Diabetic Macular Edema
Conditions
Keywords
DME, Diabetic macula edema, RETAIN, ranibizumab
Brief summary
The purpose of this study is to demonstrate that two investigational treatment regimens have the potential to result in a superior visual acuity improvement as compared to a ranibizumab pro re nata (PRN=as needed) treatment regimen.
Interventions
DRUGRanibizumab
Ranibizumab (Lucentis®) was supplied in vials containing a dose of 0.5 mg/0.05 mL in an aqueous solution (pH 5.5) with histidine, trehalose, and polysorbate 20.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patient * Patients with Type 1 or Type 2 diabetes mellitus (according to American Diabetes Association or World Health Organization \[WHO\] guidelines) with glycosylated hemoglobin (HbA1c) ≤ 12.0% at screening (Visit 1). Patients should be on diet, exercise, and/or pharmacological treatment for diabetes. Treatment for diabetes must have been stable for at least 3 month. Ocular * Patients with visual impairment due to DME in at least one eye who are eligible for laser treatment in the opinion of the investigator. If both eyes are eligible, the one with the worse visual acuity, as assessed at Visit 1, will be selected by the investigator as the study eye. * BCVA ≥ 39 and ≤78 letters in the study eye and, inclusively, using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters (approximate Snellen equivalent of 20/32 to 20/160) at screening. * Concomitant conditions in the study eye are only permitted if, in the opinion of the investigator, they do not prevent improvement of visual acuity on study treatment.
Exclusion criteria
Patient Compliance/ Administrative * Pregnant or nursing (lactating) women. Ocular medical history * Active intraocular inflammation (grade trace or above) in either eye at enrollment. * Any active infection (e.g. conjunctivitis, keratitis, scleritis, uveitis, endophthalmitis) in either eye at the time of enrollment. * History of uveitis in either eye at any time. * Structural damage within 0.5 disc diameter of the center of the macular in the study eye likely to preclude improvement in visual acuity following the resolution of macular edema. * Uncontrolled glaucoma in either eye at screening. Prior Ocular treatments * Panretinal laser photocoagulation in the study eye within 6 months prior to randomization. * Focal/grid laser photocoagulation in the study eye within 3 months prior to randomization. * Treatment with anti-angiogenic drugs in either eye. Systemic conditions or treatments * History of stroke within 6 months prior to enrollment. * Renal failure requiring dialysis. * Untreated diabetes mellitus. * Blood pressure systolic \> 160 mmHg or diastolic \> 100 mmHg. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 12 | Baseline to Month 12 | Visual acuity was assessed at every study visit for the study eye using best correction determined from protocol refraction. The BCVA measurements were taken in a sitting position using ETDRS-like VA testing charts at a starting distance of 4 meters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Visual Acuity of the Study Eye: Change From Baseline at Month 12 | Baseline and Month 12 | Visual acuity was assessed at every study visit for the study eye using best correction determined from protocol refraction. The BCVA measurements were taken in a sitting position using ETDRS-like VA testing charts at a starting distance of 4 meters. |
| Visual Acuity of the Study Eye: Change From Baseline at Month 24 | Baseline and Month 24 | Visual acuity was assessed at every study visit for the study eye using best correction determined from protocol refraction. The BCVA measurements were taken in a sitting position using ETDRS-like VA testing charts at a starting distance of 4 meters. |
| Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 12 | Baseline, Month 12 | Visual acuity was assessed at every study visit for the study eye using best correction determined from protocol refraction. The BCVA measurements were taken in a sitting position using ETDRS-like VA testing charts at a starting distance of 4 meters. |
| Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 24 | Baseline, 24 month | Visual acuity was assessed at every study visit for the study eye using best correction determined from protocol refraction. The BCVA measurements were taken in a sitting position using ETDRS-like VA testing charts at a starting distance of 4 meters. |
| Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 24 | Baseline to Month 24 | Visual acuity was assessed at every study visit for the study eye using best correction determined from protocol refraction. The BCVA measurements were taken in a sitting position using ETDRS-like VA testing charts at a starting distance of 4 meters. |
