Age-related Macular Degeneration (AMD)
Conditions
Brief summary
The purpose of this study is to determine the efficacy and safety of the biosimilar ranibizumab FYB201 in comparison to Lucentis in patients with neovascular age-related macular degeneration.
Interventions
BIOLOGICALranibizumab
Sponsors
Bioeq GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 50 years of either gender * Signed informed consent form must be obtained before any study-related procedure is performed * Willingness and ability to undertake all scheduled visits and assessments * Women must be postmenopausal or surgically sterile * Newly diagnosed, angiographically documented, primary active Choroidal Neovascularization (CNV) lesion secondary to age-related macular degeneration (AMD) * Sufficiently clear ocular media and adequate pupillary dilation to permit good quality ocular imaging * Best-corrected Visual Acuity (BCVA) in the study eye, determined by standardized Early Treatment Diabetic Retinopathy Study (ETDRS) testing, between 20/32 (0.63) and 20/100 (0.2) Snellen equivalent * Foveal Center Point (FCP) retinal thickness in at Screening ≥ 350 µm * BCVA in the fellow eye, determined by standardized ETDRS testing, at least 20/100 (0.2) Snellen equivalent
Exclusion criteria
* Employees of clinical study sites, individuals directly involved with the conduct of the study or immediate family members thereof, prisoners, and persons who are legally institutionalized * Any previous treatment with intravitreal (IVT) anti-vascular endothelial growth factor (VEGF) agent in either eye * History of vitrectomy, macular surgery or other surgical intervention for AMD in the study eye * History of IVT or periocular injections of corticosteroids or device implantation within six months prior to Screening in the study eye * Prior treatment with verteporfin (photodynamic therapy), transpupillary thermotherapy, radiation therapy, or retinal laser treatment (e.g. focal laser photocoagulation) in the study eye * Topical ocular corticosteroids administered for at least 30 consecutive days within three months prior to Screening * Any other intraocular surgery (including cataract surgery) in the study eye within three months prior to Screening * Sub- or intra-retinal hemorrhage that comprises more than 50% of the entire lesion in the study eye * Fibrosis or atrophy involving the center of the fovea or influencing central visual function in the study eye * CNV in either eye due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia * Retinal pigment epithelial tear involving the macula in the study eye * History of full-thickness macular hole in the study eye * History of retinal detachment in the study eye * Current vitreous hemorrhage in the study eye * Spherical equivalent of the refractive error in the study eye demonstrating more than 8 diopters of myopia * For patients who have undergone prior refractive or cataract surgery in the study eye, the preoperative refractive error in the study eye cannot exceed 8 diopters of myopia * History of corneal transplant in the study eye * Aphakia in the study eye. Absence of an intact posterior capsule is allowed if it occurred as a result of Yttrium-Aluminium-Garnet (YAG) laser posterior capsulotomy in association with prior posterior chamber intraocular lens (IOL) implantation * Active or recent (within 4 weeks) intraocular inflammation of clinical significance in the study eye such as active infections of the anterior segment (excluding mild blepharitis) including conjunctivitis, keratitis, scleritis, uveitis or endophthalmitis * Uncontrolled hypertension or glaucoma in the study eye (defined as intraocular pressure (IOP) ≥30 mm Hg, despite treatment with anti-glaucomatous medication) * Ocular disorders in the study eye (i.e. retinal detachment, pre-retinal membrane of the macula or cataract with significant impact on visual acuity) at the time of enrollment that may confound interpretation of study results and compromise visual acuity * Any concurrent intraocular condition in the study eye (e.g. glaucoma, cataract or diabetic retinopathy) that, in the opinion of the Investigator, would either require surgical intervention during the study to prevent or treat visual loss that might result from that condition or affect interpretation of study results. * Use of other investigational drugs (excluding vitamins, minerals) within 30 days or 5 half-lives from Screening, whichever is longer * Any type of advanced, severe or unstable disease, including any medical condition (controlled or uncontrolled) that could be expected to progress, recur, or change to such an extent that it may bias the assessment of the clinical status of the patient to a significant degree or put the patient at special risk * Stroke or myocardial infarction within three months prior to Screening * Presence of uncontrolled systolic blood pressure \> 160 mmHg or uncontrolled diastolic blood pressure \> 100 mmHg * Known hypersensitivity to the investigational drug (ranibizumab or any component of the ranibizumab formulation) or to drugs of similar chemical class or to fluorescein or any other component of fluorescein formulation * Current or planned use of systemic medications known to be toxic to the lens, retina or optic nerve, including deferoxamine, chloroquine/hydroxychloroquine (Plaquenil®), tamoxifen, phenothiazines and ethambutol * History of recurrent significant infections and/or current treatment for active systemic infection * Pregnancy or lactation * Systemic treatment with high doses of corticosteroids (administration of \>10 mg/day of prednisolone equivalent) during the last six months prior to Screening * Inability to comply with study or follow-up procedures * Any diagnosis and/or signs of nAMD requiring treatment with an IVT anti-VEGF agent (e.g. aflibercept, bevacizumab, ranibizumab) within the screening period or at study treatment initiation (Visit 1) in the fellow eye
