Subfoveal Choroidal Neovascularization(CNV) Secondary to Age-related Macular Degeneration (AMD)
Conditions
Keywords
Subfoveal CNV, AMD, ranibizumab
Brief summary
Open-label Multicenter, Phase I/II Study comprising three phases (single dose, multiple dose and extension phase), Assessing the Safety and Efficacy of Ranibizumab (RFB002) in Japanese Patients With Subfoveal Choroidal Neovascularization (CNV) Secondary to Age-related Macular Degeneration (AMD).
Detailed description
The safety and tolerability of single intravitreal injections of ranibizumab was evaluated in patients enrolled in the single dose phase (Group A). Patients who successfully completed the single dose phase (i.e. did not experience a grade-3 targeted adverse event) could enter the multiple dose phase and receive ranibizumab injections for an additional 11 months. Simultaneously, the multiple dose phase was initiated in two parallel dose groups of additional patients (Group B), who received ranibizumab injections for 12 months. After patients in Group A and Group B had completed the multiple dose phase, all patients who provided written consent and were considered eligible based on the inclusion and exclusion criteria of the extension phase had the opportunity to continue on study treatment with the individualized flexible treatment regimen guided by monthly acuity scores and other ophthalmic examinations until approval of ranibizumab in Japan.
Interventions
DRUGRanibizumab
Ranibizumab was administered by intravitreal injection in the study eye. Intravitreal injection was performed by the investigator following slitlamp examination.
Sponsors
Novartis
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 or greater 2. Patients with primary or recurrent subfoveal CNV secondary to AMD 3. Patients who have a BCVA score between 73 and 24 letters in the study eye using ETDRS-like grading charts (approximately 20/40 to 20/320)
Exclusion criteria
1\. No prior treatment in the study eye with verteporfin, external-beam radiation therapy, subfoveal focal laser photocoagulation, vitrectomy, or transpupillary thermotherapy Extension Phase Inclusion criteria: 1. Personally provided written informed consent to participate in the extension phase. 2. Patients with subfoveal CNV secondary to AMD who had completed the multiple dose phase in either of the ranibizumab groups (Group A or B). 3. Patients could participate in the extension phase even if they failed to do so on the day of the exit visit in the multiple dose phase (Group A and B), regardless of the time elapsed until the participation in the extension phase.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in the Best Corrected Visual Acuity Score of the Study Eye at Month 6 in Group B | Baseline and Month 6 | The efficacy assessment was based on Group B patients. Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 2 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a starting test distance of 2 meters. The BCVA score is the number of letters read correctly by the patient, hence an increase in score indicates improvement in acuity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Month 6 and Month 12 in Group B | Baseline, Month 6 and Month 12 | BCVA measurements were taken in a sitting position using best correction determined from protocol refraction and ETDRS-like visual acuity testing charts at a starting test distance of 2 meters. |
| Extension Phase: Mean Change From Month 12 (Start of Extension Phase) in Best Corrected Visual Acuity Score of the Study Eye at Last Visit of Extension Phase in Group B. | Month 12 (start of extension phase) and last visit of extension phase. Duration in the extension phase varied depending on the study entry. The mean duration of treatment was 1.45 years in the 0.3 mg group and 1.36 years in the 0.5 mg dose group. | Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 2 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a starting test distance of 2 meters. The BCVA score is the number of letters read correctly by the patient, hence an increase in score indicates improvement in acuity. |
| Extension Phase: Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Last Visit of Extension Phase in Group B | Baseline and last visit of extension phase - Duration in the extension phase varied depending on the study entry. The mean duration of treatment was 1.45 years in the 0.3 mg group and 1.36 years in the 0.5 mg dose group. | BCVA measurements were taken in a sitting position using best correction determined from protocol refraction and ETDRS-like visual acuity testing charts at a starting test distance of 2 meters. The following categories were evaluated: * Participants with a BCVA score loss of fewer than 15 letters from baseline at Last Visit * Participants with a BCVA score loss of 30 or more letters from baseline at Last Visit * Participants with a BCVA score gain of 15 or more letters from baseline at Last Visit * Participants with a BCVA score of less than 34 letters at Last Visit |
| Mean Change From Baseline in Total Area of Choroidal Neovascularization of the Study Eye in Group B | Baseline, Months 3, 6, 9 and 12 | Choroidal Neovascularization was assessed by fluorescein angiography in conjunction with color fundus photography. Analysis was performed by the central reading center. The area of Choroidal Neovascularization is expressed as Macular Photocoagulation Study standard Disc Areas (DA; equivalent to 2.54 mm\^2 on the retina). |
| Mean Change From Baseline in the Best Corrected Visual Acuity Score of the Study Eye at Month 12 in Group B | Baseline and Month 12 | The efficacy assessment was based on Group B patients. BCVA was assessed during all study visits using best correction determined from protocol refraction and ETDRS-like visual acuity testing charts at a starting test distance of 2 meters. The BCVA score is the number of letters read correctly by the patient, hence an increase in score indicates improvement in acuity. |