| Central Subfield Thickness of the Study Eye: Percent Change From Baseline at Month 24 | Baseline and 24 month | High Resolution OCT was performed at every study visit by Spectral Domain OCT (if not available Time Domain OCT was acceptable) and the images were transferred to a digital video disc. These assessments were performed by trained and adequately qualified experts at the sites and prior to any study drug administration. CSFT is the average retinal thickness of the circular area with 1 mm diameter around the foveal center. |
| Visual Functioning Questionnaire (VFQ-25) Change From Baseline in Total Score at Month 12 and Month 24 | Baseline, Month 12 and Month 24 | The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) was used to measure the influence of visual disability and symptoms on general health. The 12 subscales in the VFQ-25 are general health, general vision, ocular pain, near activities, distance activities, social function, mental health, role difficulties, dependency, driving, color vision, and peripheral vision. For each, the patient was asked to rate their condition on a scale of 1-5 or 1-6, where a low number reflects a better outcome. Each response was recoded per the scoring rules outlined in the National Eye Institute (NEI) VFQ-25 Scoring Algorithm. Under this scoring algorithm , the recoded values range between 0 and 100 and a high score means a better functioning |
| EuroQoL (EQ-5D) Thermometer Score: Change From Baseline at Month 12 and Month 24 | Baseline, Month 12 and Month 24 | The Euro Quality of Life Questionnaire (EQ-5D) is an indirect utility questionnaire. It is a standardized instrument was utilized to measure health outcomes related to 5 dimensions, namely: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The possible range for each dimension was 1 to 3, where 1= no problems, 2=some problems and 3=extreme problems . A composite health index was then defined by combining the levels for each dimension. Overall, 243 health states are possible. For each health state, the EuroQol group has assigned a utility value typically between 0 and 1 with lower scores representing a higher level of dysfunction |
| Central Subfield Thickness of the Study Eye: Percent Change From Baseline at Month 12 | Baseline, Month 12 | High Resolution OCT was performed at every study visit by Spectral Domain OCT (if not available Time Domain OCT was acceptable) and the images were transferred to a digital video disc. These assessments were performed by trained and adequately qualified experts at the sites and prior to any study drug administration. CSFT is the average retinal thickness of the circular area with 1 mm diameter around the foveal center. |
Countries
Belgium, Czechia, France, Greece, Hungary, Ireland, Italy, Netherlands, Poland, Portugal, Spain, Switzerland, United Kingdom
Participant flow
Recruitment details
A total of 373 patients with macular edema and visual impairment secondary to DME were enrolled. A total of 372 patients were randomized. One patient was excluded from all analyses due to administrative problems
Pre-assignment details
Antimicrobial eye drops were dispensed at each study visit (PRN ranibizumab) or at visits with scheduled injections (TE ranibizumab + laser or TE ranibizumab alone).
Participants by arm
| Arm | Count |
|---|---|
| TE Ranibizumad 0.5 mg and Laser Patients received an injection ranibizumab and laser therapy. | 121 |
| TE Ranibizumab 0.5 mg Alone Patients received an intravitreal injection ranibizumab | 128 |
| PRN Ranibizumab 0.5 mg Participants received ranibizumab intravitreal injection therapy as needed according to signs and symptoms of disease. | 123 |
| Total | 372 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Abnormal test result | 1 | 0 | 0 |
| Overall Study | Adverse Event | 6 | 2 | 5 |
| Overall Study | Death | 2 | 4 | 1 |
| Overall Study | Lost to Follow-up | 4 | 0 | 2 |
| Overall Study | Protocol Violation | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 5 | 6 |
Baseline characteristics
| Characteristic | TE Ranibizumad 0.5 mg and Laser | TE Ranibizumab 0.5 mg Alone | PRN Ranibizumab 0.5 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 63.7 Years STANDARD_DEVIATION 9.07 | 63.0 Years STANDARD_DEVIATION 9.83 | 64.5 Years STANDARD_DEVIATION 9.66 | 63.7 Years STANDARD_DEVIATION 9.53 |
| Sex: Female, Male Female | 43 Participants | 51 Participants | 46 Participants | 140 Participants |
| Sex: Female, Male Male | 78 Participants | 77 Participants | 77 Participants | 232 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 98 / 126 | 101 / 126 | 78 / 118 |
| serious Total, serious adverse events | 34 / 126 | 29 / 126 | 26 / 118 |
Outcome results
Primary
Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 12
Visual acuity was assessed at every study visit for the study eye using best correction determined from protocol refraction. The BCVA measurements were taken in a sitting position using ETDRS-like VA testing charts at a starting distance of 4 meters.
