Retinal Vein Occlusion
Conditions
Keywords
Macular Degeneration, Macular Edema, Retinal Vein Occlusion, Choroidal Neovascularization, Signs and Symptoms, Retinal Degeneration, Retinal Diseases, Eye Diseases, Venous Thrombosis Sensation Disorders, Dexamethasone acetate, Dexamethasone, Dexamethasone 21-phosphate, BB 1101, Anti-Inflammatory Agents, Therapeutic Uses, Vision, Low, Signs, Vision Disorders
Brief summary
The study is intended to characterize the clinical benefit regarding safety and efficacy of a long term treatment with Lucentis in comparison with Ozurdex over an additional 6 months and a 3-month follow-up period, following the initial 6-month treatment in the respective core studies CRFB002EDE17 (NCT01396057) and CRFB002EDE18 (NCT01396083).
Interventions
BIOLOGICALRFB002
0.5 mg/0.05 mL solution to be injected intravitreally. Ranibizumab was formulated as a sterile solution aseptically filled in a sterile glass vial. Each vial contained ranibizumab in an aqueous solution (pH 5.5) with histidine, trehalose and polysorbate 20.
DRUGDexamethasone
Ozurdex (Dexamethasone): intravitreal implant as per commercial label (700 µg Dexamethasone; Dexamethasone was formulated as a rod shaped implant to be inserted into the eye by an applicator. The implant as well as the respective applicator were suitable for single use only. Dexamethasone had to be stored according to label instructions and it had to be kept in a secure locked facility
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have completed the core study assessments at month 6 of study CRFB002EDE17 or CRFB002EDE18, respectively
Exclusion criteria
* Patients who experienced an uncontrollable rise in IOP during the core study CRFB002EDE17 respectively CRFB002EDE18, i.e. IOP could not be decreased to a stable level of \< 25mmHg. * Use of other investigational drugs * Current use or likely need of systemic medications known to be toxic to the lens, retina or optic nerve * History of hypersensitivity to Ranibizumab or Ozurdex or any component of the ranibizumab respectively Ozurdey formulation * Any type of advanced, severe or unstable disease or its treatment, that could interfere with evaluations or put the patient at special risk * Women * who were pregnant or breast feeding (pregnancy defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (\>5 mIU/mL) * who were menstruating and capable of becoming pregnant\* and not practicing a medically approved method of contraception (Pearl Index \<1\*\*)\*\*\* during and up to at least 4 weeks after the end of treatment. A negative pregnancy test (serum) for all women and for girls entering menarche was required with sufficient lead time before randomization * definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels \>40 mIU/mL or 6 weeks post surgical bilateral oophorectomy with or without hysterectomy * examples of particularly reliable methods with Pearl Index (PI) \<1, according to guidelines of Deutsche Gesellschaft für Gynäkologie und Geburtshilfe: * Combination pill with estrogen and gestagen (no mini-pill, PI=0.1-0.9) * Vaginal ring (NuvaRing®, PI=0.65 uncorr.; 0.4 corr.) * Contraceptive patch (EVRA®, PI= 0.72 uncorr.; 0.9 corr.) * Estrogen-free ovulation inhibitors (Cerazette®, PI=0.14) * Progestin-containing contraceptives (Implanon®, PI=0-0.08) * Injectable 3-month depot progestins (PI=0.3-1.4; 0.88 corr.) * Intra-uterine progestin device (Mirena®, PI=0.16)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events as a Measure of Safety and Tolerability | 6 months | The number of participants who experienced Adverse events, serious AE and death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline | 12 month | BCVA score was based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters. An ETDRS visual acuity score of 85 is approximately 20/20. An increased score indicates improvement in acuity. This outcome assessed the percentage of participants who were gaining/losing ≥15, 10 or 5 more letters of visual acuity at month 12 as compared with baseline |
| Change in Central Subfield Thickness (CSRT) From Baseline to 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. |