| Percentage of Participants in Group B With Absence of Leakage in the Study Eye at Month 3, 6, 9 and 12. | Months 3, 6, 9 and 12 | Area of leakage was assessed by fluorescein angiography in conjunction with color fundus photography. Analysis was performed at the central reading center. |
| Mean Change From Baseline in Foveal Retinal Thickness of the Study Eye in Group B | Baseline, Months 3, 6, 9 and 12 | Foveal retinal thickness was assessed by Optical Coherence Tomography (OCT) at a subset of the study sites and was analyzed by the central reading center. |
| Mean Change From Baseline in Total Retinal Volume of the Study Eye in Group B | Baseline, Months 3, 6, 9 and 12 | Total retinal volume was assessed by Optical Coherence tomography (OCT) at a subset of the study sites and was analyzed by the central reading center. |
| Mean Change From Baseline in Total Area of Leakage From CNV Plus Staining of Retinal Pigment Epithelium of the Study Eye in Group B | Baseline, Months 3, 6, 9 and 12 | Area of leakage from CNV plus staining of retinal pigment epithelium was assessed by fluorescein angiography in conjunction with color fundus photography. Analysis was performed by the central reading center. The total area is expressed as Macular Photocoagulation Study standard Disc Areas (DA; equivalent to 2.54 mm\^2 on the retina). |
Countries
Japan
Participant flow
Pre-assignment details
In total, 88 patients were enrolled in the study, 12 in Group A and 76 in Group B. The single dose phase of the study (Group A patients only) was completed prior to initiation of the multiple dose phase (Groups A and B).
Participants by arm
| Arm | Count |
|---|---|
| Group A: Ranibizumab 0.3 mg In the single dose phase, all patients randomized in Group A received a single intravitreal injection of 0.3 mg of ranibizumab into the study eye. Those patients who successfully completed this phase entered the multiple dose phase, where they received an intravitreal injection of 0.3 mg of ranibizumab once a month for an additional 11 months. Subsequently patients enrolling in the extension phase received an intravitreal injection of 0.3 mg of ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.70 years. | 6 |
| Group A: Ranibizumab 0.5 mg In the single dose phase, all patients randomized in Group A received a single intravitreal injection of 0.5 mg of ranibizumab into the study eye. Those patients who successfully completed this phase entered the multiple dose phase, where they received an intravitreal injection of 0.5 mg of ranibizumab once a month for an additional 11 months. Subsequently Group A patients enrolling in the extension phase received an intravitreal injection of 0.5 mg of ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.93 years. | 6 |
| Group B: Ranibizumab 0.3 mg Group B patients received a total of 12 monthly intravitreal injections of 0.3 mg of ranibizumab into the study eye in the multiple dose phase of the study. Group B patients enrolled in the extension phase received an intravitreal injection of 0.3 mg of ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.45 years. | 35 |
| Group B: Ranibizumab 0.5 mg Group B patients received a total of 12 monthly intravitreal injections of 0.5 mg of ranibizumab into the study eye in the multiple dose phase of the study. Group B patients who enrolled in the extension phase received an intravitreal injection of 0.5 mg of ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.36 years. | 41 |
| Total | 88 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Extension Phase | Adverse Event | 0 | 0 | 2 | 2 |
| Extension Phase | condition no longer requires study drug | 2 | 0 | 2 | 7 |
| Extension Phase | Protocol Violation | 0 | 0 | 1 | 0 |
| Extension Phase | Withdrawal by Subject | 0 | 0 | 1 | 3 |
| Multiple Dose Phase | Adverse Event | 1 | 0 | 1 | 1 |
| Multiple Dose Phase | Death | 0 | 0 | 1 | 1 |
| Multiple Dose Phase | Protocol Violation | 0 | 0 | 1 | 0 |
| Multiple Dose Phase | Withdrawal by Subject | 0 | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | Group A: Ranibizumab 0.3 mg | Group A: Ranibizumab 0.5 mg | Group B: Ranibizumab 0.3 mg | Group B: Ranibizumab 0.5 mg | Total |
|---|---|---|---|---|---|
| Age, Customized 50 to <65 years | 2 Participants | 0 Participants | 8 Participants | 10 Participants | 20 Participants |
| Age, Customized 65 to <75 years | 1 Participants | 4 Participants | 16 Participants | 13 Participants | 35 Participants |
| Age, Customized 75 to <85 years | 2 Participants | 2 Participants | 6 Participants | 12 Participants | 21 Participants |
| Age, Customized >= 85 years | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 4 Participants |
| Gender Female | 0 participants | 1 participants | 9 participants | 5 participants | 15 participants |
| Gender Male | 3 participants | 5 participants | 19 participants | 28 participants | 55 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 9 Participants | 8 Participants | 19 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 26 Participants | 33 Participants | 69 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 | 38 / 41 | 43 / 47 | 27 / 31 | 28 / 39 |
| serious Total, serious adverse events | 5 / 41 | 8 / 47 | 5 / 31 | 8 / 39 |
Outcome results
Primary
Mean Change From Baseline in the Best Corrected Visual Acuity Score of the Study Eye at Month 6 in Group B
The efficacy assessment was based on Group B patients. Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 2 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a starting test distance of 2 meters. The BCVA score is the number of letters read correctly by the patient, hence an increase in score indicates improvement in acuity.