Time frame: Baseline to Month 12
Population: Analyzed set included all randomized patients who received at least one application of study treatment and had at least one post baseline efficacy assessment. If missing values occurred without a subsequent observed value, the last observed value was carried forward to subsequent scheduled visits by means of a last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TE Ranibizumad 0.5 mg and Laser | Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 12 | Average Change from Baseline | 5.91 Letters | Standard Deviation 5.532 |
| TE Ranibizumad 0.5 mg and Laser | Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 12 | Average Month 1 to Month 12 | 68.25 Letters | Standard Deviation 11.057 |
| TE Ranibizumad 0.5 mg and Laser | Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 12 | Baseline | 62.3 Letters | Standard Deviation 11.5 |
| TE Ranibizumab 0.5 mg Alone | Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 12 | Average Change from Baseline | 6.14 Letters | Standard Deviation 5.717 |
| TE Ranibizumab 0.5 mg Alone | Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 12 | Baseline | 64.1 Letters | Standard Deviation 10.52 |
| TE Ranibizumab 0.5 mg Alone | Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 12 | Average Month 1 to Month 12 | 70.28 Letters | Standard Deviation 10.284 |
| PRN Ranibizumab 0.5 mg | Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 12 | Average Change from Baseline | 6.20 Letters | Standard Deviation 6.005 |
| PRN Ranibizumab 0.5 mg | Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 12 | Average Month 1 to Month 12 | 71.32 Letters | Standard Deviation 9.984 |
| PRN Ranibizumab 0.5 mg | Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 12 | Baseline | 65.1 Letters | Standard Deviation 10.08 |
Secondary
Central Subfield Thickness of the Study Eye: Percent Change From Baseline at Month 12
High Resolution OCT was performed at every study visit by Spectral Domain OCT (if not available Time Domain OCT was acceptable) and the images were transferred to a digital video disc. These assessments were performed by trained and adequately qualified experts at the sites and prior to any study drug administration. CSFT is the average retinal thickness of the circular area with 1 mm diameter around the foveal center.
Time frame: Baseline, Month 12
Population: Analyzed set included all randomized patients who received at least one application of study treatment and had at least one post baseline efficacy assessment. If missing values occurred without a subsequent observed value, the last observed value was carried forward to subsequent scheduled visits by means of a last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TE Ranibizumad 0.5 mg and Laser | Central Subfield Thickness of the Study Eye: Percent Change From Baseline at Month 12 | -27.09 Percent Change | Standard Deviation 22.992 |
| TE Ranibizumab 0.5 mg Alone | Central Subfield Thickness of the Study Eye: Percent Change From Baseline at Month 12 | -24.35 Percent Change | Standard Deviation 22.027 |
| PRN Ranibizumab 0.5 mg | Central Subfield Thickness of the Study Eye: Percent Change From Baseline at Month 12 | -23.16 Percent Change | Standard Deviation 22.362 |
Secondary
Central Subfield Thickness of the Study Eye: Percent Change From Baseline at Month 24
High Resolution OCT was performed at every study visit by Spectral Domain OCT (if not available Time Domain OCT was acceptable) and the images were transferred to a digital video disc. These assessments were performed by trained and adequately qualified experts at the sites and prior to any study drug administration. CSFT is the average retinal thickness of the circular area with 1 mm diameter around the foveal center.
