.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I | Change From Baseline BCVA to the Average Level of BCVA Over All Monthly Assessments From Month 1 to Month 3 | Baseline | 53.7 ETDRS letters | Standard Deviation 12.65 |
| Group I | Change From Baseline BCVA to the Average Level of BCVA Over All Monthly Assessments From Month 1 to Month 3 | Average Month 1 to Month 3 | 63.1 ETDRS letters | Standard Deviation 12.8 |
| Group II | Change From Baseline BCVA to the Average Level of BCVA Over All Monthly Assessments From Month 1 to Month 3 | Baseline | 54.2 ETDRS letters | Standard Deviation 13.01 |
| Group II | Change From Baseline BCVA to the Average Level of BCVA Over All Monthly Assessments From Month 1 to Month 3 | Average Month 1 to Month 3 | 63.9 ETDRS letters | Standard Deviation 13.28 |
| Group III | Change From Baseline BCVA to the Average Level of BCVA Over All Monthly Assessments From Month 1 to Month 3 | Baseline | 52.6 ETDRS letters | Standard Deviation 12.29 |
| Group III | Change From Baseline BCVA to the Average Level of BCVA Over All Monthly Assessments From Month 1 to Month 3 | Average Month 1 to Month 3 | 57.1 ETDRS letters | Standard Deviation 13.21 |
Comparison: 2 one-sided hypotheses were tested under the Type I error rate of 0.025, using the Hochberg procedure: H01: μRanibizumab-I - μvPDT ≤ 0 vs. HA1: μRanibizumab-I - μvPDT \> 0 and H02: μRanibizumab-II - μvPDT ≤ 0 vs. HA2: μRanibizumab-II - μvPDT \> 0, where μRanibizumab-I, μRanibizumab-II and μvPDT were the means of the primary efficacy variable for ranibizumab treatment Group I, ranibizumab treatment Group II, and vPDT treatment Group III, respectively.p-value: <0.00195% CI: [3.3, 7.1]Cochran-Mantel-Haenszel
Comparison: The following 2 one-sided hypotheses were tested under the Type I error rate of 0.025, using the Hochberg procedure:~H01: μRanibizumab-I - μvPDT ≤ 0 vs. HA1: μRanibizumab-I - μvPDT \> 0 and H02: μRanibizumab-II - μvPDT ≤ 0 vs. HA2: μRanibizumab-II - μvPDT \> 0, where μRanibizumab-I, μRanibizumab-II and μvPDT were the means of the primary efficacy variable for ranibizumab treatment Group I, ranibizumab treatment Group II, and vPDT treatment Group III, respectively.p-value: <0.00195% CI: [3.5, 7.6]Cochran-Mantel-Haenszel
Secondary
Categorized BCVA Changes at Months 3, 6 and 12 Compared With Baseline for the Study Eye
ETDRS VA testing protocol. VA measurements were taken in a sitting position at an initial test distance of 4 meters using ETDRS charts. The overall BCVA score was calculated using the BCVA worksheet, which was kept in the source data and the score was recorded in the eCRF.
