Macular Edema Secondary to Branch Retinal Vein Occlusion (BRVO)
Conditions
Keywords
Ranibizumab, Grid&Direct short pulse laser photocoagulation, Macular edema, Branch retinal vein occlusion, BRVO, BCVA, CSFT, pro re nata
Brief summary
This is a Phase IV, randomized, open-label, active-controlled, 2-arm, multicenter study. The primary objective was assessed by the difference in the mean number of ranibizumab injections applied up to Month 11 between the 2 treatment arms. Patients were randomized in a 1:1 ratio to 1 of the 2 treatment arms; i.e. Arm 1 ranibizumab monotherapy, Arm 2 ranibizumab with Grid&Direct short pulse laser photocoagulation combination therapy. There were 3 periods in this study: Screening Period (visit 1), Treatment Period (visit 2 to Visit 13) and Follow-up Period (visit 14). In addition to screening and Baseline (visit 2), there were monthly visits from Month 1 to Month 12. This study included male and female patients (≥20 years old) diagnosed with visual impairment due to ME secondary to BRVO.
Interventions
BIOLOGICALRanibizumab
Ranibizumab is a biologic and known anti-VEGF (vascular endothelial growth factor) medication approved for treatment of ME (Macular Edema) due to RVO (Retinal Vein occlusion) 0.5 mg ranibizumab applied one + PRN as intravitreal injection of 0.05 mL, with or without laser treatment
RADIATIONGrid&Direct short pulse laser photocoagulation
Grid&Direct short pulse laser photocoagulation is a kind of laser treatment to retina within vascular arcades and used to suppress macular edema
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase IV, randomized, open-label, active-controlled, 2-arm, multicenter study
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of visual impairment exclusively due to ME secondary to BRVO * Best-corrected visual acuity score at Screening and Baseline (Day 1) between 0.5 and 0.05 decimal (i.e., between 73 and 19 letters in Early Treatment Diabetic Retinopathy Study (ETDRS) testing) with Landolt C charts inclusively (i.e., approximate logarithm of the minimum angle of resolution (logMAR) units of 0.3 to 1.30). * At Baseline (Day1), a maximum BCVA gain of 0.2 units logMAR conversion inclusively from screening is allowed as long as the BCVA score does not exceed the upper limit of 0.3 units logMAR. * Increased central subfoveal thickness (\> 300 µm at Baseline (Day 1) when measured by SD-OCT) * Duration of vision deterioration ≤6 months (determined by self-report) at screening
Exclusion criteria
* Pregnant or nursing (lactating) women * Stroke or myocardial infarction less than 3 months before Screening * Uncontrolled blood pressure defined as systolic value of \>160 mm Hg or diastolic value of \>100 mm Hg at Screening or Baseline (Day 1) Antihypertensive treatment can be initiated and must be taken for at least 30 days after which the patient can be assessed for study eligibility a second time * Any active periocular or ocular infection or inflammation (e.g., blepharitis, conjunctivitis, keratitis, scleritis, uveitis, endophthalmitis) at the time of Screening or Baseline (Day 1) in either eye * Uncontrolled glaucoma (intraocular pressure (IOP) ≥30 mm Hg on medication or according to investigator's judgment) at the time of Screening or Baseline (Day 1) or diagnosed within 6 months before Baseline (Day 1) in either eye * Neovascularization of the iris or neovascular glaucoma in the study eye * Use of any systemic anti-VEGF drugs within 6 months before Baseline (Day1) (e.g., sorafenib (Nexavar®), sunitinib (Sutent®), bevacizumab (Avastin®), ziv-aflibercept (ZALTRAP®)) * Treatment (or anticipated treatment in the fellow eye for non-RVO indications during the study) with any anti-angiogenic drugs (including any anti-VEGF agents) within 3 months before Baseline (Day1) in fellow eye or before Baseline (Day 1) in the study eye (e.g., pegaptanib (Macugen®), ranibizumab (Lucentis®), bevacizumab (Avastin®), and aflibercept (EYLEA®)) * Panretinal laser photocoagulation within 1 month before Baseline (Day1) or anticipated or scheduled within the next 12 months (Study periods) following Baseline (Day1) in the study eye * Any giving of focal or grid laser photocoagulation before Baseline (Day1) in the study eye * Use of intra- or periocular corticosteroids (including sub-Tenon) within 3 months before Screening in the study eye. * Any use of intraocular corticosteroid implants (e.g., dexamethasone (Ozurdex®), fluocinolone acetonide (Iluvien®)) in the study eye