| Change of Foveal Center Point Thickness (FCPT) From Baseline to Month 12 | Baseline, Month 12 | FCPT (foveal center point thickness) was assessed by central reading center to ensure error- corrected measurements of retinal thickness and volumes, |
| Raw Mean Best Corrected Visual Acuity (BCVA) by Treatment Group | Baseline, 6 months and 12 months | Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. An ETDRS visual acuity score of 85 is approximately 20/20. The range of BCVA (EDTRS) is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement |
| Change in SF-36 Summary Scores | Baseline, month 12 | The SF-36 measures the impact of disease on overall quality of life and consists of eight subscales (physical function, pain, general and mental health, vitality, social function, physical and emotional health) which can be aggregated to derive a physical-component summary score and a mental-component summary score. Scores for each subscale range from 0 to 10, and the composite scores range from 0 to 100, with higher scores indicating better health. A positive change from Baseline score indicates improvement in quality of life. |
| Change in Euro Quality of Life Questionnaire (EQ-5D) VAS Summary Scores | Baseline, month 12 | The Euro Quality of Life Questionnaire (EQ-5D) standardized instrument was utilized to measure health outcomes related to mobility, self care, usual activities, pain/discomfort, and anxiety/depression. Participants self-rate their health on a visual, vertical analogue scale from 0 to 100 where the endpoints are labeled Best imaginable health state (100) and worst imaginable health state (0). |
| Time to the First Retreatment of Both Treatment Arms | 6 months | Time to the first retreatment |
| Change in Mean Visual Function Questionnaire (VFQ-25) | Baseline, 12 months | The VFQ-25 composite and subscale scores range from 0 to 100, a higher score indicating better functioning. 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. The scores on the subscales were added together for a total score, which ranged from 0 to 100. A higher score indicated improvement in quality of life due to vision function. |
Countries
Germany
Participant flow
Recruitment details
A total of 140 patients with (BRVO) completed the core study CRFB002EDE17, and 127 patients with (CRVO) completed the core study CRFB002EDE18. 92 patients with BRVO and 83 patients with CRVO were enrolled into the extension study. A total of 175 patients (113 in the ranibizumab group and 62 in the dexamethasone group) were enrolled
Pre-assignment details
The Full Analysis Sets (FAS) consisted of all patients from the FAS of the respective core study who had received at least one application of study treatment and had at least one post- baseline assessment for BCVA during the extension study. LOCF=last observation carried forward
Participants by arm
| Arm | Count |
|---|---|
| Ranibizumab Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally | 113 |
| Dexamethasone A PRN re-treatment scheme will be applied for the Dexamethasone arm during this extension study, i.e. patients may receive an implant at V1E or later as needed. Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) Minimum period of 5 months in between implantations was required. | 62 |
| Total | 175 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Administrative Problems | 0 | 0 | 1 | 0 |
| Overall Study | Adverse Event | 1 | 1 | 1 | 1 |
| Overall Study | Lack of Efficacy | 0 | 5 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Ranibizumab | Dexamethasone | Total |
|---|---|---|---|
| Age, Continuous | 65.6 Years STANDARD_DEVIATION 9.9 | 63.3 Years STANDARD_DEVIATION 10.3 | 64.8 Years STANDARD_DEVIATION 10.1 |
| Sex: Female, Male Female | 64 Participants | 26 Participants | 90 Participants |
| Sex: Female, Male Male | 49 Participants | 36 Participants | 85 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 | 35 / 52 | 28 / 40 | 45 / 61 | 16 / 22 |
| serious Total, serious adverse events | 2 / 52 | 3 / 40 | 6 / 61 | 1 / 22 |
Outcome results
Primary
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
The number of participants who experienced Adverse events, serious AE and death