Time frame: From Baseline to Month 12
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group I | Categorized BCVA Changes at Months 3, 6 and 12 Compared With Baseline for the Study Eye | Gained≥10 letters or reached 84 letters-Month 3 | 97 Participants |
| Group I | Categorized BCVA Changes at Months 3, 6 and 12 Compared With Baseline for the Study Eye | Gained≥15 letters or reached 84 letters-Month 6 | 71 Participants |
| Group I | Categorized BCVA Changes at Months 3, 6 and 12 Compared With Baseline for the Study Eye | Gained≥10 letters or reached 84 letters-Month 6 | 100 Participants |
| Group I | Categorized BCVA Changes at Months 3, 6 and 12 Compared With Baseline for the Study Eye | Gained≥15 letters or reached 84 letters-Month 12 | 81 Participants |
| Group I | Categorized BCVA Changes at Months 3, 6 and 12 Compared With Baseline for the Study Eye | Gained≥15 letters or reached 84 letters-Month 3 | 58 Participants |
| Group I | Categorized BCVA Changes at Months 3, 6 and 12 Compared With Baseline for the Study Eye | Gained≥10 letters or reached 84 letters-Month 12 | 110 Participants |
| Group II | Categorized BCVA Changes at Months 3, 6 and 12 Compared With Baseline for the Study Eye | Gained≥15 letters or reached 84 letters-Month 3 | 59 Participants |
| Group II | Categorized BCVA Changes at Months 3, 6 and 12 Compared With Baseline for the Study Eye | Gained≥10 letters or reached 84 letters-Month 3 | 107 Participants |
| Group II | Categorized BCVA Changes at Months 3, 6 and 12 Compared With Baseline for the Study Eye | Gained≥10 letters or reached 84 letters-Month 6 | 121 Participants |
| Group II | Categorized BCVA Changes at Months 3, 6 and 12 Compared With Baseline for the Study Eye | Gained≥15 letters or reached 84 letters-Month 12 | 75 Participants |
| Group II | Categorized BCVA Changes at Months 3, 6 and 12 Compared With Baseline for the Study Eye | Gained≥15 letters or reached 84 letters-Month 6 | 73 Participants |
| Group II | Categorized BCVA Changes at Months 3, 6 and 12 Compared With Baseline for the Study Eye | Gained≥10 letters or reached 84 letters-Month 12 | 115 Participants |
| Group III | Categorized BCVA Changes at Months 3, 6 and 12 Compared With Baseline for the Study Eye | Gained≥15 letters or reached 84 letters-Month 6 | NA Participants |
| Group III | Categorized BCVA Changes at Months 3, 6 and 12 Compared With Baseline for the Study Eye | Gained≥10 letters or reached 84 letters-Month 6 | NA Participants |
| Group III | Categorized BCVA Changes at Months 3, 6 and 12 Compared With Baseline for the Study Eye | Gained≥10 letters or reached 84 letters-Month 12 | NA Participants |
| Group III | Categorized BCVA Changes at Months 3, 6 and 12 Compared With Baseline for the Study Eye | Gained≥10 letters or reached 84 letters-Month 3 | 24 Participants |
| Group III | Categorized BCVA Changes at Months 3, 6 and 12 Compared With Baseline for the Study Eye | Gained≥15 letters or reached 84 letters-Month 3 | 15 Participants |
| Group III | Categorized BCVA Changes at Months 3, 6 and 12 Compared With Baseline for the Study Eye | Gained≥15 letters or reached 84 letters-Month 12 | NA Participants |
Secondary
Change From Baseline BCVA to the Average Level of BCVA Over All Monthly Assessments From Month 1 to Month 6
Best corrected visual acuity (BCVA) was tested using the early treatment diabetic retinopathy study (ETDRS) VA testing protocol. VA measurements were taken in a sitting position at an initial test distance of 4 meters using ETDRS charts. The overall BCVA score was calculated using the BCVA worksheet, which was kept in the source data and the score was recorded in the eCRF. Between treatment comparison of 0.5 mg ranibizumab intravitreal injections driven by disease activity re-treatment criteria (Group II) versus 0.5 mg ranibizumab intravitreal injections driven by visual acuity stability criteria (Group I) based on the average BCVA change from Baseline to Month 1 through Month 6.