Time frame: Baseline and 24 month
Population: Analyzed set included all randomized patients who received at least one application of study treatment and had at least one post baseline efficacy assessment. If missing values occurred without a subsequent observed value, the last observed value was carried forward to subsequent scheduled visits by means of a last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TE Ranibizumad 0.5 mg and Laser | Central Subfield Thickness of the Study Eye: Percent Change From Baseline at Month 24 | -32.03 Percent Change | Standard Deviation 25.628 |
| TE Ranibizumab 0.5 mg Alone | Central Subfield Thickness of the Study Eye: Percent Change From Baseline at Month 24 | -24.98 Percent Change | Standard Deviation 26.414 |
| PRN Ranibizumab 0.5 mg | Central Subfield Thickness of the Study Eye: Percent Change From Baseline at Month 24 | -24.97 Percent Change | Standard Deviation 26.678 |
Secondary
EuroQoL (EQ-5D) Thermometer Score: Change From Baseline at Month 12 and Month 24
The Euro Quality of Life Questionnaire (EQ-5D) is an indirect utility questionnaire. It is a standardized instrument was utilized to measure health outcomes related to 5 dimensions, namely: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The possible range for each dimension was 1 to 3, where 1= no problems, 2=some problems and 3=extreme problems . A composite health index was then defined by combining the levels for each dimension. Overall, 243 health states are possible. For each health state, the EuroQol group has assigned a utility value typically between 0 and 1 with lower scores representing a higher level of dysfunction
Time frame: Baseline, Month 12 and Month 24
Population: Analyzed set included all randomized patients who received at least one application of study treatment and had at least one post baseline efficacy assessment. If missing values occurred without a subsequent observed value, the last observed value was carried forward to subsequent scheduled visits by means of a last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TE Ranibizumad 0.5 mg and Laser | EuroQoL (EQ-5D) Thermometer Score: Change From Baseline at Month 12 and Month 24 | Change from Baseline at Month 12 (n=115,123,113) | 0.47 Score on a scale | Standard Deviation 16.487 |
| TE Ranibizumad 0.5 mg and Laser | EuroQoL (EQ-5D) Thermometer Score: Change From Baseline at Month 12 and Month 24 | Baseline | 71.4 Score on a scale | Standard Deviation 17.36 |
| TE Ranibizumad 0.5 mg and Laser | EuroQoL (EQ-5D) Thermometer Score: Change From Baseline at Month 12 and Month 24 | Change from Baseline at Month 24 (n=115,123,113) | 1.35 Score on a scale | Standard Deviation 17.464 |
| TE Ranibizumab 0.5 mg Alone | EuroQoL (EQ-5D) Thermometer Score: Change From Baseline at Month 12 and Month 24 | Change from Baseline at Month 12 (n=115,123,113) | 0.91 Score on a scale | Standard Deviation 13.422 |
| TE Ranibizumab 0.5 mg Alone | EuroQoL (EQ-5D) Thermometer Score: Change From Baseline at Month 12 and Month 24 | Baseline | 70.7 Score on a scale | Standard Deviation 16.1 |
| TE Ranibizumab 0.5 mg Alone | EuroQoL (EQ-5D) Thermometer Score: Change From Baseline at Month 12 and Month 24 | Change from Baseline at Month 24 (n=115,123,113) | 0.11 Score on a scale | Standard Deviation 14.755 |
| PRN Ranibizumab 0.5 mg | EuroQoL (EQ-5D) Thermometer Score: Change From Baseline at Month 12 and Month 24 | Baseline | 72.2 Score on a scale | Standard Deviation 13.24 |
| PRN Ranibizumab 0.5 mg | EuroQoL (EQ-5D) Thermometer Score: Change From Baseline at Month 12 and Month 24 | Change from Baseline at Month 24 (n=115,123,113) | 1.98 Score on a scale | Standard Deviation 14.812 |
| PRN Ranibizumab 0.5 mg | EuroQoL (EQ-5D) Thermometer Score: Change From Baseline at Month 12 and Month 24 | Change from Baseline at Month 12 (n=115,123,113) | 2.52 Score on a scale | Standard Deviation 14.431 |
Secondary
Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 24
Visual acuity was assessed at every study visit for the study eye using best correction determined from protocol refraction. The BCVA measurements were taken in a sitting position using ETDRS-like VA testing charts at a starting distance of 4 meters.