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Mean Number of Ranibizumab Injections | Month 1 through Month 12 | Number of ranibizumab treatments from Day 1 to Month 11 using full analysis set (observed) based on a stratified Cochran-Mantel-Haenszel (CMH) test. Stratification was done based on categories of baseline decimal VA (\<0.3, or =\>0.3). Difference of mean number of injections, 95% confidence interval (CI) of difference and one-sided p-value of the CMH test was reported. Analysis was conducted within the FAS with observed data. Stratification was based on baseline visual acuity on logMAR scale (\<0.52, \>=0.52). Test was one-sided. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Mean Change in Best Corrected Visual Acuity (BCVA) Using Decimal Chart and Early Treatment Diabetic Retinopathy Study (ETDRS) Compared to Baseline | Month 1 through Month 12 (for ETDRS: Month 6 and Month 12) | Summary of BCVA (letters) absolute value and change from Baseline at Month 12 in the study eye - full analysis set (LOCF) was based on an analysis of variance (ANOVA) model with treatment group, and stratification factors. Stratification was done based on categories of baseline decimal VA (\<0.3, or =\>0.3). The analyses was conducted within the FAS using the LOCF approach Stratification was based on baseline visual acuity on logMAR scale (\<0.52, \>=0.52). Test was one-sided. |
| The Mean Change in BCVA From Month 1 Through Month 12 Compared to Baseline (Day 1) by the Treatment Arms | Month 1 through Month 12 | Summary of BCVA (logMAR) absolute value and change from Baseline at Month 12 in the study eye - full analysis set (LOCF) was based on an analysis of variance (ANOVA) model with treatment group, and stratification factors. Stratification was based on baseline visual acuity (\< 0.52, \>= 0.52). The analyses was conducted within the FAS using the LOCF approach |
| BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | Month 6 and Month 12 | Endpoints related to the number and proportion of patients with BCVA letter gain or loss from Baseline (Day1) was analyzed via stratified CMH test with stratification factors as described in primary model. The mean (SD) average (per patient) BCVA (logMAR) change from Baseline through Month 12 Summary of BCVA (logMAR) mean average change from Baseline from Month 1 through Month 12 in the study eye |
| The Mean Change in Change in Central Subfield Foveal Thickness (CSFT) From Month 1 Through Month 12 Compared to Baseline (Day1) by the Treatment Arms | Month 1 through Month 12 | The mean change in investigator-assessed CSFT from Month 1 through Month 12 was compared to Baseline (Day1) by the treatment arms. The analyses at each visit was based on an analysis of variance (ANOVA) model as analogous to BCVA. The analyses was conducted within the FAS using the Last-Observation-Carried-Forward (LOCF) approach |
Countries
Japan
Participant flow
Recruitment details
73 patients were screened and 59 were randomized on a 1:1 ratio to the ranibizumab group (29 patients) and ranibizumab with laser group (30 patients). Of the randomized patients, 56 (94.9%) completed the study and 11 months of treatment. 3 (5.1%) discontinued both study and study treatment: 2 (3.4%) withdrew consent and 1 (1.7%) had adverse event
Pre-assignment details
Below is the participant flow of Randomized patients
Participants by arm
| Arm | Count |
|---|---|
| Ranibizumab 0.5 mg 0.5 mg ranibizumab applied one + PRN as intravitreal injection of 0.05 mL | 29 |
| Ranibizumab 0.5 mg and Laser 0.5 mg ranibizumab applied one + PRN as intravitreal injection of 0.05 mL with the laser treatment | 30 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Ranibizumab 0.5 mg | Ranibizumab 0.5 mg and Laser | Total |
|---|---|---|---|
| Age, Continuous | 66.8 years STANDARD_DEVIATION 9.91 | 66.7 years STANDARD_DEVIATION 9.83 | 66.8 years STANDARD_DEVIATION 9.78 |
| Age, Customized <65 years | 12 Participants | 11 Participants | 23 Participants |
| Age, Customized >=65 years | 17 Participants | 19 Participants | 36 Participants |
| Race/Ethnicity, Customized Asian | 29 Participants | 30 Participants | 59 Participants |
| Sex: Female, Male Female | 10 Participants | 19 Participants | 29 Participants |
| Sex: Female, Male Male | 19 Participants | 11 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 30 | 0 / 59 |
| other Total, other adverse events | 16 / 29 | 15 / 30 | 31 / 59 |
| serious Total, serious adverse events | 1 / 29 | 2 / 30 | 3 / 59 |
Outcome results
Primary
Difference in Mean Number of Ranibizumab Injections
Number of ranibizumab treatments from Day 1 to Month 11 using full analysis set (observed) based on a stratified Cochran-Mantel-Haenszel (CMH) test. Stratification was done based on categories of baseline decimal VA (\<0.3, or =\>0.3). Difference of mean number of injections, 95% confidence interval (CI) of difference and one-sided p-value of the CMH test was reported. Analysis was conducted within the FAS with observed data. Stratification was based on baseline visual acuity on logMAR scale (\<0.52, \>=0.52). Test was one-sided.