Time frame: 6 months
Population: The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ranibizumab (BRVO) | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Adverse event | 35 Participants |
| Ranibizumab (BRVO) | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Death | 0 Participants |
| Ranibizumab (BRVO) | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Serious adverse event | 2 Participants |
| Dexamethasone (BRVO) | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Serious adverse event | 3 Participants |
| Dexamethasone (BRVO) | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Adverse event | 28 Participants |
| Dexamethasone (BRVO) | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Death | 0 Participants |
| Ranibizumab (CRVO) | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Adverse event | 45 Participants |
| Ranibizumab (CRVO) | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Death | 0 Participants |
| Ranibizumab (CRVO) | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Serious adverse event | 6 Participants |
| Dexamethasone (CRVO) | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Serious adverse event | 1 Participants |
| Dexamethasone (CRVO) | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Adverse event | 16 Participants |
| Dexamethasone (CRVO) | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Death | 0 Participants |
Secondary
Change in Central Subfield Thickness (CSRT) From Baseline to 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: Full Analysis Sets (FAS) consisted of all patients from the FAS of the respective core study who had received at least one application of study treatment and had at least one post- baseline assessment for BCVA during the extension study. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ranibizumab (BRVO) | Change in Central Subfield Thickness (CSRT) From Baseline to Month 12 | -288.1 um | Standard Deviation 180.6 |
| Dexamethasone (BRVO) | Change in Central Subfield Thickness (CSRT) From Baseline to Month 12 | -211.5 um | Standard Deviation 199.3 |
| Ranibizumab (CRVO) | Change in Central Subfield Thickness (CSRT) From Baseline to Month 12 | -374.6 um | Standard Deviation 239.8 |
| Dexamethasone (CRVO) | Change in Central Subfield Thickness (CSRT) From Baseline to Month 12 | -360.3 um | Standard Deviation 260.2 |
Secondary
Change in Euro Quality of Life Questionnaire (EQ-5D) VAS Summary Scores
The Euro Quality of Life Questionnaire (EQ-5D) standardized instrument was utilized to measure health outcomes related to mobility, self care, usual activities, pain/discomfort, and anxiety/depression. Participants self-rate their health on a visual, vertical analogue scale from 0 to 100 where the endpoints are labeled Best imaginable health state (100) and worst imaginable health state (0).
Time frame: Baseline, month 12
Population: Full Analysis Sets (FAS) consisted of all patients from the FAS of the respective core study who had received at least one application of study treatment and had at least one post- baseline assessment for BCVA during the extension study. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ranibizumab (BRVO) | Change in Euro Quality of Life Questionnaire (EQ-5D) VAS Summary Scores | 3.3 Score on a scale | Standard Deviation 15.2 |
| Dexamethasone (BRVO) | Change in Euro Quality of Life Questionnaire (EQ-5D) VAS Summary Scores | 2.6 Score on a scale | Standard Deviation 16.9 |
| Ranibizumab (CRVO) | Change in Euro Quality of Life Questionnaire (EQ-5D) VAS Summary Scores | 1.5 Score on a scale | Standard Deviation 16.4 |
| Dexamethasone (CRVO) | Change in Euro Quality of Life Questionnaire (EQ-5D) VAS Summary Scores | 0.2 Score on a scale | Standard Deviation 20.4 |
Secondary
Change in Mean Visual Function Questionnaire (VFQ-25)
The VFQ-25 composite and subscale scores range from 0 to 100, a higher score indicating better functioning. 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. The scores on the subscales were added together for a total score, which ranged from 0 to 100. A higher score indicated improvement in quality of life due to vision function.