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Best Corrected Visual Acuity (BCVA) [Letters] After 8 Weeks | Baseline and Week 8 | The primary endpoint was the absolute change from baseline in BCVA by Early Treatment Diabetic Retinopathy Study (ETDRS) letters after 2 months (8 weeks) of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Best Corrected Visual Acuity (BCVA) [Letters] After 48 Weeks | Baseline and Week 48 | Absolute change from baseline in BCVA by Early Treatment Diabetic Retinopathy Study (ETDRS) letters after 48 weeks of treatment. |
| Change From Baseline in Best Corrected Visual Acuity (BCVA) [Letters] After 12 Months | Baseline and 12 Months | Absolute change from baseline in BCVA by Early Treatment Diabetic Retinopathy Study (ETDRS) letters after 12 months, calculated as the average of the changes from baseline to Week 40, to Week 44 and to Week 48. |
| Change in Foveal Centre Point (FCP) Retinal Thickness From Baseline to Week 24 | Baseline and Week 24 | Absolute change in Foveal Centre Point (FCP) retinal thickness \[µm\] from baseline to Week 24 |
| Change in Foveal Centre Point (FCP) Retinal Thickness From Baseline to Week 48 | Baseline and Week 48 | Absolute change in Foveal Centre Point (FCP) retinal thickness \[µm\] from baseline to Week 48 |
| Change in Foveal Central Subfield (FCS) Retinal Thickness From Baseline to Week 24 | Baseline and Week 24 | Absolute change in Foveal Central Subfield (FCS) retinal thickness \[µm\] from baseline to Week 24 |
| Change in Foveal Central Subfield (FCS) Retinal Thickness From Baseline to Week 48 | Baseline and Week 48 | Absolute change in Foveal Central Subfield (FCS) retinal thickness \[µm\] from baseline to Week 48 |
| Change in Total Lesion Area From Baseline to Week 24 | Baseline and Week 24 | Absolute change in total lesion area \[mm²\] from baseline to Week 24 |
| Change From Baseline in Best Corrected Visual Acuity (BCVA) [Letters] After 24 Weeks | Baseline and Week 24 | Absolute change from baseline in BCVA by Early Treatment Diabetic Retinopathy Study (ETDRS) letters after 24 weeks of treatment. |
| Change in NEI VFQ-25 Composite Score From Baseline to Week 24 | Baseline and Week 24 | Absolute change from baseline to Week 24 in vision-related functioning and well-being measured by the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25) composite score. The NEI VFQ-25 is a 25 question quality of life questionnaire with possible item scores between 0 and 100. Higher scores represent better functioning. The composite score is calculated as average over all non-missing item scores. |
| Change in NEI VFQ-25 Composite Score From Baseline to Week 48 | Baseline and Week 48 | Absolute change from baseline to Week 48 in vision-related functioning and well-being measured by the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25) composite score. The NEI VFQ-25 is a 25 question quality of life questionnaire with possible item scores between 0 and 100. Higher scores represent better functioning. The composite score is calculated as average over all non-missing item scores. |
| Active CNV Leakage at Week 24 | Baseline and Week 24 | Number and percentage of patients with active CNV leakage at Week 24 |
| Active CNV Leakage at Week 48 | Baseline and Week 48 | Number and percentage of patients with active CNV leakage at Week 48 |
| Fluid-free Macula at Each Visit | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 | Number and percentage of patients with fluid-free macula at each visit |
| Anti-drug Antibodies by Scheduled eCRF Visit | Baseline and Weeks 1, 4, 12, 24, 48 | Frequency of patients with anti-drug antibodies (ADAs) by scheduled eCRF visit |
| Anti-drug Antibodies Pre- and Post-first Dosing | Baseline and up to Week 48 | Number and percentage of patients with detection of anti-drug antibodies (ADAs) pre-first dosing and post-first dosing (combination of all ADA assessments after first injection of study medication). |
| Change in Total Lesion Area From Baseline to Week 48 | Baseline and Week 48 | Absolute change in total lesion area \[mm²\] from baseline to Week 48 |
Countries
Austria, Czechia, France, Germany, Hungary, Israel, Italy, Poland, Russia, Spain, Ukraine, United Kingdom
Participant flow
Pre-assignment details
All 712 patients were screened for eligibility before participating in the active treatment phase of the study, resulting in 722 screenings due to 10 rescreenings. Subjects were not to be entered to trial treatment if any of the eligibility criteria were violated. Of the 712 distinct patients, 477 patients were randomized and treated.
