Neovascular Age-related Macular Degeneration
Conditions
Keywords
wet age-related macular degeneration (AMD), ranibizumab, aflibercept, Best Corrected Visual Acuity (BCVA), Spectral Domain Optical Coherence Tomography (SD-OCT)
Brief summary
The purpose of this study was to compare the efficacy of 0.5 mg ranibizumab versus 2 mg aflibercept bimonthly intravitreal injections on retinal thickness stability.
Detailed description
Patients attended 14 scheduled study visits during 12 months.
Interventions
DRUGRanibizumab
0.5 mg intravitreal injection
DRUGAflibercept
2 mg intravitreal injection
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
The reading center was masked for treatment assignment in order to ensure unbiased evaluation of the primary, secondary and exploratory objectives that were determined by SDOCT, autofluorescence imaging, and microperimetry and multifocal ERG (where available). When communicating with the reading center study centers had to be vigilant not to unblind the reading center to the treatment. Site staff performing the assessments of BCVA, contrast sensitivity (where possible), VFQ25 and IReST (reading speed) were also masked to the identity of the treatment. The central laboratory used for analysis of all specimens collected for biomarker assessment were blinded to the identity of the treatment.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Visual impairment predominantly due to neovascular AMD Active * Newly diagnosed, untreated, angiographically documented choroidal neovascularization (CNV) lesion Key
Exclusion criteria
* Stroke or myocardial infarction less than 3 Months prior to study entry * Active injection or inflammation of either eye at the time of study entry * Any type of systemic disease (or received treatment for it), including any medical condition (controlled or uncontrolled) that were to be expected to progress, recur, or change to an extent which could bias the assessment of the clinical status of the patient to a significant degree or put the patient at special risk
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean of the Absolute Values of CSRT Difference Month 3 to Month 6 | Month 3, Month 4, Month 5, Month 6 | The thickness of the retina was measured by Spectral Domain Optical Coherence Topography (SD-OCT). The mean of the absolute values of the CSRT difference between Month 3 and 4, Month 4 and 5, and Month 5 and 6 was calculated (ie, CSRT fluctuation). A lower average CSRT fluctuation demonstrates greater retinal stability. One eye (study eye) contributed to the analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Best Corrected Visual Acuity (BCVA) Score Measured in ETDRS Letters at Month 12 | Month 12 | Visual acuity was assessed in a sitting position with refraction using ETDRS-like visual acuity testing charts at an initial testing distance of 4 meters. A higher score indicates better visual acuity. ETDRS scale ranges from 0-100 letters. A score of 65 to 70 letters represents a low to moderate visual acuity |
| IREST at Month 12 | Month 12 | Number of incorrectly read words (IREST) was assessed using International Reading Speed Texts (IResT) and measured in words per minute. |
| National Eye Institute Visual Functioning Questionnaire Composite Score (VFQ-25) at Month 12 | Month 12 | Vision-related quality of life was assessed by the patient using the National Eye Institute Visual Function Questionnaire. The scores of 12 subscales (general health, general vision, ocular pain, near activities, distance activities, social function, mental health, role difficulties, dependency, driving, color vision, and peripheral vision) were added together for a total (composite) score, which ranged from 0 to 100. A higher score indicates poorer function. |
| Correlations Between CSRT Fluctuation (Month 3 to 6) and Functional Outcomes at Month 12 (Full Analysis Set) | Month 3 to Month 6, Month 12 | Correlation coefficient calculated based on Pearson's correlation between each corresponding parameter and CSRT stability. |
Countries
Austria, Belgium, Denmark, France, Germany, Netherlands, Norway, Portugal, Sweden, Switzerland
Participant flow
Recruitment details
Patients were recruited from 6 sites in Austria, 2 sites in Belgium, 2 sites in Denmark and 5 sites from France.
Pre-assignment details
This reporting group included all patients randomized to one of the treatment arms (Randomized Set) The Full Analysis Set (FAS) consisted of all patients who received at least one application of study treatment and had at least one post-baseline assessment for SD-OCT.
Participants by arm
| Arm | Count |
|---|---|
| Ranibizumab 0.5 mg intravitreal injections of ranibizumab monthly until maximum stable BCVA with retreatment based on BCVA loss and/or SD-OCT signs of wet AMD disease activity. | 353 |
| Aflibercept 2 mg intravitreal injections of aflibercept monthly for the first 3 months, followed by 2 mg intravitreal injections once every 2 months (current EU SmPC label) | 354 |
| Total | 707 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | administrative problems | 0 | 2 |
| Overall Study | Adverse Event | 12 | 12 |
| Overall Study | Death | 1 | 3 |
| Overall Study | Lack of Efficacy | 13 | 10 |
| Overall Study | Lost to Follow-up | 4 | 7 |
| Overall Study | Withdrawal by Subject | 13 | 8 |
Baseline characteristics
| Characteristic | Ranibizumab | Aflibercept | Total |
|---|---|---|---|
| Age, Continuous | 77.3 years STANDARD_DEVIATION 7.53 | 78.0 years STANDARD_DEVIATION 7.21 | 77.7 years STANDARD_DEVIATION 7.38 |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Caucasian | 350 Participants | 352 Participants | 702 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Female | 210 Participants | 218 Participants | 428 Participants |
| Sex: Female, Male Male | 143 Participants | 136 Participants | 279 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 356 | 3 / 356 |
| other Total, other adverse events | 156 / 356 | 156 / 356 |
| serious Total, serious adverse events | 67 / 356 | 74 / 356 |
Outcome results
Primary
Mean of the Absolute Values of CSRT Difference Month 3 to Month 6
The thickness of the retina was measured by Spectral Domain Optical Coherence Topography (SD-OCT). The mean of the absolute values of the CSRT difference between Month 3 and 4, Month 4 and 5, and Month 5 and 6 was calculated (ie, CSRT fluctuation). A lower average CSRT fluctuation demonstrates greater retinal stability. One eye (study eye) contributed to the analysis.