Time frame: Baseline to Month 24
Population: Analyzed set included all randomized patients who received at least one application of study treatment and had at least one post baseline efficacy assessment. If missing values occurred without a subsequent observed value, the last observed value was carried forward to subsequent scheduled visits by means of a last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TE Ranibizumad 0.5 mg and Laser | Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 24 | Average Month 1 to Month 24 | 69.12 Letters | Standard Deviation 11.261 |
| TE Ranibizumad 0.5 mg and Laser | Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 24 | Baseline | 62.3 Letters | Standard Deviation 11.5 |
| TE Ranibizumad 0.5 mg and Laser | Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 24 | Average Change from Baseline | 6.78 Letters | Standard Deviation 5.986 |
| TE Ranibizumab 0.5 mg Alone | Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 24 | Average Month 1 to Month 24 | 70.72 Letters | Standard Deviation 10.924 |
| TE Ranibizumab 0.5 mg Alone | Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 24 | Baseline | 64.1 Letters | Standard Deviation 10.52 |
| TE Ranibizumab 0.5 mg Alone | Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 24 | Average Change from Baseline | 6.58 Letters | Standard Deviation 7.07 |
| PRN Ranibizumab 0.5 mg | Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 24 | Baseline | 65.1 Letters | Standard Deviation 10.08 |
| PRN Ranibizumab 0.5 mg | Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 24 | Average Change from Baseline | 6.97 Letters | Standard Deviation 6.43 |
| PRN Ranibizumab 0.5 mg | Visual Acuity of the Study Eye: Average Change From Baseline to Month 1 Through Month 24 | Average Month 1 to Month 24 | 72.09 Letters | Standard Deviation 10.141 |
Secondary
Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 12
Visual acuity was assessed at every study visit for the study eye using best correction determined from protocol refraction. The BCVA measurements were taken in a sitting position using ETDRS-like VA testing charts at a starting distance of 4 meters.
Time frame: Baseline, Month 12
Population: Analyzed set included all randomized patients who received at least one application of study treatment and had at least one post baseline efficacy assessment. If missing values occurred without a subsequent observed value, the last observed value was carried forward to subsequent scheduled visits by means of a last observation carried forward.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TE Ranibizumad 0.5 mg and Laser | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 12 | Gain of >= 5 letters | 59.0 Percentage of patients |
| TE Ranibizumad 0.5 mg and Laser | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 12 | Loss of >= 5 letters | 3.4 Percentage of patients |
| TE Ranibizumad 0.5 mg and Laser | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 12 | Gain of >= 15 letters | 19.7 Percentage of patients |
| TE Ranibizumad 0.5 mg and Laser | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 12 | Gain of >= 1 letter | 82.9 Percentage of patients |
| TE Ranibizumad 0.5 mg and Laser | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 12 | Loss of >= 15 letters | 0.0 Percentage of patients |
| TE Ranibizumad 0.5 mg and Laser | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 12 | Loss of >= 10 letters | 0.0 Percentage of patients |
| TE Ranibizumad 0.5 mg and Laser | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 12 | Gain of >= 10 letters | 32.5 Percentage of patients |
| TE Ranibizumab 0.5 mg Alone | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 12 | Gain of >= 15 letters | 30.4 Percentage of patients |
| TE Ranibizumab 0.5 mg Alone | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 12 | Gain of >= 1 letter | 84.8 Percentage of patients |
| TE Ranibizumab 0.5 mg Alone | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 12 | Gain of >= 5 letters | 60.8 Percentage of patients |
| TE Ranibizumab 0.5 mg Alone | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 12 | Gain of >= 10 letters | 42.4 Percentage of patients |
| TE Ranibizumab 0.5 mg Alone | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 12 | Loss of >= 5 letters | 4.0 Percentage of patients |
| TE Ranibizumab 0.5 mg Alone | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 12 | Loss of >= 10 letters | 2.4 Percentage of patients |
| TE Ranibizumab 0.5 mg Alone | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 12 | Loss of >= 15 letters | 1.6 Percentage of patients |
| PRN Ranibizumab 0.5 mg | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 12 | Loss of >= 5 letters | 3.4 Percentage of patients |
| PRN Ranibizumab 0.5 mg | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 12 | Gain of >= 5 letters | 70.1 Percentage of patients |
| PRN Ranibizumab 0.5 mg | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 12 | Loss of >= 15 letters | 0.9 Percentage of patients |
| PRN Ranibizumab 0.5 mg | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 12 | Loss of >= 10 letters | 0.9 Percentage of patients |
| PRN Ranibizumab 0.5 mg | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 12 | Gain of >= 15 letters | 26.5 Percentage of patients |
| PRN Ranibizumab 0.5 mg | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 12 | Gain of >= 10 letters | 39.3 Percentage of patients |
| PRN Ranibizumab 0.5 mg | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 12 | Gain of >= 1 letter | 83.8 Percentage of patients |
Secondary
Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 24
Visual acuity was assessed at every study visit for the study eye using best correction determined from protocol refraction. The BCVA measurements were taken in a sitting position using ETDRS-like VA testing charts at a starting distance of 4 meters.