Participants by arm
| Arm | Count |
|---|---|
| FYB201 Patients received FYB201 at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections | 238 |
| Lucentis Patients received Lucentis (ranibizumab) at a dose of 0.5mg (0.05mL of a 10mg/mL solution) as twelve monthly intravitreal injections | 239 |
| Total | 477 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Death | 2 | 1 |
| Overall Study | Lost to Follow-up | 3 | 1 |
| Overall Study | Need for alternative treatment | 1 | 0 |
| Overall Study | Other Reason | 2 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 8 |
Baseline characteristics
| Characteristic | Lucentis | Total | FYB201 |
|---|---|---|---|
| Age, Continuous | 76.1 years STANDARD_DEVIATION 7.84 | 75.5 years STANDARD_DEVIATION 8.07 | 74.9 years STANDARD_DEVIATION 8.26 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 6 Participants | 2 Participants |
| Race (NIH/OMB) White | 233 Participants | 469 Participants | 236 Participants |
| Sex: Female, Male Female | 134 Participants | 269 Participants | 135 Participants |
| Sex: Female, Male Male | 105 Participants | 208 Participants | 103 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 238 | 1 / 239 |
| other Total, other adverse events | 149 / 238 | 161 / 239 |
| serious Total, serious adverse events | 19 / 238 | 32 / 239 |
Outcome results
Primary
Change From Baseline in Best Corrected Visual Acuity (BCVA) [Letters] After 8 Weeks
The primary endpoint was the absolute change from baseline in BCVA by Early Treatment Diabetic Retinopathy Study (ETDRS) letters after 2 months (8 weeks) of treatment.
Time frame: Baseline and Week 8
Population: FAS\_US: The FAS\_US was based on the intention to treat principle (i.e., patients were analyzed according to their randomized treatment irrespective of the treatment they actually received) and included all patients who received at least one injection of IMP, and for whom BCVA results at least after 1 month were available and who had a screening BCVA between 20/32 and 20/100 Snellen equivalent in the study eye.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FYB201 | Change From Baseline in Best Corrected Visual Acuity (BCVA) [Letters] After 8 Weeks | 5.1 letters | Standard Deviation 7.52 |
| Lucentis | Change From Baseline in Best Corrected Visual Acuity (BCVA) [Letters] After 8 Weeks | 5.6 letters | Standard Deviation 8.63 |
| Total | Change From Baseline in Best Corrected Visual Acuity (BCVA) [Letters] After 8 Weeks | 5.4 letters | Standard Deviation 8.1 |
Comparison: The hypothesis of biosimilarity of FYB201 and Lucentis was tested with a two-sided equivalence test with an equivalence margin of 3 ETDRS letters. An ANCOVA model was used with the change in BCVA between baseline and Week 8 as the dependent variable, the baseline BCVA as covariate, and the country and the treatment group as fixed effects.90% CI: [-1.6, 0.9]ANCOVA
Secondary
Active CNV Leakage at Week 24
Number and percentage of patients with active CNV leakage at Week 24
Time frame: Baseline and Week 24
Population: FAS\_US
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| FYB201 | Active CNV Leakage at Week 24 | CNV leakage | 115 Participants |
| FYB201 | Active CNV Leakage at Week 24 | No CNV leakage | 106 Participants |
| Lucentis | Active CNV Leakage at Week 24 | CNV leakage | 111 Participants |
| Lucentis | Active CNV Leakage at Week 24 | No CNV leakage | 108 Participants |
| Total | Active CNV Leakage at Week 24 | CNV leakage | 226 Participants |
| Total | Active CNV Leakage at Week 24 | No CNV leakage | 214 Participants |
Secondary
Active CNV Leakage at Week 48
Number and percentage of patients with active CNV leakage at Week 48
Time frame: Baseline and Week 48
Population: FAS\_US
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| FYB201 | Active CNV Leakage at Week 48 | CNV leakage | 119 Participants |
| FYB201 | Active CNV Leakage at Week 48 | No CNV leakage | 92 Participants |
| Lucentis | Active CNV Leakage at Week 48 | CNV leakage | 115 Participants |
| Lucentis | Active CNV Leakage at Week 48 | No CNV leakage | 81 Participants |
| Total | Active CNV Leakage at Week 48 | CNV leakage | 234 Participants |
| Total | Active CNV Leakage at Week 48 | No CNV leakage | 173 Participants |
Secondary
Anti-drug Antibodies by Scheduled eCRF Visit
Frequency of patients with anti-drug antibodies (ADAs) by scheduled eCRF visit
Time frame: Baseline and Weeks 1, 4, 12, 24, 48
Population: SAF