Time frame: From Baseline to Month 6
Population: Full Analysis Set (FAS): Following the intent-to-treat principle, patients were analyzed according to the treatment group they were assigned to at randomization.~FAS, modified last observation carried forward (LOCF), for comparison between ranibizumab treatment groups.): consisted of all patients to whom study treatment were assigned.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I | Change From Baseline BCVA to the Average Level of BCVA Over All Monthly Assessments From Month 1 to Month 6 | Average Month 1 to Month 6 | 64.1 ETDRS letters | Standard Deviation 12.77 |
| Group I | Change From Baseline BCVA to the Average Level of BCVA Over All Monthly Assessments From Month 1 to Month 6 | Baseline | 53.7 ETDRS letters | Standard Deviation 12.65 |
| Group II | Change From Baseline BCVA to the Average Level of BCVA Over All Monthly Assessments From Month 1 to Month 6 | Average Month 1 to Month 6 | 64.9 ETDRS letters | Standard Deviation 13.14 |
| Group II | Change From Baseline BCVA to the Average Level of BCVA Over All Monthly Assessments From Month 1 to Month 6 | Baseline | 54.2 ETDRS letters | Standard Deviation 13.01 |
| Group III | Change From Baseline BCVA to the Average Level of BCVA Over All Monthly Assessments From Month 1 to Month 6 | Baseline | 52.6 ETDRS letters | Standard Deviation 12.29 |
| Group III | Change From Baseline BCVA to the Average Level of BCVA Over All Monthly Assessments From Month 1 to Month 6 | Average Month 1 to Month 6 | 59.6 ETDRS letters | Standard Deviation 12.99 |
p-value: <0.00195% CI: [-1.3, 2.1]Cochran-Mantel-Haenszel
Secondary
Mean Change From Baseline in Visual Acuity Over Time
Best corrected visual acuity (BCVA) was tested using the ETDRS VA testing protocol. VA measurements were taken in a sitting position at an initial test distance of 4 meters using ETDRS charts. The overall BCVA score was calculated using the BCVA worksheet, which was kept in the source data and the score was recorded in the eCRF.
Time frame: Change from baseline at months 3, 6, and 12
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I | Mean Change From Baseline in Visual Acuity Over Time | Month 12 | 12.0 ETDRS letters | Standard Deviation 11.5 |
| Group I | Mean Change From Baseline in Visual Acuity Over Time | Month 3 | 10.5 ETDRS letters | Standard Deviation 9.13 |
| Group I | Mean Change From Baseline in Visual Acuity Over Time | Month 6 | 11.6 ETDRS letters | Standard Deviation 10.66 |
| Group II | Mean Change From Baseline in Visual Acuity Over Time | Month 12 | 13.1 ETDRS letters | Standard Deviation 11.46 |
| Group II | Mean Change From Baseline in Visual Acuity Over Time | Month 6 | 12.1 ETDRS letters | Standard Deviation 11.57 |
| Group II | Mean Change From Baseline in Visual Acuity Over Time | Month 3 | 10.8 ETDRS letters | Standard Deviation 10.09 |
| Group III | Mean Change From Baseline in Visual Acuity Over Time | Month 12 | 10.3 ETDRS letters | Standard Deviation 12.69 |
| Group III | Mean Change From Baseline in Visual Acuity Over Time | Month 6 | 9.5 ETDRS letters | Standard Deviation 10.5 |
| Group III | Mean Change From Baseline in Visual Acuity Over Time | Month 3 | 4.5 ETDRS letters | Standard Deviation 9.35 |
Secondary
Mean Change From Baseline Over Time in Central Sub-field Thickness (CSFT)
Central sub-field thickness (CSFT) is a variable assessed via Optical Coherence Tomography (OCT). OCT was performed prior to any study drug administration to assess presence of intra, subretinal fluid, or increase of CSFT.
Time frame: Baseline, Month 3, Month 6, and Month 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I | Mean Change From Baseline Over Time in Central Sub-field Thickness (CSFT) | Month 12 | -79.4 micrometer | Standard Deviation 71.39 |
| Group I | Mean Change From Baseline Over Time in Central Sub-field Thickness (CSFT) | Month 3 | -66.4 micrometer | Standard Deviation 98.68 |
| Group I | Mean Change From Baseline Over Time in Central Sub-field Thickness (CSFT) | Month 6 | -70.7 micrometer | Standard Deviation 73.2 |
| Group II | Mean Change From Baseline Over Time in Central Sub-field Thickness (CSFT) | Month 12 | -80.8 micrometer | Standard Deviation 85.93 |
| Group II | Mean Change From Baseline Over Time in Central Sub-field Thickness (CSFT) | Month 6 | -75.1 micrometer | Standard Deviation 80.9 |
| Group II | Mean Change From Baseline Over Time in Central Sub-field Thickness (CSFT) | Month 3 | -71.2 micrometer | Standard Deviation 81.28 |
| Group III | Mean Change From Baseline Over Time in Central Sub-field Thickness (CSFT) | Month 12 | -66.0 micrometer | Standard Deviation 93.6 |
| Group III | Mean Change From Baseline Over Time in Central Sub-field Thickness (CSFT) | Month 6 | -59.3 micrometer | Standard Deviation 81.82 |
| Group III | Mean Change From Baseline Over Time in Central Sub-field Thickness (CSFT) | Month 3 | -29.1 micrometer | Standard Deviation 75.57 |
Secondary
NEI-VFQ-25 - Change From Baseline to Month 3, 6 and 12
The VFQ-25 consists of 25 vision related questions across 11 vision related subscales, including general vision, ocular pain, near activities, distance activities, social function, mental health, role difficulties, dependency, driving, color vision and peripheral vision, and a general health rating. Items are converted to a 0-100 scale on each subscale and for the composite score where higher scores represents better functioning.