Time frame: Month 1 through Month 12
Population: Randomized Set, i.e.; all randomized patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ranibizumab 0.5 mg | Difference in Mean Number of Ranibizumab Injections | 4.3 number of injections | Standard Deviation 2.51 |
| Ranibizumab 0.5 mg Laser | Difference in Mean Number of Ranibizumab Injections | 4.1 number of injections | Standard Deviation 2.41 |
p-value: 0.36895% CI: [-1.49, 1.07]Cochran-Mantel-Haenszel
Secondary
BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye
Endpoints related to the number and proportion of patients with BCVA letter gain or loss from Baseline (Day1) was analyzed via stratified CMH test with stratification factors as described in primary model. The mean (SD) average (per patient) BCVA (logMAR) change from Baseline through Month 12 Summary of BCVA (logMAR) mean average change from Baseline from Month 1 through Month 12 in the study eye
Time frame: Month 6 and Month 12
Population: Full Analysis Set (FAS) consisted of all randomized patients who received at least one administration of ranibizumab injection
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ranibizumab 0.5 mg | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | Month 6 - BCVA improvement of >=30 | 4 Participants |
| Ranibizumab 0.5 mg | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | Month 12 - BCVA improvement of >=1 | 27 Participants |
| Ranibizumab 0.5 mg | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | month 6 - BCVA improvement of >=10 | 22 Participants |
| Ranibizumab 0.5 mg | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | Month 12 - BCVA improvement of >=5 | 27 Participants |
| Ranibizumab 0.5 mg | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | month 6 Score >=73 | 12 Participants |
| Ranibizumab 0.5 mg | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | Month 12 - BCVA improvement of >=10 | 24 Participants |
| Ranibizumab 0.5 mg | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | month 6 - BCVA improvement of >=5 | 26 Participants |
| Ranibizumab 0.5 mg | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | Month 12 - BCVA improvement of >=15 | 21 Participants |
| Ranibizumab 0.5 mg | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | month 6 Score >=80 | 8 Participants |
| Ranibizumab 0.5 mg | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | Month 12 - BCVA improvement of >=30 | 9 Participants |
| Ranibizumab 0.5 mg | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | Month 6 - BCVA improvement of >=15 | 17 Participants |
| Ranibizumab 0.5 mg | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | month 12 Score >=73 | 20 Participants |
| Ranibizumab 0.5 mg | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | month 6 Score >=85 | 3 Participants |
| Ranibizumab 0.5 mg | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | month 12 Score >=80 | 8 Participants |
| Ranibizumab 0.5 mg | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | Month 6 - BCVA improvement of >=1 | 27 Participants |
| Ranibizumab 0.5 mg | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | month 6 loss of <15 | 28 Participants |
| Ranibizumab 0.5 mg | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | month 12 Loss of <15 | 29 Participants |
| Ranibizumab 0.5 mg | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | month 12 Score >=85 | 4 Participants |
| Ranibizumab 0.5 mg Laser | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | month 12 Loss of <15 | 29 Participants |
| Ranibizumab 0.5 mg Laser | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | Month 6 - BCVA improvement of >=1 | 24 Participants |
| Ranibizumab 0.5 mg Laser | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | month 6 - BCVA improvement of >=5 | 21 Participants |
| Ranibizumab 0.5 mg Laser | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | month 6 - BCVA improvement of >=10 | 16 Participants |
| Ranibizumab 0.5 mg Laser | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | Month 6 - BCVA improvement of >=15 | 12 Participants |