Time frame: Baseline and Month 6
Population: Intent-to treat (ITT) population for Group B patients consisted of all patients randomized in Group B that received at least one dose of study drug and had at least one post-baseline assessment of the primary efficacy variable. The Last Observation Carried Forward (LOCF) was used to impute missing data at month 6 in the ITT analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group B: Ranibizumab 0.3 mg | Mean Change From Baseline in the Best Corrected Visual Acuity Score of the Study Eye at Month 6 in Group B | Baseline | 47.6 Number of Letters | Standard Deviation 11.82 |
| Group B: Ranibizumab 0.3 mg | Mean Change From Baseline in the Best Corrected Visual Acuity Score of the Study Eye at Month 6 in Group B | Month 6 | 55.7 Number of Letters | Standard Deviation 13.16 |
| Group B: Ranibizumab 0.3 mg | Mean Change From Baseline in the Best Corrected Visual Acuity Score of the Study Eye at Month 6 in Group B | Change from Baseline | 8.1 Number of Letters | Standard Deviation 12.65 |
| Group B: Ranibizumab 0.5 mg | Mean Change From Baseline in the Best Corrected Visual Acuity Score of the Study Eye at Month 6 in Group B | Baseline | 48.1 Number of Letters | Standard Deviation 10.75 |
| Group B: Ranibizumab 0.5 mg | Mean Change From Baseline in the Best Corrected Visual Acuity Score of the Study Eye at Month 6 in Group B | Month 6 | 57.1 Number of Letters | Standard Deviation 14.99 |
| Group B: Ranibizumab 0.5 mg | Mean Change From Baseline in the Best Corrected Visual Acuity Score of the Study Eye at Month 6 in Group B | Change from Baseline | 9.0 Number of Letters | Standard Deviation 9.62 |
Secondary
Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Month 6 and Month 12 in Group B
BCVA measurements were taken in a sitting position using best correction determined from protocol refraction and ETDRS-like visual acuity testing charts at a starting test distance of 2 meters.
Time frame: Baseline, Month 6 and Month 12
Population: ITT population, using LOCF.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group B: Ranibizumab 0.3 mg | Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Month 6 and Month 12 in Group B | Loss of < 15 letters from Baseline at month 6 | 34 Participants |
| Group B: Ranibizumab 0.3 mg | Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Month 6 and Month 12 in Group B | Loss of < 15 letters from Baseline at month 12 | 34 Participants |
| Group B: Ranibizumab 0.3 mg | Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Month 6 and Month 12 in Group B | Gain of ≥15 letters from Baseline at month 6 | 12 Participants |
| Group B: Ranibizumab 0.3 mg | Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Month 6 and Month 12 in Group B | Gain of ≥15 letters from Baseline at month 12 | 13 Participants |
| Group B: Ranibizumab 0.3 mg | Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Month 6 and Month 12 in Group B | Loss of ≥30 letters from Baseline at month 6 | 0 Participants |
| Group B: Ranibizumab 0.3 mg | Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Month 6 and Month 12 in Group B | Loss of ≥30 letters from Baseline at month 12 | 0 Participants |
| Group B: Ranibizumab 0.3 mg | Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Month 6 and Month 12 in Group B | Visual acuity < 34 letters at Month 6 | 2 Participants |
| Group B: Ranibizumab 0.3 mg | Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Month 6 and Month 12 in Group B | Visual acuity < 34 letters at Month 12 | 2 Participants |
| Group B: Ranibizumab 0.5 mg | Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Month 6 and Month 12 in Group B | Visual acuity < 34 letters at Month 12 | 1 Participants |
| Group B: Ranibizumab 0.5 mg | Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Month 6 and Month 12 in Group B | Loss of < 15 letters from Baseline at month 6 | 41 Participants |
| Group B: Ranibizumab 0.5 mg | Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Month 6 and Month 12 in Group B | Loss of ≥30 letters from Baseline at month 6 | 0 Participants |