Time frame: Baseline, 24 month
Population: Analyzed set included all randomized patients who received at least one application of study treatment and had at least one post baseline efficacy assessment. If missing values occurred without a subsequent observed value, the last observed value was carried forward to subsequent scheduled visits by means of a last observation carried forward.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TE Ranibizumad 0.5 mg and Laser | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 24 | Gain of >= 5 letters | 69.2 Percentage of pateints |
| TE Ranibizumad 0.5 mg and Laser | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 24 | Loss of >= 5 letters | 4.3 Percentage of pateints |
| TE Ranibizumad 0.5 mg and Laser | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 24 | Gain of >= 15 letters | 25.6 Percentage of pateints |
| TE Ranibizumad 0.5 mg and Laser | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 24 | Gain of >= 1 letter | 87.2 Percentage of pateints |
| TE Ranibizumad 0.5 mg and Laser | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 24 | Loss of >= 15 letters | 0.9 Percentage of pateints |
| TE Ranibizumad 0.5 mg and Laser | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 24 | Loss of >= 10 letters | 2.6 Percentage of pateints |
| TE Ranibizumad 0.5 mg and Laser | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 24 | Gain of >= 10 letters | 43.6 Percentage of pateints |
| TE Ranibizumab 0.5 mg Alone | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 24 | Gain of >= 15 letters | 28.0 Percentage of pateints |
| TE Ranibizumab 0.5 mg Alone | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 24 | Gain of >= 1 letter | 84.0 Percentage of pateints |
| TE Ranibizumab 0.5 mg Alone | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 24 | Gain of >= 5 letters | 62.4 Percentage of pateints |
| TE Ranibizumab 0.5 mg Alone | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 24 | Gain of >= 10 letters | 40.8 Percentage of pateints |
| TE Ranibizumab 0.5 mg Alone | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 24 | Loss of >= 5 letters | 8.0 Percentage of pateints |
| TE Ranibizumab 0.5 mg Alone | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 24 | Loss of >= 10 letters | 7.2 Percentage of pateints |
| TE Ranibizumab 0.5 mg Alone | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 24 | Loss of >= 15 letters | 4.0 Percentage of pateints |
| PRN Ranibizumab 0.5 mg | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 24 | Loss of >= 5 letters | 5.1 Percentage of pateints |
| PRN Ranibizumab 0.5 mg | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 24 | Gain of >= 5 letters | 76.1 Percentage of pateints |
| PRN Ranibizumab 0.5 mg | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 24 | Loss of >= 15 letters | 2.6 Percentage of pateints |
| PRN Ranibizumab 0.5 mg | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 24 | Loss of >= 10 letters | 3.4 Percentage of pateints |
| PRN Ranibizumab 0.5 mg | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 24 | Gain of >= 15 letters | 30.8 Percentage of pateints |
| PRN Ranibizumab 0.5 mg | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 24 | Gain of >= 10 letters | 45.3 Percentage of pateints |
| PRN Ranibizumab 0.5 mg | Visual Acuity of the Study Eye: Categorized Change From Baseline at Month 24 | Gain of >= 1 letter | 90.6 Percentage of pateints |
Secondary
Visual Acuity of the Study Eye: Change From Baseline at Month 12
Visual acuity was assessed at every study visit for the study eye using best correction determined from protocol refraction. The BCVA measurements were taken in a sitting position using ETDRS-like VA testing charts at a starting distance of 4 meters.