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| FYB201 | Anti-drug Antibodies by Scheduled eCRF Visit | Baseline | Negative anti-drug antibodies | 234 Participants |
| FYB201 | Anti-drug Antibodies by Scheduled eCRF Visit | Week 4 | Positive anti-drug antibodies | 2 Participants |
| FYB201 | Anti-drug Antibodies by Scheduled eCRF Visit | Week 48 | Positive anti-drug antibodies | 9 Participants |
| FYB201 | Anti-drug Antibodies by Scheduled eCRF Visit | Week 24 | Negative anti-drug antibodies | 219 Participants |
| FYB201 | Anti-drug Antibodies by Scheduled eCRF Visit | Week 4 | Negative anti-drug antibodies | 224 Participants |
| FYB201 | Anti-drug Antibodies by Scheduled eCRF Visit | Baseline | Positive anti-drug antibodies | 0 Participants |
| FYB201 | Anti-drug Antibodies by Scheduled eCRF Visit | Week 48 | Negative anti-drug antibodies | 220 Participants |
| FYB201 | Anti-drug Antibodies by Scheduled eCRF Visit | Week 12 | Positive anti-drug antibodies | 1 Participants |
| FYB201 | Anti-drug Antibodies by Scheduled eCRF Visit | Week 1 | Negative anti-drug antibodies | 28 Participants |
| FYB201 | Anti-drug Antibodies by Scheduled eCRF Visit | Week 1 | Positive anti-drug antibodies | 0 Participants |
| FYB201 | Anti-drug Antibodies by Scheduled eCRF Visit | Week 12 | Negative anti-drug antibodies | 225 Participants |
| FYB201 | Anti-drug Antibodies by Scheduled eCRF Visit | Week 24 | Positive anti-drug antibodies | 6 Participants |
| Lucentis | Anti-drug Antibodies by Scheduled eCRF Visit | Week 12 | Negative anti-drug antibodies | 224 Participants |
| Lucentis | Anti-drug Antibodies by Scheduled eCRF Visit | Week 24 | Positive anti-drug antibodies | 6 Participants |
| Lucentis | Anti-drug Antibodies by Scheduled eCRF Visit | Week 24 | Negative anti-drug antibodies | 219 Participants |
| Lucentis | Anti-drug Antibodies by Scheduled eCRF Visit | Week 48 | Positive anti-drug antibodies | 12 Participants |
| Lucentis | Anti-drug Antibodies by Scheduled eCRF Visit | Week 1 | Negative anti-drug antibodies | 29 Participants |
| Lucentis | Anti-drug Antibodies by Scheduled eCRF Visit | Week 48 | Negative anti-drug antibodies | 213 Participants |
| Lucentis | Anti-drug Antibodies by Scheduled eCRF Visit | Week 4 | Positive anti-drug antibodies | 2 Participants |
| Lucentis | Anti-drug Antibodies by Scheduled eCRF Visit | Baseline | Negative anti-drug antibodies | 233 Participants |
| Lucentis | Anti-drug Antibodies by Scheduled eCRF Visit | Week 4 | Negative anti-drug antibodies | 226 Participants |
| Lucentis | Anti-drug Antibodies by Scheduled eCRF Visit | Baseline | Positive anti-drug antibodies | 5 Participants |
| Lucentis | Anti-drug Antibodies by Scheduled eCRF Visit | Week 12 | Positive anti-drug antibodies | 2 Participants |
| Lucentis | Anti-drug Antibodies by Scheduled eCRF Visit | Week 1 | Positive anti-drug antibodies | 0 Participants |
| Total | Anti-drug Antibodies by Scheduled eCRF Visit | Week 48 | Negative anti-drug antibodies | 433 Participants |
| Total | Anti-drug Antibodies by Scheduled eCRF Visit | Baseline | Positive anti-drug antibodies | 5 Participants |
| Total | Anti-drug Antibodies by Scheduled eCRF Visit | Baseline | Negative anti-drug antibodies | 467 Participants |
| Total | Anti-drug Antibodies by Scheduled eCRF Visit | Week 1 | Positive anti-drug antibodies | 0 Participants |
| Total | Anti-drug Antibodies by Scheduled eCRF Visit | Week 1 | Negative anti-drug antibodies | 57 Participants |
| Total | Anti-drug Antibodies by Scheduled eCRF Visit | Week 4 | Positive anti-drug antibodies | 4 Participants |
| Total | Anti-drug Antibodies by Scheduled eCRF Visit | Week 4 | Negative anti-drug antibodies | 450 Participants |
| Total | Anti-drug Antibodies by Scheduled eCRF Visit | Week 12 | Positive anti-drug antibodies | 3 Participants |
| Total | Anti-drug Antibodies by Scheduled eCRF Visit | Week 12 | Negative anti-drug antibodies | 449 Participants |
| Total | Anti-drug Antibodies by Scheduled eCRF Visit | Week 24 | Positive anti-drug antibodies | 12 Participants |
| Total | Anti-drug Antibodies by Scheduled eCRF Visit | Week 24 | Negative anti-drug antibodies | 438 Participants |
| Total | Anti-drug Antibodies by Scheduled eCRF Visit | Week 48 | Positive anti-drug antibodies | 21 Participants |
Secondary
Anti-drug Antibodies Pre- and Post-first Dosing
Number and percentage of patients with detection of anti-drug antibodies (ADAs) pre-first dosing and post-first dosing (combination of all ADA assessments after first injection of study medication).