| Group B: Ranibizumab 0.5 mg | Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Month 6 and Month 12 in Group B | Loss of < 15 letters from Baseline at month 12 | 41 Participants |
| Group B: Ranibizumab 0.5 mg | Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Month 6 and Month 12 in Group B | Visual acuity < 34 letters at Month 6 | 2 Participants |
| Group B: Ranibizumab 0.5 mg | Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Month 6 and Month 12 in Group B | Gain of ≥15 letters from Baseline at month 6 | 10 Participants |
| Group B: Ranibizumab 0.5 mg | Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Month 6 and Month 12 in Group B | Loss of ≥30 letters from Baseline at month 12 | 0 Participants |
| Group B: Ranibizumab 0.5 mg | Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Month 6 and Month 12 in Group B | Gain of ≥15 letters from Baseline at month 12 | 13 Participants |
Secondary
Extension Phase: Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Last Visit of Extension Phase in Group B
BCVA measurements were taken in a sitting position using best correction determined from protocol refraction and ETDRS-like visual acuity testing charts at a starting test distance of 2 meters. The following categories were evaluated: * Participants with a BCVA score loss of fewer than 15 letters from baseline at Last Visit * Participants with a BCVA score loss of 30 or more letters from baseline at Last Visit * Participants with a BCVA score gain of 15 or more letters from baseline at Last Visit * Participants with a BCVA score of less than 34 letters at Last Visit
Time frame: Baseline and last visit of extension phase - Duration in the extension phase varied depending on the study entry. The mean duration of treatment was 1.45 years in the 0.3 mg group and 1.36 years in the 0.5 mg dose group.
Population: Includes patients enrolled in the extension phase, observed data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group B: Ranibizumab 0.3 mg | Extension Phase: Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Last Visit of Extension Phase in Group B | Loss of < 15 letters from Baseline | 24 Participants |
| Group B: Ranibizumab 0.3 mg | Extension Phase: Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Last Visit of Extension Phase in Group B | Gain of ≥15 letters from Baseline | 9 Participants |
| Group B: Ranibizumab 0.3 mg | Extension Phase: Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Last Visit of Extension Phase in Group B | Loss of ≥30 letters from Baseline | 1 Participants |
| Group B: Ranibizumab 0.3 mg | Extension Phase: Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Last Visit of Extension Phase in Group B | Visual acuity < 34 letters | 3 Participants |
| Group B: Ranibizumab 0.5 mg | Extension Phase: Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Last Visit of Extension Phase in Group B | Visual acuity < 34 letters | 1 Participants |
| Group B: Ranibizumab 0.5 mg | Extension Phase: Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Last Visit of Extension Phase in Group B | Loss of < 15 letters from Baseline | 32 Participants |
| Group B: Ranibizumab 0.5 mg | Extension Phase: Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Last Visit of Extension Phase in Group B | Loss of ≥30 letters from Baseline | 1 Participants |
| Group B: Ranibizumab 0.5 mg | Extension Phase: Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Last Visit of Extension Phase in Group B | Gain of ≥15 letters from Baseline | 9 Participants |
Secondary
Extension Phase: Mean Change From Month 12 (Start of Extension Phase) in Best Corrected Visual Acuity Score of the Study Eye at Last Visit of Extension Phase in Group B.
Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 2 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a starting test distance of 2 meters. The BCVA score is the number of letters read correctly by the patient, hence an increase in score indicates improvement in acuity.
Time frame: Month 12 (start of extension phase) and last visit of extension phase. Duration in the extension phase varied depending on the study entry. The mean duration of treatment was 1.45 years in the 0.3 mg group and 1.36 years in the 0.5 mg dose group.