| Ranibizumab 0.5 mg Laser | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | Month 6 - BCVA improvement of >=30 | 1 Participants |
| Ranibizumab 0.5 mg Laser | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | month 6 Score >=73 | 10 Participants |
| Ranibizumab 0.5 mg Laser | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | month 6 Score >=80 | 2 Participants |
| Ranibizumab 0.5 mg Laser | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | month 6 Score >=85 | 1 Participants |
| Ranibizumab 0.5 mg Laser | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | month 6 loss of <15 | 29 Participants |
| Ranibizumab 0.5 mg Laser | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | Month 12 - BCVA improvement of >=1 | 28 Participants |
| Ranibizumab 0.5 mg Laser | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | Month 12 - BCVA improvement of >=5 | 25 Participants |
| Ranibizumab 0.5 mg Laser | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | Month 12 - BCVA improvement of >=10 | 18 Participants |
| Ranibizumab 0.5 mg Laser | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | Month 12 - BCVA improvement of >=15 | 15 Participants |
| Ranibizumab 0.5 mg Laser | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | Month 12 - BCVA improvement of >=30 | 3 Participants |
| Ranibizumab 0.5 mg Laser | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | month 12 Score >=73 | 10 Participants |
| Ranibizumab 0.5 mg Laser | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | month 12 Score >=80 | 13 Participants |
| Ranibizumab 0.5 mg Laser | BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye | month 12 Score >=85 | 0 Participants |
Secondary
The Mean Change in BCVA From Month 1 Through Month 12 Compared to Baseline (Day 1) by the Treatment Arms
Summary of BCVA (logMAR) absolute value and change from Baseline at Month 12 in the study eye - full analysis set (LOCF) was based on an analysis of variance (ANOVA) model with treatment group, and stratification factors. Stratification was based on baseline visual acuity (\< 0.52, \>= 0.52). The analyses was conducted within the FAS using the LOCF approach
Time frame: Month 1 through Month 12
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ranibizumab 0.5 mg | The Mean Change in BCVA From Month 1 Through Month 12 Compared to Baseline (Day 1) by the Treatment Arms | change from baseline to month 12 | -0.478 logMAR | Standard Deviation 0.2586 |
| Ranibizumab 0.5 mg | The Mean Change in BCVA From Month 1 Through Month 12 Compared to Baseline (Day 1) by the Treatment Arms | baseline | 0.553 logMAR | Standard Deviation 0.2276 |
| Ranibizumab 0.5 mg | The Mean Change in BCVA From Month 1 Through Month 12 Compared to Baseline (Day 1) by the Treatment Arms | month12 | 0.075 logMAR | Standard Deviation 0.1909 |
| Ranibizumab 0.5 mg Laser | The Mean Change in BCVA From Month 1 Through Month 12 Compared to Baseline (Day 1) by the Treatment Arms | month12 | 0.143 logMAR | Standard Deviation 0.1682 |
| Ranibizumab 0.5 mg Laser | The Mean Change in BCVA From Month 1 Through Month 12 Compared to Baseline (Day 1) by the Treatment Arms | baseline | 0.558 logMAR | Standard Deviation 0.1719 |
| Ranibizumab 0.5 mg Laser | The Mean Change in BCVA From Month 1 Through Month 12 Compared to Baseline (Day 1) by the Treatment Arms | change from baseline to month 12 | -0.413 logMAR | Standard Deviation 0.1969 |
p-value: 0.270795% CI: [-0.045, 0.158]ANOVA
Secondary
The Mean Change in Best Corrected Visual Acuity (BCVA) Using Decimal Chart and Early Treatment Diabetic Retinopathy Study (ETDRS) Compared to Baseline
Summary of BCVA (letters) absolute value and change from Baseline at Month 12 in the study eye - full analysis set (LOCF) was based on an analysis of variance (ANOVA) model with treatment group, and stratification factors. Stratification was done based on categories of baseline decimal VA (\<0.3, or =\>0.3). The analyses was conducted within the FAS using the LOCF approach Stratification was based on baseline visual acuity on logMAR scale (\<0.52, \>=0.52). Test was one-sided.