Time frame: Baseline, 12 months
Population: Full Analysis Sets (FAS) consisted of all patients from the FAS of the respective core study who had received at least one application of study treatment and had at least one post- baseline assessment for BCVA during the extension study. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ranibizumab (BRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | General Health | -1.4 Scores on a scale | Standard Deviation 15.2 |
| Ranibizumab (BRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Ocular Pain | 5.3 Scores on a scale | Standard Deviation 15.7 |
| Ranibizumab (BRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Overall Composite | 8.1 Scores on a scale | Standard Deviation 10.6 |
| Ranibizumab (BRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Mental Health | 10.2 Scores on a scale | Standard Deviation 14.9 |
| Ranibizumab (BRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Color Vision(BRVO n=52,39) | 0.5 Scores on a scale | Standard Deviation 10.5 |
| Ranibizumab (BRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Near Activities | 13.3 Scores on a scale | Standard Deviation 18.9 |
| Ranibizumab (BRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Peripheral Vision(BRVO n=51,40) | 10.3 Scores on a scale | Standard Deviation 24.1 |
| Ranibizumab (BRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | General Vision | 15.0 Scores on a scale | Standard Deviation 16.7 |
| Ranibizumab (BRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Dependency | 3.2 Scores on a scale | Standard Deviation 9.2 |
| Ranibizumab (BRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Distance Activities | 8.9 Scores on a scale | Standard Deviation 17.5 |
| Ranibizumab (BRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Role Difficulties | 4.8 Scores on a scale | Standard Deviation 26.8 |
| Ranibizumab (BRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Driving (BRVO n=44,31) (CRVO n=42,16) | 11.7 Scores on a scale | Standard Deviation 23.9 |
| Ranibizumab (BRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Social Functioning | 3.4 Scores on a scale | Standard Deviation 16.8 |
| Dexamethasone (BRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Color Vision(BRVO n=52,39) | 1.9 Scores on a scale | Standard Deviation 10.6 |
| Dexamethasone (BRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Dependency | 0.4 Scores on a scale | Standard Deviation 16.6 |
| Dexamethasone (BRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Mental Health | 2.9 Scores on a scale | Standard Deviation 20.4 |
| Dexamethasone (BRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | General Health | 6.3 Scores on a scale | Standard Deviation 18.6 |
| Dexamethasone (BRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Role Difficulties | 10.6 Scores on a scale | Standard Deviation 20.5 |
| Dexamethasone (BRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | General Vision | 9.5 Scores on a scale | Standard Deviation 16.3 |
| Dexamethasone (BRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Overall Composite | 5.5 Scores on a scale | Standard Deviation 11.3 |
| Dexamethasone (BRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Social Functioning | 2.2 Scores on a scale | Standard Deviation 12 |
| Dexamethasone (BRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Ocular Pain | 5.3 Scores on a scale | Standard Deviation 13.8 |
| Dexamethasone (BRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Near Activities | 10.8 Scores on a scale | Standard Deviation 20.6 |
| Dexamethasone (BRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Peripheral Vision(BRVO n=51,40) | 6.9 Scores on a scale | Standard Deviation 23.3 |
| Dexamethasone (BRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Driving (BRVO n=44,31) (CRVO n=42,16) | 4.8 Scores on a scale | Standard Deviation 21.3 |
| Dexamethasone (BRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Distance Activities | 5.6 Scores on a scale | Standard Deviation 15.3 |
| Ranibizumab (CRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | General Vision | 20.0 Scores on a scale | Standard Deviation 17.7 |
| Ranibizumab (CRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Overall Composite | 9.1 Scores on a scale | Standard Deviation 15.5 |
| Ranibizumab (CRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | General Health | 1.7 Scores on a scale | Standard Deviation 18.9 |