Population: The analysis population included all enrolled patients in the extension phase. For the analysis of the results of the extension phase, all data are presented as observed. Patients must have values both at Month 12 and Last Visit to be included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group B: Ranibizumab 0.3 mg | Extension Phase: Mean Change From Month 12 (Start of Extension Phase) in Best Corrected Visual Acuity Score of the Study Eye at Last Visit of Extension Phase in Group B. | Baseline | 47.9 Letters | Standard Deviation 12.59 |
| Group B: Ranibizumab 0.3 mg | Extension Phase: Mean Change From Month 12 (Start of Extension Phase) in Best Corrected Visual Acuity Score of the Study Eye at Last Visit of Extension Phase in Group B. | Last visit | 55.4 Letters | Standard Deviation 17.14 |
| Group B: Ranibizumab 0.3 mg | Extension Phase: Mean Change From Month 12 (Start of Extension Phase) in Best Corrected Visual Acuity Score of the Study Eye at Last Visit of Extension Phase in Group B. | Month 12 | 59.1 Letters | Standard Deviation 11.69 |
| Group B: Ranibizumab 0.3 mg | Extension Phase: Mean Change From Month 12 (Start of Extension Phase) in Best Corrected Visual Acuity Score of the Study Eye at Last Visit of Extension Phase in Group B. | Change from Month 12 | -3.6 Letters | Standard Deviation 14.82 |
| Group B: Ranibizumab 0.5 mg | Extension Phase: Mean Change From Month 12 (Start of Extension Phase) in Best Corrected Visual Acuity Score of the Study Eye at Last Visit of Extension Phase in Group B. | Change from Month 12 | -2.2 Letters | Standard Deviation 7.92 |
| Group B: Ranibizumab 0.5 mg | Extension Phase: Mean Change From Month 12 (Start of Extension Phase) in Best Corrected Visual Acuity Score of the Study Eye at Last Visit of Extension Phase in Group B. | Baseline | 50.0 Letters | Standard Deviation 10.38 |
| Group B: Ranibizumab 0.5 mg | Extension Phase: Mean Change From Month 12 (Start of Extension Phase) in Best Corrected Visual Acuity Score of the Study Eye at Last Visit of Extension Phase in Group B. | Month 12 | 59.8 Letters | Standard Deviation 15.07 |
| Group B: Ranibizumab 0.5 mg | Extension Phase: Mean Change From Month 12 (Start of Extension Phase) in Best Corrected Visual Acuity Score of the Study Eye at Last Visit of Extension Phase in Group B. | Last visit | 57.6 Letters | Standard Deviation 15.36 |
Secondary
Mean Change From Baseline in Foveal Retinal Thickness of the Study Eye in Group B
Foveal retinal thickness was assessed by Optical Coherence Tomography (OCT) at a subset of the study sites and was analyzed by the central reading center.
Time frame: Baseline, Months 3, 6, 9 and 12
Population: The analysis includes Group B Intent-to treat (ITT) population, observed data. OCT was performed in a total of 58 patients at selected sites.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group B: Ranibizumab 0.3 mg | Mean Change From Baseline in Foveal Retinal Thickness of the Study Eye in Group B | Mean change from Baseline at Month 3 [N=27, 29] | -124.4 micrometers | Standard Deviation 141.6 |
| Group B: Ranibizumab 0.3 mg | Mean Change From Baseline in Foveal Retinal Thickness of the Study Eye in Group B | Mean change from Baseline at Month 9 [N=26, 27] | -188.4 micrometers | Standard Deviation 190.1 |
| Group B: Ranibizumab 0.3 mg | Mean Change From Baseline in Foveal Retinal Thickness of the Study Eye in Group B | Mean change from Baseline at Month 6 [N=26, 28] | -142.9 micrometers | Standard Deviation 199.3 |
| Group B: Ranibizumab 0.3 mg | Mean Change From Baseline in Foveal Retinal Thickness of the Study Eye in Group B | Mean change from Baseline at Month 12 [N=26, 26] | -194.0 micrometers | Standard Deviation 199.8 |
| Group B: Ranibizumab 0.3 mg | Mean Change From Baseline in Foveal Retinal Thickness of the Study Eye in Group B | Baseline [N=28, 30] | 336.7 micrometers | Standard Deviation 195.3 |
| Group B: Ranibizumab 0.5 mg | Mean Change From Baseline in Foveal Retinal Thickness of the Study Eye in Group B | Mean change from Baseline at Month 12 [N=26, 26] | -257.8 micrometers | Standard Deviation 209.8 |
| Group B: Ranibizumab 0.5 mg | Mean Change From Baseline in Foveal Retinal Thickness of the Study Eye in Group B | Baseline [N=28, 30] | 370.7 micrometers | Standard Deviation 171.9 |
| Group B: Ranibizumab 0.5 mg | Mean Change From Baseline in Foveal Retinal Thickness of the Study Eye in Group B | Mean change from Baseline at Month 3 [N=27, 29] | -195.6 micrometers | Standard Deviation 187.5 |
| Group B: Ranibizumab 0.5 mg | Mean Change From Baseline in Foveal Retinal Thickness of the Study Eye in Group B | Mean change from Baseline at Month 6 [N=26, 28] | -225.6 micrometers | Standard Deviation 192.2 |
| Group B: Ranibizumab 0.5 mg | Mean Change From Baseline in Foveal Retinal Thickness of the Study Eye in Group B | Mean change from Baseline at Month 9 [N=26, 27] | -245.4 micrometers | Standard Deviation 203.1 |
Secondary
Mean Change From Baseline in the Best Corrected Visual Acuity Score of the Study Eye at Month 12 in Group B
The efficacy assessment was based on Group B patients. BCVA was assessed during all study visits using best correction determined from protocol refraction and ETDRS-like visual acuity testing charts at a starting test distance of 2 meters. The BCVA score is the number of letters read correctly by the patient, hence an increase in score indicates improvement in acuity.