Time frame: Month 1 through Month 12 (for ETDRS: Month 6 and Month 12)
Population: The Full Analysis Set (FAS) consisted of all randomized patients who received at least one administration of ranibizumab injection.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ranibizumab 0.5 mg | The Mean Change in Best Corrected Visual Acuity (BCVA) Using Decimal Chart and Early Treatment Diabetic Retinopathy Study (ETDRS) Compared to Baseline | baseline | 52.86 letters read correctly | Standard Deviation 13.384 |
| Ranibizumab 0.5 mg | The Mean Change in Best Corrected Visual Acuity (BCVA) Using Decimal Chart and Early Treatment Diabetic Retinopathy Study (ETDRS) Compared to Baseline | month 12 | 74.83 letters read correctly | Standard Deviation 9.74 |
| Ranibizumab 0.5 mg | The Mean Change in Best Corrected Visual Acuity (BCVA) Using Decimal Chart and Early Treatment Diabetic Retinopathy Study (ETDRS) Compared to Baseline | change from baseline to month 12 | 21.97 letters read correctly | Standard Deviation 14.749 |
| Ranibizumab 0.5 mg Laser | The Mean Change in Best Corrected Visual Acuity (BCVA) Using Decimal Chart and Early Treatment Diabetic Retinopathy Study (ETDRS) Compared to Baseline | baseline | 54.03 letters read correctly | Standard Deviation 9.828 |
| Ranibizumab 0.5 mg Laser | The Mean Change in Best Corrected Visual Acuity (BCVA) Using Decimal Chart and Early Treatment Diabetic Retinopathy Study (ETDRS) Compared to Baseline | month 12 | 69.59 letters read correctly | Standard Deviation 8.842 |
| Ranibizumab 0.5 mg Laser | The Mean Change in Best Corrected Visual Acuity (BCVA) Using Decimal Chart and Early Treatment Diabetic Retinopathy Study (ETDRS) Compared to Baseline | change from baseline to month 12 | 15.00 letters read correctly | Standard Deviation 10.296 |
p-value: 0.034995% CI: [-12.67, -0.48]ANOVA
Secondary
The Mean Change in Change in Central Subfield Foveal Thickness (CSFT) From Month 1 Through Month 12 Compared to Baseline (Day1) by the Treatment Arms
The mean change in investigator-assessed CSFT from Month 1 through Month 12 was compared to Baseline (Day1) by the treatment arms. The analyses at each visit was based on an analysis of variance (ANOVA) model as analogous to BCVA. The analyses was conducted within the FAS using the Last-Observation-Carried-Forward (LOCF) approach
Time frame: Month 1 through Month 12
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ranibizumab 0.5 mg | The Mean Change in Change in Central Subfield Foveal Thickness (CSFT) From Month 1 Through Month 12 Compared to Baseline (Day1) by the Treatment Arms | baseline | 563.3 mm | Standard Deviation 146.92 |
| Ranibizumab 0.5 mg | The Mean Change in Change in Central Subfield Foveal Thickness (CSFT) From Month 1 Through Month 12 Compared to Baseline (Day1) by the Treatment Arms | month 12 | 257.0 mm | Standard Deviation 43.44 |
| Ranibizumab 0.5 mg | The Mean Change in Change in Central Subfield Foveal Thickness (CSFT) From Month 1 Through Month 12 Compared to Baseline (Day1) by the Treatment Arms | change in baseline from month 12 | -306.3 mm | Standard Deviation 164.35 |
| Ranibizumab 0.5 mg Laser | The Mean Change in Change in Central Subfield Foveal Thickness (CSFT) From Month 1 Through Month 12 Compared to Baseline (Day1) by the Treatment Arms | baseline | 553.3 mm | Standard Deviation 182.39 |
| Ranibizumab 0.5 mg Laser | The Mean Change in Change in Central Subfield Foveal Thickness (CSFT) From Month 1 Through Month 12 Compared to Baseline (Day1) by the Treatment Arms | month 12 | 285.1 mm | Standard Deviation 82.8 |
| Ranibizumab 0.5 mg Laser | The Mean Change in Change in Central Subfield Foveal Thickness (CSFT) From Month 1 Through Month 12 Compared to Baseline (Day1) by the Treatment Arms | change in baseline from month 12 | -261.3 mm | Standard Deviation 180.23 |
p-value: 0.760295% CI: [-62.65, 85.28]ANOVA