Time frame: Change from baseline at month 3, 6 and 12
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I | NEI-VFQ-25 - Change From Baseline to Month 3, 6 and 12 | Month 3 | 4.7 Composite score | Standard Deviation 12.28 |
| Group I | NEI-VFQ-25 - Change From Baseline to Month 3, 6 and 12 | Month 6 | 5.0 Composite score | Standard Deviation 13.4 |
| Group I | NEI-VFQ-25 - Change From Baseline to Month 3, 6 and 12 | Month 12 | 4.4 Composite score | Standard Deviation 16.03 |
| Group II | NEI-VFQ-25 - Change From Baseline to Month 3, 6 and 12 | Month 6 | 5.6 Composite score | Standard Deviation 15.42 |
| Group II | NEI-VFQ-25 - Change From Baseline to Month 3, 6 and 12 | Month 12 | 4.7 Composite score | Standard Deviation 16.92 |
| Group II | NEI-VFQ-25 - Change From Baseline to Month 3, 6 and 12 | Month 3 | 6.1 Composite score | Standard Deviation 13.49 |
| Group III | NEI-VFQ-25 - Change From Baseline to Month 3, 6 and 12 | Month 12 | 1.3 Composite score | Standard Deviation 16.85 |
| Group III | NEI-VFQ-25 - Change From Baseline to Month 3, 6 and 12 | Month 3 | 1.7 Composite score | Standard Deviation 13.55 |
| Group III | NEI-VFQ-25 - Change From Baseline to Month 3, 6 and 12 | Month 6 | -0.1 Composite score | Standard Deviation 15.3 |
Secondary
Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12
CNV leakage is assessed via fluorescein angiography (center involvement) category: definite, questionable, absent, can't grade, and missing.
Time frame: From Baseline until Month 12
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group I | Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12 | Baseline - Questionable | 1 Participants |
| Group I | Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12 | Month 12 - Questionable | 6 Participants |
| Group I | Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12 | Month 12 - Absent | 133 Participants |
| Group I | Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12 | Baseline - Definite | 164 Participants |
| Group I | Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12 | Baseline - Missing | 1 Participants |
| Group I | Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12 | Month 12 - Missing | 7 Participants |
| Group I | Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12 | Baseline - Can't Grade | 2 Participants |
| Group I | Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12 | Baseline - Absent | 14 Participants |
| Group I | Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12 | Month 12 - Definite | 34 Participants |
| Group I | Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12 | Month 12 - Can't Grade | 2 Participants |
| Group II | Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12 | Baseline - Absent | 19 Participants |
| Group II | Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12 | Baseline - Can't Grade | 0 Participants |
| Group II | Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12 | Baseline - Missing | 2 Participants |
| Group II | Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12 | Month 12 - Definite | 43 Participants |
| Group II | Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12 | Month 12 - Questionable | 4 Participants |
| Group II | Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12 | Month 12 - Can't Grade | 2 Participants |
| Group II | Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12 | Month 12 - Missing | 6 Participants |
| Group II | Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12 | Baseline - Definite | 160 Participants |
| Group II | Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12 | Baseline - Questionable | 3 Participants |
| Group II | Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12 | Month 12 - Absent | 129 Participants |
| Group III | Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12 | Baseline - Absent | 13 Participants |
| Group III | Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12 | Baseline - Definite | 76 Participants |
| Group III | Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12 | Month 12 - Definite | 26 Participants |
| Group III | Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12 | Month 12 - Absent | 56 Participants |
| Group III | Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12 | Baseline - Questionable | 0 Participants |