Time frame: Month 3, Month 4, Month 5, Month 6
Population: FAS. Number analyzed is the number of patients with a measurement
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ranibizumab | Mean of the Absolute Values of CSRT Difference Month 3 to Month 6 | 25.16 micrometers | Standard Error 2.584 |
| Aflibercept | Mean of the Absolute Values of CSRT Difference Month 3 to Month 6 | 29.28 micrometers | Standard Error 2.62 |
p-value: 0.185ANOVA
Secondary
Correlations Between CSRT Fluctuation (Month 3 to 6) and Functional Outcomes at Month 12 (Full Analysis Set)
Correlation coefficient calculated based on Pearson's correlation between each corresponding parameter and CSRT stability.
Time frame: Month 3 to Month 6, Month 12
Population: Full Analysis Set with measure. No statistical analysis was performed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ranibizumab | Correlations Between CSRT Fluctuation (Month 3 to 6) and Functional Outcomes at Month 12 (Full Analysis Set) | Total BCVA Score | -0.2194 correlation coefficient |
| Ranibizumab | Correlations Between CSRT Fluctuation (Month 3 to 6) and Functional Outcomes at Month 12 (Full Analysis Set) | IREST reading speed (words/minute) | 0.0889 correlation coefficient |
| Ranibizumab | Correlations Between CSRT Fluctuation (Month 3 to 6) and Functional Outcomes at Month 12 (Full Analysis Set) | VFQ-25 composite score | 0.1064 correlation coefficient |
| Aflibercept | Correlations Between CSRT Fluctuation (Month 3 to 6) and Functional Outcomes at Month 12 (Full Analysis Set) | Total BCVA Score | 0.0155 correlation coefficient |
| Aflibercept | Correlations Between CSRT Fluctuation (Month 3 to 6) and Functional Outcomes at Month 12 (Full Analysis Set) | IREST reading speed (words/minute) | 0.0450 correlation coefficient |
| Aflibercept | Correlations Between CSRT Fluctuation (Month 3 to 6) and Functional Outcomes at Month 12 (Full Analysis Set) | VFQ-25 composite score | 0.0847 correlation coefficient |
Secondary
IREST at Month 12
Number of incorrectly read words (IREST) was assessed using International Reading Speed Texts (IResT) and measured in words per minute.
Time frame: Month 12
Population: FAS with measurement at Month 12. No statistical analysis was performed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ranibizumab | IREST at Month 12 | 5.7 incorrect words per minute | Standard Deviation 21.19 |
| Aflibercept | IREST at Month 12 | 6.1 incorrect words per minute | Standard Deviation 21.86 |
Secondary
National Eye Institute Visual Functioning Questionnaire Composite Score (VFQ-25) at Month 12
Vision-related quality of life was assessed by the patient using the National Eye Institute Visual Function Questionnaire. The scores of 12 subscales (general health, general vision, ocular pain, near activities, distance activities, social function, mental health, role difficulties, dependency, driving, color vision, and peripheral vision) were added together for a total (composite) score, which ranged from 0 to 100. A higher score indicates poorer function.
Time frame: Month 12
Population: FAS with measurement at Month 12. No statistical analysis was performed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ranibizumab | National Eye Institute Visual Functioning Questionnaire Composite Score (VFQ-25) at Month 12 | 80.0 units on a scale | Standard Deviation 14.43 |
| Aflibercept | National Eye Institute Visual Functioning Questionnaire Composite Score (VFQ-25) at Month 12 | 79.1 units on a scale | Standard Deviation 14.95 |
Secondary
Total Best Corrected Visual Acuity (BCVA) Score Measured in ETDRS Letters at Month 12
Visual acuity was assessed in a sitting position with refraction using ETDRS-like visual acuity testing charts at an initial testing distance of 4 meters. A higher score indicates better visual acuity. ETDRS scale ranges from 0-100 letters. A score of 65 to 70 letters represents a low to moderate visual acuity
Time frame: Month 12
Population: FAS with measurement at visit Month 12. No statistical analysis was performed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ranibizumab | Total Best Corrected Visual Acuity (BCVA) Score Measured in ETDRS Letters at Month 12 | 66.4 letters | Standard Deviation 18.1 |
| Aflibercept | Total Best Corrected Visual Acuity (BCVA) Score Measured in ETDRS Letters at Month 12 | 68 letters | Standard Deviation 17.62 |