Time frame: Baseline and Month 12
Population: Intent-to treat (ITT) population for Group B patients consisted of all patients randomized in Group B that received at least one dose of study drug and had at least one post-baseline assessment of the efficacy variable. The Last Observation carried Forward (LOCF) was used to impute missing data at month 12 in the ITT analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group B: Ranibizumab 0.3 mg | Mean Change From Baseline in the Best Corrected Visual Acuity Score of the Study Eye at Month 12 in Group B | Baseline | 47.6 Number of Letters | Standard Deviation 11.82 |
| Group B: Ranibizumab 0.3 mg | Mean Change From Baseline in the Best Corrected Visual Acuity Score of the Study Eye at Month 12 in Group B | Month 12 | 57.1 Number of Letters | Standard Deviation 12.91 |
| Group B: Ranibizumab 0.3 mg | Mean Change From Baseline in the Best Corrected Visual Acuity Score of the Study Eye at Month 12 in Group B | Change from Baseline | 9.5 Number of Letters | Standard Deviation 12.79 |
| Group B: Ranibizumab 0.5 mg | Mean Change From Baseline in the Best Corrected Visual Acuity Score of the Study Eye at Month 12 in Group B | Baseline | 48.1 Number of Letters | Standard Deviation 10.75 |
| Group B: Ranibizumab 0.5 mg | Mean Change From Baseline in the Best Corrected Visual Acuity Score of the Study Eye at Month 12 in Group B | Month 12 | 58.6 Number of Letters | Standard Deviation 15.44 |
| Group B: Ranibizumab 0.5 mg | Mean Change From Baseline in the Best Corrected Visual Acuity Score of the Study Eye at Month 12 in Group B | Change from Baseline | 10.5 Number of Letters | Standard Deviation 11.14 |
Secondary
Mean Change From Baseline in Total Area of Choroidal Neovascularization of the Study Eye in Group B
Choroidal Neovascularization was assessed by fluorescein angiography in conjunction with color fundus photography. Analysis was performed by the central reading center. The area of Choroidal Neovascularization is expressed as Macular Photocoagulation Study standard Disc Areas (DA; equivalent to 2.54 mm\^2 on the retina).
Time frame: Baseline, Months 3, 6, 9 and 12
Population: Intent-to treat (ITT) population for Group B patients consisted of all patients randomized in Group B that received at least one dose of study drug and had at least one post-baseline assessment. The Last Observation Carried Forward (LOCF) was used to impute missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group B: Ranibizumab 0.3 mg | Mean Change From Baseline in Total Area of Choroidal Neovascularization of the Study Eye in Group B | Mean change from Baseline at Month 3 [N=34, 40] | -0.10 disc areas | Standard Deviation 0.95 |
| Group B: Ranibizumab 0.3 mg | Mean Change From Baseline in Total Area of Choroidal Neovascularization of the Study Eye in Group B | Mean change from Baseline at Month 9 [N=34, 40] | -0.23 disc areas | Standard Deviation 0.97 |
| Group B: Ranibizumab 0.3 mg | Mean Change From Baseline in Total Area of Choroidal Neovascularization of the Study Eye in Group B | Mean change from Baseline at Month 6 [N=34, 40] | -0.15 disc areas | Standard Deviation 0.97 |
| Group B: Ranibizumab 0.3 mg | Mean Change From Baseline in Total Area of Choroidal Neovascularization of the Study Eye in Group B | Mean change from Baseline at Month 12 [N=34, 40] | -0.16 disc areas | Standard Deviation 1.01 |
| Group B: Ranibizumab 0.3 mg | Mean Change From Baseline in Total Area of Choroidal Neovascularization of the Study Eye in Group B | Baseline [N=35, 41] | 2.11 disc areas | Standard Deviation 1.1 |
| Group B: Ranibizumab 0.5 mg | Mean Change From Baseline in Total Area of Choroidal Neovascularization of the Study Eye in Group B | Mean change from Baseline at Month 12 [N=34, 40] | 0.23 disc areas | Standard Deviation 1.08 |
| Group B: Ranibizumab 0.5 mg | Mean Change From Baseline in Total Area of Choroidal Neovascularization of the Study Eye in Group B | Baseline [N=35, 41] | 2.03 disc areas | Standard Deviation 1.66 |
| Group B: Ranibizumab 0.5 mg | Mean Change From Baseline in Total Area of Choroidal Neovascularization of the Study Eye in Group B | Mean change from Baseline at Month 3 [N=34, 40] | 0.13 disc areas | Standard Deviation 0.75 |
| Group B: Ranibizumab 0.5 mg | Mean Change From Baseline in Total Area of Choroidal Neovascularization of the Study Eye in Group B | Mean change from Baseline at Month 6 [N=34, 40] | 0.04 disc areas | Standard Deviation 0.76 |
| Group B: Ranibizumab 0.5 mg | Mean Change From Baseline in Total Area of Choroidal Neovascularization of the Study Eye in Group B | Mean change from Baseline at Month 9 [N=34, 40] | 0.21 disc areas | Standard Deviation 0.9 |
Secondary
Mean Change From Baseline in Total Area of Leakage From CNV Plus Staining of Retinal Pigment Epithelium of the Study Eye in Group B
Area of leakage from CNV plus staining of retinal pigment epithelium was assessed by fluorescein angiography in conjunction with color fundus photography. Analysis was performed by the central reading center. The total area is expressed as Macular Photocoagulation Study standard Disc Areas (DA; equivalent to 2.54 mm\^2 on the retina).