Time frame: Baseline and up to Week 48
Population: SAF
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| FYB201 | Anti-drug Antibodies Pre- and Post-first Dosing | Pre-first dosing | Negative anti-drug antibodies | 232 Participants |
| FYB201 | Anti-drug Antibodies Pre- and Post-first Dosing | Post-first dosing | Positive anti-drug antibodies | 14 Participants |
| FYB201 | Anti-drug Antibodies Pre- and Post-first Dosing | Pre-first dosing | Positive anti-drug antibodies | 0 Participants |
| FYB201 | Anti-drug Antibodies Pre- and Post-first Dosing | Post-first dosing | Negative anti-drug antibodies | 223 Participants |
| Lucentis | Anti-drug Antibodies Pre- and Post-first Dosing | Pre-first dosing | Negative anti-drug antibodies | 231 Participants |
| Lucentis | Anti-drug Antibodies Pre- and Post-first Dosing | Pre-first dosing | Positive anti-drug antibodies | 5 Participants |
| Lucentis | Anti-drug Antibodies Pre- and Post-first Dosing | Post-first dosing | Positive anti-drug antibodies | 14 Participants |
| Lucentis | Anti-drug Antibodies Pre- and Post-first Dosing | Post-first dosing | Negative anti-drug antibodies | 224 Participants |
| Total | Anti-drug Antibodies Pre- and Post-first Dosing | Post-first dosing | Positive anti-drug antibodies | 28 Participants |
| Total | Anti-drug Antibodies Pre- and Post-first Dosing | Pre-first dosing | Positive anti-drug antibodies | 5 Participants |
| Total | Anti-drug Antibodies Pre- and Post-first Dosing | Pre-first dosing | Negative anti-drug antibodies | 463 Participants |
| Total | Anti-drug Antibodies Pre- and Post-first Dosing | Post-first dosing | Negative anti-drug antibodies | 447 Participants |
Secondary
Change From Baseline in Best Corrected Visual Acuity (BCVA) [Letters] After 12 Months
Absolute change from baseline in BCVA by Early Treatment Diabetic Retinopathy Study (ETDRS) letters after 12 months, calculated as the average of the changes from baseline to Week 40, to Week 44 and to Week 48.
Time frame: Baseline and 12 Months
Population: FAS\_US
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FYB201 | Change From Baseline in Best Corrected Visual Acuity (BCVA) [Letters] After 12 Months | 7.8 letters | Standard Deviation 11.19 |
| Lucentis | Change From Baseline in Best Corrected Visual Acuity (BCVA) [Letters] After 12 Months | 7.9 letters | Standard Deviation 11.01 |
| Total | Change From Baseline in Best Corrected Visual Acuity (BCVA) [Letters] After 12 Months | 7.8 letters | Standard Deviation 11.09 |
Comparison: There was no formal hypothesis testing.90% CI: [-1.6, 1.8]ANCOVA
Secondary
Change From Baseline in Best Corrected Visual Acuity (BCVA) [Letters] After 24 Weeks
Absolute change from baseline in BCVA by Early Treatment Diabetic Retinopathy Study (ETDRS) letters after 24 weeks of treatment.
Time frame: Baseline and Week 24
Population: FAS\_US
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FYB201 | Change From Baseline in Best Corrected Visual Acuity (BCVA) [Letters] After 24 Weeks | 6.9 letters | Standard Deviation 10.12 |
| Lucentis | Change From Baseline in Best Corrected Visual Acuity (BCVA) [Letters] After 24 Weeks | 7.1 letters | Standard Deviation 10.42 |
| Total | Change From Baseline in Best Corrected Visual Acuity (BCVA) [Letters] After 24 Weeks | 7.0 letters | Standard Deviation 10.26 |
Comparison: There was no formal hypothesis testing.90% CI: [-1.6, 1.5]ANCOVA
Secondary
Change From Baseline in Best Corrected Visual Acuity (BCVA) [Letters] After 48 Weeks
Absolute change from baseline in BCVA by Early Treatment Diabetic Retinopathy Study (ETDRS) letters after 48 weeks of treatment.