Time frame: Baseline and Month 12
Population: Analyzed set included all randomized patients who received at least one application of study treatment and had at least one post baseline efficacy assessment. If missing values occurred without a subsequent observed value, the last observed value was carried forward to subsequent scheduled visits by means of a last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TE Ranibizumad 0.5 mg and Laser | Visual Acuity of the Study Eye: Change From Baseline at Month 12 | Month 12 | 69.13 Letters | Standard Deviation 11.945 |
| TE Ranibizumad 0.5 mg and Laser | Visual Acuity of the Study Eye: Change From Baseline at Month 12 | Baseline | 62.3 Letters | Standard Deviation 11.5 |
| TE Ranibizumad 0.5 mg and Laser | Visual Acuity of the Study Eye: Change From Baseline at Month 12 | Change from Baseline | 6.79 Letters | Standard Deviation 6.999 |
| TE Ranibizumab 0.5 mg Alone | Visual Acuity of the Study Eye: Change From Baseline at Month 12 | Month 12 | 70.93 Letters | Standard Deviation 11.742 |
| TE Ranibizumab 0.5 mg Alone | Visual Acuity of the Study Eye: Change From Baseline at Month 12 | Baseline | 65.1 Letters | Standard Deviation 10.52 |
| TE Ranibizumab 0.5 mg Alone | Visual Acuity of the Study Eye: Change From Baseline at Month 12 | Change from Baseline | 6.80 Letters | Standard Deviation 8.726 |
| PRN Ranibizumab 0.5 mg | Visual Acuity of the Study Eye: Change From Baseline at Month 12 | Baseline | 65.1 Letters | Standard Deviation 10.08 |
| PRN Ranibizumab 0.5 mg | Visual Acuity of the Study Eye: Change From Baseline at Month 12 | Change from Baseline | 7.44 Letters | Standard Deviation 8.457 |
| PRN Ranibizumab 0.5 mg | Visual Acuity of the Study Eye: Change From Baseline at Month 12 | Month 12 | 72.56 Letters | Standard Deviation 11.592 |
Secondary
Visual Acuity of the Study Eye: Change From Baseline at Month 24
Visual acuity was assessed at every study visit for the study eye using best correction determined from protocol refraction. The BCVA measurements were taken in a sitting position using ETDRS-like VA testing charts at a starting distance of 4 meters.
Time frame: Baseline and Month 24
Population: Analyzed set included all randomized patients who received at least one application of study treatment and had at least one post baseline efficacy assessment. If missing values occurred without a subsequent observed value, the last observed value was carried forward to subsequent scheduled visits by means of a last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TE Ranibizumad 0.5 mg and Laser | Visual Acuity of the Study Eye: Change From Baseline at Month 24 | Month 24 | 70.64 Letters | Standard Deviation 12.315 |
| TE Ranibizumad 0.5 mg and Laser | Visual Acuity of the Study Eye: Change From Baseline at Month 24 | Baseline | 62.3 Letters | Standard Deviation 11.5 |
| TE Ranibizumad 0.5 mg and Laser | Visual Acuity of the Study Eye: Change From Baseline at Month 24 | Change from Baseline | 8.30 Letters | Standard Deviation 8.129 |
| TE Ranibizumab 0.5 mg Alone | Visual Acuity of the Study Eye: Change From Baseline at Month 24 | Month 24 | 70.62 Letters | Standard Deviation 13.481 |
| TE Ranibizumab 0.5 mg Alone | Visual Acuity of the Study Eye: Change From Baseline at Month 24 | Baseline | 64.1 Letters | Standard Deviation 10.52 |
| TE Ranibizumab 0.5 mg Alone | Visual Acuity of the Study Eye: Change From Baseline at Month 24 | Change from Baseline | 6.49 Letters | Standard Deviation 10.854 |
| PRN Ranibizumab 0.5 mg | Visual Acuity of the Study Eye: Change From Baseline at Month 24 | Baseline | 65.1 Letters | Standard Deviation 10.08 |