Time frame: Baseline, Months 3, 6, 9 and 12
Population: Intent-to treat (ITT) population for Group B patients consisted of all patients randomized in Group B that received at least one dose of study drug and had at least one post-baseline assessment. The Last Observation Carried Forward (LOCF) was used to impute missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group B: Ranibizumab 0.3 mg | Mean Change From Baseline in Total Area of Leakage From CNV Plus Staining of Retinal Pigment Epithelium of the Study Eye in Group B | Mean change from Baseline at Month 3 [N=34, 40] | -0.76 disc areas | Standard Deviation 0.85 |
| Group B: Ranibizumab 0.3 mg | Mean Change From Baseline in Total Area of Leakage From CNV Plus Staining of Retinal Pigment Epithelium of the Study Eye in Group B | Mean change from Baseline at Month 9 [N=34, 40] | -1.39 disc areas | Standard Deviation 1.02 |
| Group B: Ranibizumab 0.3 mg | Mean Change From Baseline in Total Area of Leakage From CNV Plus Staining of Retinal Pigment Epithelium of the Study Eye in Group B | Mean change from Baseline at Month 6 [N=34, 40] | -1.21 disc areas | Standard Deviation 0.87 |
| Group B: Ranibizumab 0.3 mg | Mean Change From Baseline in Total Area of Leakage From CNV Plus Staining of Retinal Pigment Epithelium of the Study Eye in Group B | Mean change from Baseline at Month 12 [N=34, 40] | -1.50 disc areas | Standard Deviation 1.08 |
| Group B: Ranibizumab 0.3 mg | Mean Change From Baseline in Total Area of Leakage From CNV Plus Staining of Retinal Pigment Epithelium of the Study Eye in Group B | Baseline [N=35, 41] | 2.31 disc areas | Standard Deviation 1.17 |
| Group B: Ranibizumab 0.5 mg | Mean Change From Baseline in Total Area of Leakage From CNV Plus Staining of Retinal Pigment Epithelium of the Study Eye in Group B | Mean change from Baseline at Month 12 [N=34, 40] | -1.39 disc areas | Standard Deviation 1.48 |
| Group B: Ranibizumab 0.5 mg | Mean Change From Baseline in Total Area of Leakage From CNV Plus Staining of Retinal Pigment Epithelium of the Study Eye in Group B | Baseline [N=35, 41] | 2.49 disc areas | Standard Deviation 1.54 |
| Group B: Ranibizumab 0.5 mg | Mean Change From Baseline in Total Area of Leakage From CNV Plus Staining of Retinal Pigment Epithelium of the Study Eye in Group B | Mean change from Baseline at Month 3 [N=34, 40] | -0.74 disc areas | Standard Deviation 1.21 |
| Group B: Ranibizumab 0.5 mg | Mean Change From Baseline in Total Area of Leakage From CNV Plus Staining of Retinal Pigment Epithelium of the Study Eye in Group B | Mean change from Baseline at Month 6 [N=34, 40] | -1.10 disc areas | Standard Deviation 1.19 |
| Group B: Ranibizumab 0.5 mg | Mean Change From Baseline in Total Area of Leakage From CNV Plus Staining of Retinal Pigment Epithelium of the Study Eye in Group B | Mean change from Baseline at Month 9 [N=34, 40] | -1.26 disc areas | Standard Deviation 1.45 |
Secondary
Mean Change From Baseline in Total Retinal Volume of the Study Eye in Group B
Total retinal volume was assessed by Optical Coherence tomography (OCT) at a subset of the study sites and was analyzed by the central reading center.