Time frame: Baseline and Week 48
Population: FAS\_US
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FYB201 | Change From Baseline in Best Corrected Visual Acuity (BCVA) [Letters] After 48 Weeks | 7.8 letters | Standard Deviation 11.67 |
| Lucentis | Change From Baseline in Best Corrected Visual Acuity (BCVA) [Letters] After 48 Weeks | 8.0 letters | Standard Deviation 11.31 |
| Total | Change From Baseline in Best Corrected Visual Acuity (BCVA) [Letters] After 48 Weeks | 7.9 letters | Standard Deviation 11.48 |
Comparison: There was no formal hypothesis testing.90% CI: [-1.8, 1.7]ANCOVA
Secondary
Change in Foveal Central Subfield (FCS) Retinal Thickness From Baseline to Week 24
Absolute change in Foveal Central Subfield (FCS) retinal thickness \[µm\] from baseline to Week 24
Time frame: Baseline and Week 24
Population: FAS\_US
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FYB201 | Change in Foveal Central Subfield (FCS) Retinal Thickness From Baseline to Week 24 | -180.37 µm | Standard Deviation 128.522 |
| Lucentis | Change in Foveal Central Subfield (FCS) Retinal Thickness From Baseline to Week 24 | -181.63 µm | Standard Deviation 126.466 |
| Total | Change in Foveal Central Subfield (FCS) Retinal Thickness From Baseline to Week 24 | -181.02 µm | Standard Deviation 127.33 |
Comparison: There was no formal hypothesis testing.90% CI: [-22.62, 10.8]ANCOVA
Secondary
Change in Foveal Central Subfield (FCS) Retinal Thickness From Baseline to Week 48
Absolute change in Foveal Central Subfield (FCS) retinal thickness \[µm\] from baseline to Week 48
Time frame: Baseline and Week 48
Population: FAS\_US
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FYB201 | Change in Foveal Central Subfield (FCS) Retinal Thickness From Baseline to Week 48 | -182.85 µm | Standard Deviation 134.588 |
| Lucentis | Change in Foveal Central Subfield (FCS) Retinal Thickness From Baseline to Week 48 | -190.75 µm | Standard Deviation 128.691 |
| Total | Change in Foveal Central Subfield (FCS) Retinal Thickness From Baseline to Week 48 | -186.86 µm | Standard Deviation 131.532 |
Comparison: There was no formal hypothesis testing.90% CI: [-13.28, 20.63]ANCOVA
Secondary
Change in Foveal Centre Point (FCP) Retinal Thickness From Baseline to Week 24
Absolute change in Foveal Centre Point (FCP) retinal thickness \[µm\] from baseline to Week 24
Time frame: Baseline and Week 24
Population: FAS\_US
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FYB201 | Change in Foveal Centre Point (FCP) Retinal Thickness From Baseline to Week 24 | -203.94 µm | Standard Deviation 147.104 |
| Lucentis | Change in Foveal Centre Point (FCP) Retinal Thickness From Baseline to Week 24 | -205.45 µm | Standard Deviation 147.199 |
| Total | Change in Foveal Centre Point (FCP) Retinal Thickness From Baseline to Week 24 | -204.70 µm | Standard Deviation 146.986 |
Comparison: There was no formal hypothesis testing.90% CI: [-18.22, 19.6]ANCOVA
Secondary
Change in Foveal Centre Point (FCP) Retinal Thickness From Baseline to Week 48
Absolute change in Foveal Centre Point (FCP) retinal thickness \[µm\] from baseline to Week 48
Time frame: Baseline and Week 48
Population: FAS\_US
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FYB201 | Change in Foveal Centre Point (FCP) Retinal Thickness From Baseline to Week 48 | -213.26 µm | Standard Deviation 161.323 |
| Lucentis | Change in Foveal Centre Point (FCP) Retinal Thickness From Baseline to Week 48 | -211.02 µm | Standard Deviation 151.95 |
| Total | Change in Foveal Centre Point (FCP) Retinal Thickness From Baseline to Week 48 | -212.14 µm | Standard Deviation 156.521 |
Comparison: There was no formal hypothesis testing.90% CI: [-16.49, 21.85]ANCOVA
Secondary
Change in NEI VFQ-25 Composite Score From Baseline to Week 24
Absolute change from baseline to Week 24 in vision-related functioning and well-being measured by the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25) composite score. The NEI VFQ-25 is a 25 question quality of life questionnaire with possible item scores between 0 and 100. Higher scores represent better functioning. The composite score is calculated as average over all non-missing item scores.