| Ranibizumab (CRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Distance Activities | 7.8 Scores on a scale | Standard Deviation 18.3 |
| Ranibizumab (CRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Ocular Pain | 4.2 Scores on a scale | Standard Deviation 20.8 |
| Ranibizumab (CRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Near Activities | 12.3 Scores on a scale | Standard Deviation 20.5 |
| Ranibizumab (CRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Social Functioning | 3.3 Scores on a scale | Standard Deviation 16.7 |
| Ranibizumab (CRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Mental Health | 10.7 Scores on a scale | Standard Deviation 21.7 |
| Ranibizumab (CRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Role Difficulties | 14.6 Scores on a scale | Standard Deviation 29.9 |
| Ranibizumab (CRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Dependency | 5.1 Scores on a scale | Standard Deviation 16.7 |
| Ranibizumab (CRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Driving (BRVO n=44,31) (CRVO n=42,16) | 14.2 Scores on a scale | Standard Deviation 24.6 |
| Ranibizumab (CRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Color Vision(BRVO n=52,39) | 0.4 Scores on a scale | Standard Deviation 17.5 |
| Ranibizumab (CRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Peripheral Vision(BRVO n=51,40) | 11.7 Scores on a scale | Standard Deviation 25 |
| Dexamethasone (CRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Dependency | 4.4 Scores on a scale | Standard Deviation 12.8 |
| Dexamethasone (CRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Distance Activities | 8.3 Scores on a scale | Standard Deviation 23.4 |
| Dexamethasone (CRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Near Activities | 12.3 Scores on a scale | Standard Deviation 23.2 |
| Dexamethasone (CRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Overall Composite | 10.0 Scores on a scale | Standard Deviation 15.9 |
| Dexamethasone (CRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Driving (BRVO n=44,31) (CRVO n=42,16) | 17.7 Scores on a scale | Standard Deviation 25.1 |
| Dexamethasone (CRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Ocular Pain | 3.4 Scores on a scale | Standard Deviation 15 |
| Dexamethasone (CRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | General Vision | 13.6 Scores on a scale | Standard Deviation 23.4 |
| Dexamethasone (CRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Peripheral Vision(BRVO n=51,40) | 14.8 Scores on a scale | Standard Deviation 22.7 |
| Dexamethasone (CRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Color Vision(BRVO n=52,39) | -1.1 Scores on a scale | Standard Deviation 14.4 |
| Dexamethasone (CRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Role Difficulties | 24.4 Scores on a scale | Standard Deviation 27.8 |
| Dexamethasone (CRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Mental Health | 15.1 Scores on a scale | Standard Deviation 18.3 |
| Dexamethasone (CRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | Social Functioning | 2.8 Scores on a scale | Standard Deviation 21.1 |
| Dexamethasone (CRVO) | Change in Mean Visual Function Questionnaire (VFQ-25) | General Health | 5.7 Scores on a scale | Standard Deviation 20.3 |
Secondary
Change in SF-36 Summary Scores
The SF-36 measures the impact of disease on overall quality of life and consists of eight subscales (physical function, pain, general and mental health, vitality, social function, physical and emotional health) which can be aggregated to derive a physical-component summary score and a mental-component summary score. Scores for each subscale range from 0 to 10, and the composite scores range from 0 to 100, with higher scores indicating better health. A positive change from Baseline score indicates improvement in quality of life.
Time frame: Baseline, month 12
Population: Full Analysis Sets (FAS) consisted of all patients from the FAS of the respective core study who had received at least one application of study treatment and had at least one post- baseline assessment for BCVA during the extension study. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ranibizumab (BRVO) | Change in SF-36 Summary Scores | Physical Component(BRVO n=50,39) (CRVO n=58,20) | 1.6 Score on a scale | Standard Deviation 5 |
| Ranibizumab (BRVO) | Change in SF-36 Summary Scores | Mental Component (BRVO n=50,39) (CRVO n=58,20) | 3.3 Score on a scale | Standard Deviation 9.7 |