| PRN Ranibizumab 0.5 mg | Visual Acuity of the Study Eye: Change From Baseline at Month 24 | Change from Baseline | 8.06 Letters | Standard Deviation 8.462 |
| PRN Ranibizumab 0.5 mg | Visual Acuity of the Study Eye: Change From Baseline at Month 24 | Month 24 | 73.18 Letters | Standard Deviation 11.872 |
Secondary
Visual Functioning Questionnaire (VFQ-25) Change From Baseline in Total Score at Month 12 and Month 24
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) was used to measure the influence of visual disability and symptoms on general health. The 12 subscales in the VFQ-25 are general health, general vision, ocular pain, near activities, distance activities, social function, mental health, role difficulties, dependency, driving, color vision, and peripheral vision. For each, the patient was asked to rate their condition on a scale of 1-5 or 1-6, where a low number reflects a better outcome. Each response was recoded per the scoring rules outlined in the National Eye Institute (NEI) VFQ-25 Scoring Algorithm. Under this scoring algorithm , the recoded values range between 0 and 100 and a high score means a better functioning
Time frame: Baseline, Month 12 and Month 24
Population: Analyzed set included all randomized patients who received at least one application of study treatment and had at least one post baseline efficacy assessment. If missing values occurred without a subsequent observed value, the last observed value was carried forward to subsequent scheduled visits by means of a last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TE Ranibizumad 0.5 mg and Laser | Visual Functioning Questionnaire (VFQ-25) Change From Baseline in Total Score at Month 12 and Month 24 | Change from baseline at Month 12 (n=116,122,114) | 4.60 Score on a scale | Standard Deviation 10.905 |
| TE Ranibizumad 0.5 mg and Laser | Visual Functioning Questionnaire (VFQ-25) Change From Baseline in Total Score at Month 12 and Month 24 | Baseline (n=116,122,114) | 75.32 Score on a scale | Standard Deviation 17.317 |
| TE Ranibizumad 0.5 mg and Laser | Visual Functioning Questionnaire (VFQ-25) Change From Baseline in Total Score at Month 12 and Month 24 | Change from baseline at month 24 (n=116,122,114) | 4.06 Score on a scale | Standard Deviation 11.859 |
| TE Ranibizumab 0.5 mg Alone | Visual Functioning Questionnaire (VFQ-25) Change From Baseline in Total Score at Month 12 and Month 24 | Change from baseline at Month 12 (n=116,122,114) | 3.95 Score on a scale | Standard Deviation 10.941 |
| TE Ranibizumab 0.5 mg Alone | Visual Functioning Questionnaire (VFQ-25) Change From Baseline in Total Score at Month 12 and Month 24 | Baseline (n=116,122,114) | 75.47 Score on a scale | Standard Deviation 17.105 |
| TE Ranibizumab 0.5 mg Alone | Visual Functioning Questionnaire (VFQ-25) Change From Baseline in Total Score at Month 12 and Month 24 | Change from baseline at month 24 (n=116,122,114) | 2.31 Score on a scale | Standard Deviation 13.27 |
| PRN Ranibizumab 0.5 mg | Visual Functioning Questionnaire (VFQ-25) Change From Baseline in Total Score at Month 12 and Month 24 | Baseline (n=116,122,114) | 77.07 Score on a scale | Standard Deviation 18.581 |
| PRN Ranibizumab 0.5 mg | Visual Functioning Questionnaire (VFQ-25) Change From Baseline in Total Score at Month 12 and Month 24 | Change from baseline at month 24 (n=116,122,114) | 5.96 Score on a scale | Standard Deviation 12.389 |
| PRN Ranibizumab 0.5 mg | Visual Functioning Questionnaire (VFQ-25) Change From Baseline in Total Score at Month 12 and Month 24 | Change from baseline at Month 12 (n=116,122,114) | 5.41 Score on a scale | Standard Deviation 12.063 |