Time frame: Baseline and Week 24
Population: FAS\_US
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FYB201 | Change in NEI VFQ-25 Composite Score From Baseline to Week 24 | 3.59 score on a scale | Standard Deviation 9.632 |
| Lucentis | Change in NEI VFQ-25 Composite Score From Baseline to Week 24 | 3.55 score on a scale | Standard Deviation 11.237 |
| Total | Change in NEI VFQ-25 Composite Score From Baseline to Week 24 | 3.57 score on a scale | Standard Deviation 10.457 |
Comparison: There was no formal hypothesis testing.90% CI: [-1.25, 1.67]ANCOVA
Secondary
Change in NEI VFQ-25 Composite Score From Baseline to Week 48
Absolute change from baseline to Week 48 in vision-related functioning and well-being measured by the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25) composite score. The NEI VFQ-25 is a 25 question quality of life questionnaire with possible item scores between 0 and 100. Higher scores represent better functioning. The composite score is calculated as average over all non-missing item scores.
Time frame: Baseline and Week 48
Population: FAS\_US
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FYB201 | Change in NEI VFQ-25 Composite Score From Baseline to Week 48 | 5.30 score on a scale | Standard Deviation 12.205 |
| Lucentis | Change in NEI VFQ-25 Composite Score From Baseline to Week 48 | 3.75 score on a scale | Standard Deviation 13.19 |
| Total | Change in NEI VFQ-25 Composite Score From Baseline to Week 48 | 4.53 score on a scale | Standard Deviation 12.714 |
Comparison: There was no formal hypothesis testing.90% CI: [0.04, 3.42]ANCOVA
Secondary
Change in Total Lesion Area From Baseline to Week 24
Absolute change in total lesion area \[mm²\] from baseline to Week 24
Time frame: Baseline and Week 24
Population: FAS\_US
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FYB201 | Change in Total Lesion Area From Baseline to Week 24 | -0.5742 mm² | Standard Deviation 4.79222 |
| Lucentis | Change in Total Lesion Area From Baseline to Week 24 | -0.7113 mm² | Standard Deviation 5.35854 |
| Total | Change in Total Lesion Area From Baseline to Week 24 | -0.6418 mm² | Standard Deviation 5.07361 |
Comparison: There was no formal hypothesis testing.90% CI: [-0.706, 0.846]ANCOVA
Secondary
Change in Total Lesion Area From Baseline to Week 48
Absolute change in total lesion area \[mm²\] from baseline to Week 48
Time frame: Baseline and Week 48
Population: FAS\_US
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FYB201 | Change in Total Lesion Area From Baseline to Week 48 | -0.6382 mm² | Standard Deviation 4.81194 |
| Lucentis | Change in Total Lesion Area From Baseline to Week 48 | -1.1814 mm² | Standard Deviation 5.4277 |
| Total | Change in Total Lesion Area From Baseline to Week 48 | -0.9123 mm² | Standard Deviation 5.13128 |
Comparison: There was no formal hypothesis testing.90% CI: [-0.547, 1.23]ANCOVA
Secondary
Fluid-free Macula at Each Visit
Number and percentage of patients with fluid-free macula at each visit
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
Population: FAS\_US
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| FYB201 | Fluid-free Macula at Each Visit | Week 12 | Fluid-free macula | 86 Participants |
| FYB201 | Fluid-free Macula at Each Visit | Baseline | Fluid-free macula | 0 Participants |
| FYB201 | Fluid-free Macula at Each Visit | Baseline | No fluid-free macula | 236 Participants |
| FYB201 | Fluid-free Macula at Each Visit | Week 4 | Fluid-free macula | 43 Participants |
| FYB201 | Fluid-free Macula at Each Visit | Week 4 | No fluid-free macula | 187 Participants |
| FYB201 | Fluid-free Macula at Each Visit | Week 8 | Fluid-free macula | 69 Participants |
| FYB201 | Fluid-free Macula at Each Visit | Week 8 | No fluid-free macula | 154 Participants |
| FYB201 | Fluid-free Macula at Each Visit | Week 12 | No fluid-free macula | 141 Participants |
| FYB201 | Fluid-free Macula at Each Visit | Week 16 | Fluid-free macula | 87 Participants |
| FYB201 | Fluid-free Macula at Each Visit | Week 16 | No fluid-free macula | 136 Participants |