| Dexamethasone (BRVO) | Change in SF-36 Summary Scores | Mental Component (BRVO n=50,39) (CRVO n=58,20) | 2.1 Score on a scale | Standard Deviation 13.2 |
| Dexamethasone (BRVO) | Change in SF-36 Summary Scores | Physical Component(BRVO n=50,39) (CRVO n=58,20) | 0.2 Score on a scale | Standard Deviation 7 |
| Ranibizumab (CRVO) | Change in SF-36 Summary Scores | Mental Component (BRVO n=50,39) (CRVO n=58,20) | 2.1 Score on a scale | Standard Deviation 9.3 |
| Ranibizumab (CRVO) | Change in SF-36 Summary Scores | Physical Component(BRVO n=50,39) (CRVO n=58,20) | -1.1 Score on a scale | Standard Deviation 8.2 |
| Dexamethasone (CRVO) | Change in SF-36 Summary Scores | Physical Component(BRVO n=50,39) (CRVO n=58,20) | 1.3 Score on a scale | Standard Deviation 7.2 |
| Dexamethasone (CRVO) | Change in SF-36 Summary Scores | Mental Component (BRVO n=50,39) (CRVO n=58,20) | 2.4 Score on a scale | Standard Deviation 12.4 |
Secondary
Change of Foveal Center Point Thickness (FCPT) From Baseline to Month 12
FCPT (foveal center point thickness) was assessed by central reading center to ensure error- corrected measurements of retinal thickness and volumes,
Time frame: Baseline, Month 12
Population: Full Analysis Sets (FAS) consisted of all patients from the FAS of the respective core study who had received at least one application of study treatment and had at least one post- baseline assessment for BCVA during the extension study. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ranibizumab (BRVO) | Change of Foveal Center Point Thickness (FCPT) From Baseline to Month 12 | -341.8 um | Standard Deviation 226.2 |
| Dexamethasone (BRVO) | Change of Foveal Center Point Thickness (FCPT) From Baseline to Month 12 | -252.6 um | Standard Deviation 197.9 |
| Ranibizumab (CRVO) | Change of Foveal Center Point Thickness (FCPT) From Baseline to Month 12 | -439.4 um | Standard Deviation 279.8 |
| Dexamethasone (CRVO) | Change of Foveal Center Point Thickness (FCPT) From Baseline to Month 12 | -432.3 um | Standard Deviation 245.8 |
Secondary
Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline
BCVA score was based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters. An ETDRS visual acuity score of 85 is approximately 20/20. An increased score indicates improvement in acuity. This outcome assessed the percentage of participants who were gaining/losing ≥15, 10 or 5 more letters of visual acuity at month 12 as compared with baseline
Time frame: 12 month
Population: Full Analysis Sets (FAS) consisted of all patients from the FAS of the respective core study who had received at least one application of study treatment and had at least one post- baseline assessment for BCVA during the extension study. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ranibizumab (BRVO) | Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline | Gain≥15 letters | 80.8 Percentage of participants |
| Ranibizumab (BRVO) | Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline | Gain ≥10 letters | 88.5 Percentage of participants |
| Ranibizumab (BRVO) | Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline | Gain ≥5 letters | 100.0 Percentage of participants |
| Ranibizumab (BRVO) | Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline | Loss of ≥15 letters | 0.0 Percentage of participants |
| Ranibizumab (BRVO) | Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline | Loss of ≥10 letters | 0.0 Percentage of participants |
| Ranibizumab (BRVO) | Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline | Loss of ≥5 letters | 0.0 Percentage of participants |
| Dexamethasone (BRVO) | Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline | Loss of ≥5 letters | 10.0 Percentage of participants |
| Dexamethasone (BRVO) | Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline | Loss of ≥15 letters | 7.5 Percentage of participants |
| Dexamethasone (BRVO) | Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline | Gain≥15 letters | 50.0 Percentage of participants |
| Dexamethasone (BRVO) | Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline | Gain ≥5 letters | 80.0 Percentage of participants |
| Dexamethasone (BRVO) | Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline | Gain ≥10 letters | 65.0 Percentage of participants |
| Dexamethasone (BRVO) | Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline | Loss of ≥10 letters | 10.0 Percentage of participants |
| Ranibizumab (CRVO) | Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline | Gain ≥10 letters | 75.0 Percentage of participants |