Time frame: Baseline, Months 3, 6, 9 and 12
Population: OCT was performed in a total of 58 patients at selected sites. Group B Intent-to treat (ITT) population, observed data only are included. The assessed sample size was small for total retinal volume data because the central reading center judged Can not grade due to retinal pigment epithelium disruption associated with CNV secondary to AMD.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group B: Ranibizumab 0.3 mg | Mean Change From Baseline in Total Retinal Volume of the Study Eye in Group B | Mean change from Baseline at Month 3 [N=7, 7] | -0.78 micrometers | Standard Deviation 0.74 |
| Group B: Ranibizumab 0.3 mg | Mean Change From Baseline in Total Retinal Volume of the Study Eye in Group B | Mean change from Baseline at Month 9 [N=4, 5] | -0.48 micrometers | Standard Deviation 0.03 |
| Group B: Ranibizumab 0.3 mg | Mean Change From Baseline in Total Retinal Volume of the Study Eye in Group B | Baseline [N=11, 11] | 7.23 micrometers | Standard Deviation 0.84 |
| Group B: Ranibizumab 0.3 mg | Mean Change From Baseline in Total Retinal Volume of the Study Eye in Group B | Mean change from Baseline at Month 12 [N=6, 6] | -0.95 micrometers | Standard Deviation 1.14 |
| Group B: Ranibizumab 0.3 mg | Mean Change From Baseline in Total Retinal Volume of the Study Eye in Group B | Mean change from Baseline at Month 6 [N=6, 6] | -0.52 micrometers | Standard Deviation 0.6 |
| Group B: Ranibizumab 0.5 mg | Mean Change From Baseline in Total Retinal Volume of the Study Eye in Group B | Mean change from Baseline at Month 12 [N=6, 6] | -0.42 micrometers | Standard Deviation 0.67 |
| Group B: Ranibizumab 0.5 mg | Mean Change From Baseline in Total Retinal Volume of the Study Eye in Group B | Baseline [N=11, 11] | 7.36 micrometers | Standard Deviation 0.97 |
| Group B: Ranibizumab 0.5 mg | Mean Change From Baseline in Total Retinal Volume of the Study Eye in Group B | Mean change from Baseline at Month 3 [N=7, 7] | -0.67 micrometers | Standard Deviation 0.71 |
| Group B: Ranibizumab 0.5 mg | Mean Change From Baseline in Total Retinal Volume of the Study Eye in Group B | Mean change from Baseline at Month 6 [N=6, 6] | -0.92 micrometers | Standard Deviation 0.96 |
| Group B: Ranibizumab 0.5 mg | Mean Change From Baseline in Total Retinal Volume of the Study Eye in Group B | Mean change from Baseline at Month 9 [N=4, 5] | -0.28 micrometers | Standard Deviation 0.83 |
Secondary
Percentage of Participants in Group B With Absence of Leakage in the Study Eye at Month 3, 6, 9 and 12.
Area of leakage was assessed by fluorescein angiography in conjunction with color fundus photography. Analysis was performed at the central reading center.
Time frame: Months 3, 6, 9 and 12
Population: Intent-to treat (ITT) population for Group B patients consisted of all patients randomized in Group B that received at least one dose of study drug and for whom data was available. The Last Observation Carried Forward (LOCF) was used to impute missing data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group B: Ranibizumab 0.3 mg | Percentage of Participants in Group B With Absence of Leakage in the Study Eye at Month 3, 6, 9 and 12. | Month 3 | 2.9 Percentage of participants |
| Group B: Ranibizumab 0.3 mg | Percentage of Participants in Group B With Absence of Leakage in the Study Eye at Month 3, 6, 9 and 12. | Month 9 | 26.5 Percentage of participants |
| Group B: Ranibizumab 0.3 mg | Percentage of Participants in Group B With Absence of Leakage in the Study Eye at Month 3, 6, 9 and 12. | Month 12 | 35.3 Percentage of participants |
| Group B: Ranibizumab 0.3 mg | Percentage of Participants in Group B With Absence of Leakage in the Study Eye at Month 3, 6, 9 and 12. | Month 6 | 8.8 Percentage of participants |
| Group B: Ranibizumab 0.5 mg | Percentage of Participants in Group B With Absence of Leakage in the Study Eye at Month 3, 6, 9 and 12. | Month 12 | 35.0 Percentage of participants |
| Group B: Ranibizumab 0.5 mg | Percentage of Participants in Group B With Absence of Leakage in the Study Eye at Month 3, 6, 9 and 12. | Month 3 | 7.5 Percentage of participants |
| Group B: Ranibizumab 0.5 mg | Percentage of Participants in Group B With Absence of Leakage in the Study Eye at Month 3, 6, 9 and 12. | Month 6 | 15.0 Percentage of participants |
| Group B: Ranibizumab 0.5 mg | Percentage of Participants in Group B With Absence of Leakage in the Study Eye at Month 3, 6, 9 and 12. | Month 9 | 25.0 Percentage of participants |