| Group III | Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12 | Baseline - Missing | 2 Participants |
| Group III | Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12 | Month 12 - Can't Grade | 0 Participants |
| Group III | Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12 | Baseline - Can't Grade | 0 Participants |
| Group III | Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12 | Month 12 - Missing | 7 Participants |
| Group III | Number of Patients With CNV Leakage (Center Involvement) in the Study Eye at Baseline and Month 12 | Month 12 - Questionable | 2 Participants |
Secondary
Number of Ranibizumab Injections Received in the Study Eye for the Ranibizumab Groups
To assess treatment pattern with ranibizumab
Time frame: From Baseline to Month 12
Population: Safety Set: all patients who received at least one application of study treatment \& had at least one post-Baseline safety assessment. Patients were analyzed according to treatment received. One patient randomized to vPDT Group III received one ranibizumab injection prior to Month 3; this patient was analyzed under Group II in Safety Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I | Number of Ranibizumab Injections Received in the Study Eye for the Ranibizumab Groups | Month 3 | 2.4 Injections | Standard Deviation 0.53 |
| Group I | Number of Ranibizumab Injections Received in the Study Eye for the Ranibizumab Groups | Month 12 | 4.6 Injections | Standard Deviation 2.44 |
| Group II | Number of Ranibizumab Injections Received in the Study Eye for the Ranibizumab Groups | Month 12 | 3.9 Injections | Standard Deviation 2.5 |
| Group II | Number of Ranibizumab Injections Received in the Study Eye for the Ranibizumab Groups | Month 3 | 2.1 Injections | Standard Deviation 0.84 |
| Group III | Number of Ranibizumab Injections Received in the Study Eye for the Ranibizumab Groups | Month 3 | NA Injections | — |
| Group III | Number of Ranibizumab Injections Received in the Study Eye for the Ranibizumab Groups | Month 12 | 3.2 Injections | Standard Deviation 2.25 |
| Group III Without 0.5mg Ranibizumab | Number of Ranibizumab Injections Received in the Study Eye for the Ranibizumab Groups | Month 3 | NA Injections | — |
| Group III Without 0.5mg Ranibizumab | Number of Ranibizumab Injections Received in the Study Eye for the Ranibizumab Groups | Month 12 | 3.8 Injections | Standard Deviation 2.36 |
Secondary
The Average Change in BCVA Score From Baseline to Month 1 Through Month 12
Best corrected visual acuity (BCVA) was tested using the ETDRS VA testing protocol. VA measurements were taken in a sitting position at an initial test distance of 4 meters using ETDRS charts. The overall BCVA score was calculated using the BCVA worksheet, which was kept in the source data and the score was recorded in the eCRF. Between treatment comparison of 0.5 mg ranibizumab intravitreal injections driven by disease activity re-treatment criteria (Group II) versus 0.5 mg ranibizumab intravitreal injections driven by visual acuity stability criteria (Group I) based on the average BCVA change from Baseline to Month 1 through Month 12
Time frame: From Baseline to Month 12
Population: FAS, modified LOCF for comparison between ranibizumab treatment groups.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I | The Average Change in BCVA Score From Baseline to Month 1 Through Month 12 | Baseline | 53.7 ETDRS letters | Standard Deviation 12.65 |
| Group I | The Average Change in BCVA Score From Baseline to Month 1 Through Month 12 | Average Month 1 to Month 12 | 64.8 ETDRS letters | Standard Deviation 12.82 |
| Group II | The Average Change in BCVA Score From Baseline to Month 1 Through Month 12 | Baseline | 54.2 ETDRS letters | Standard Deviation 13.01 |
| Group II | The Average Change in BCVA Score From Baseline to Month 1 Through Month 12 | Average Month 1 to Month 12 | 65.9 ETDRS letters | Standard Deviation 13.26 |
| Group III | The Average Change in BCVA Score From Baseline to Month 1 Through Month 12 | Baseline | 52.6 ETDRS letters | Standard Deviation 12.29 |
| Group III | The Average Change in BCVA Score From Baseline to Month 1 Through Month 12 | Average Month 1 to Month 12 | 61.2 ETDRS letters | Standard Deviation 13.1 |