| Ranibizumab (CRVO) | Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline | Gain ≥5 letters | 86.7 Percentage of participants |
| Ranibizumab (CRVO) | Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline | Loss of ≥15 letters | 0.0 Percentage of participants |
| Ranibizumab (CRVO) | Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline | Loss of ≥5 letters | 3.3 Percentage of participants |
| Ranibizumab (CRVO) | Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline | Loss of ≥10 letters | 0.0 Percentage of participants |
| Ranibizumab (CRVO) | Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline | Gain≥15 letters | 58.3 Percentage of participants |
| Dexamethasone (CRVO) | Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline | Loss of ≥10 letters | 4.5 Percentage of participants |
| Dexamethasone (CRVO) | Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline | Loss of ≥5 letters | 4.5 Percentage of participants |
| Dexamethasone (CRVO) | Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline | Gain ≥10 letters | 68.2 Percentage of participants |
| Dexamethasone (CRVO) | Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline | Loss of ≥15 letters | 4.5 Percentage of participants |
| Dexamethasone (CRVO) | Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline | Gain≥15 letters | 45.5 Percentage of participants |
| Dexamethasone (CRVO) | Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline | Gain ≥5 letters | 77.3 Percentage of participants |
Secondary
Raw Mean Best Corrected Visual Acuity (BCVA) by Treatment Group
Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. An ETDRS visual acuity score of 85 is approximately 20/20. The range of BCVA (EDTRS) is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement
Time frame: Baseline, 6 months and 12 months
Population: FAS consisted of all patients from the FAS of the respective core study who had received at least one application of study treatment and had at least one post- baseline assessment for BCVA during the extension study. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ranibizumab (BRVO) | Raw Mean Best Corrected Visual Acuity (BCVA) by Treatment Group | Baseline | 56.8 Letters read correctly | Standard Deviation 10 |
| Ranibizumab (BRVO) | Raw Mean Best Corrected Visual Acuity (BCVA) by Treatment Group | Month 12 | 79.0 Letters read correctly | Standard Deviation 10.1 |
| Ranibizumab (BRVO) | Raw Mean Best Corrected Visual Acuity (BCVA) by Treatment Group | Month 6 | 77.9 Letters read correctly | Standard Deviation 10.6 |
| Dexamethasone (BRVO) | Raw Mean Best Corrected Visual Acuity (BCVA) by Treatment Group | Baseline | 58.3 Letters read correctly | Standard Deviation 10.8 |
| Dexamethasone (BRVO) | Raw Mean Best Corrected Visual Acuity (BCVA) by Treatment Group | Month 12 | 70.6 Letters read correctly | Standard Deviation 13.9 |
| Dexamethasone (BRVO) | Raw Mean Best Corrected Visual Acuity (BCVA) by Treatment Group | Month 6 | 69.2 Letters read correctly | Standard Deviation 11.9 |
| Ranibizumab (CRVO) | Raw Mean Best Corrected Visual Acuity (BCVA) by Treatment Group | Month 6 | 72.6 Letters read correctly | Standard Deviation 13.5 |
| Ranibizumab (CRVO) | Raw Mean Best Corrected Visual Acuity (BCVA) by Treatment Group | Baseline | 53.8 Letters read correctly | Standard Deviation 15.7 |
| Ranibizumab (CRVO) | Raw Mean Best Corrected Visual Acuity (BCVA) by Treatment Group | Month 12 | 72.6 Letters read correctly | Standard Deviation 15.8 |
| Dexamethasone (CRVO) | Raw Mean Best Corrected Visual Acuity (BCVA) by Treatment Group | Baseline | 53.2 Letters read correctly | Standard Deviation 16.1 |
| Dexamethasone (CRVO) | Raw Mean Best Corrected Visual Acuity (BCVA) by Treatment Group | Month 12 | 66.6 Letters read correctly | Standard Deviation 22.3 |
| Dexamethasone (CRVO) | Raw Mean Best Corrected Visual Acuity (BCVA) by Treatment Group | Month 6 | 64.1 Letters read correctly | Standard Deviation 24 |
Secondary
Time to the First Retreatment of Both Treatment Arms
Time to the first retreatment
Time frame: 6 months
Population: The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ranibizumab (BRVO) | Time to the First Retreatment of Both Treatment Arms | 37 Days |
| Dexamethasone (BRVO) | Time to the First Retreatment of Both Treatment Arms | NA Days |
| Ranibizumab (CRVO) | Time to the First Retreatment of Both Treatment Arms | 62 Days |
| Dexamethasone (CRVO) | Time to the First Retreatment of Both Treatment Arms | NA Days |