| FYB201 | Fluid-free Macula at Each Visit | Week 20 | Fluid-free macula | 80 Participants |
| FYB201 | Fluid-free Macula at Each Visit | Week 20 | No fluid-free macula | 146 Participants |
| FYB201 | Fluid-free Macula at Each Visit | Week 24 | Fluid-free macula | 86 Participants |
| FYB201 | Fluid-free Macula at Each Visit | Week 24 | No fluid-free macula | 141 Participants |
| FYB201 | Fluid-free Macula at Each Visit | Week 28 | Fluid-free macula | 86 Participants |
| FYB201 | Fluid-free Macula at Each Visit | Week 28 | No fluid-free macula | 140 Participants |
| FYB201 | Fluid-free Macula at Each Visit | Week 32 | Fluid-free macula | 91 Participants |
| FYB201 | Fluid-free Macula at Each Visit | Week 32 | No fluid-free macula | 131 Participants |
| FYB201 | Fluid-free Macula at Each Visit | Week 36 | Fluid-free macula | 83 Participants |
| FYB201 | Fluid-free Macula at Each Visit | Week 36 | No fluid-free macula | 142 Participants |
| FYB201 | Fluid-free Macula at Each Visit | Week 40 | Fluid-free macula | 87 Participants |
| FYB201 | Fluid-free Macula at Each Visit | Week 40 | No fluid-free macula | 133 Participants |
| FYB201 | Fluid-free Macula at Each Visit | Week 44 | Fluid-free macula | 92 Participants |
| FYB201 | Fluid-free Macula at Each Visit | Week 44 | No fluid-free macula | 129 Participants |
| FYB201 | Fluid-free Macula at Each Visit | Week 48 | Fluid-free macula | 105 Participants |
| FYB201 | Fluid-free Macula at Each Visit | Week 48 | No fluid-free macula | 120 Participants |
| Lucentis | Fluid-free Macula at Each Visit | Week 16 | Fluid-free macula | 87 Participants |
| Lucentis | Fluid-free Macula at Each Visit | Week 40 | Fluid-free macula | 102 Participants |
| Lucentis | Fluid-free Macula at Each Visit | Week 16 | No fluid-free macula | 149 Participants |
| Lucentis | Fluid-free Macula at Each Visit | Week 20 | Fluid-free macula | 97 Participants |
| Lucentis | Fluid-free Macula at Each Visit | Week 48 | Fluid-free macula | 108 Participants |
| Lucentis | Fluid-free Macula at Each Visit | Week 20 | No fluid-free macula | 137 Participants |
| Lucentis | Fluid-free Macula at Each Visit | Week 40 | No fluid-free macula | 115 Participants |
| Lucentis | Fluid-free Macula at Each Visit | Week 24 | Fluid-free macula | 100 Participants |
| Lucentis | Fluid-free Macula at Each Visit | Week 24 | No fluid-free macula | 131 Participants |
| Lucentis | Fluid-free Macula at Each Visit | Week 28 | Fluid-free macula | 98 Participants |
| Lucentis | Fluid-free Macula at Each Visit | Week 44 | Fluid-free macula | 104 Participants |
| Lucentis | Fluid-free Macula at Each Visit | Week 28 | No fluid-free macula | 121 Participants |
| Lucentis | Fluid-free Macula at Each Visit | Week 32 | Fluid-free macula | 96 Participants |
| Lucentis | Fluid-free Macula at Each Visit | Week 32 | No fluid-free macula | 125 Participants |
| Lucentis | Fluid-free Macula at Each Visit | Baseline | Fluid-free macula | 2 Participants |
| Lucentis | Fluid-free Macula at Each Visit | Week 44 | No fluid-free macula | 116 Participants |
| Lucentis | Fluid-free Macula at Each Visit | Baseline | No fluid-free macula | 234 Participants |
| Lucentis | Fluid-free Macula at Each Visit | Week 36 | Fluid-free macula | 99 Participants |
| Lucentis | Fluid-free Macula at Each Visit | Week 4 | Fluid-free macula | 38 Participants |
| Lucentis | Fluid-free Macula at Each Visit | Week 4 | No fluid-free macula | 188 Participants |
| Lucentis | Fluid-free Macula at Each Visit | Week 8 | Fluid-free macula | 62 Participants |
| Lucentis | Fluid-free Macula at Each Visit | Week 36 | No fluid-free macula | 119 Participants |
| Lucentis | Fluid-free Macula at Each Visit | Week 8 | No fluid-free macula | 168 Participants |
| Lucentis | Fluid-free Macula at Each Visit | Week 12 | Fluid-free macula | 76 Participants |
| Lucentis | Fluid-free Macula at Each Visit | Week 12 | No fluid-free macula | 155 Participants |
| Lucentis | Fluid-free Macula at Each Visit | Week 48 | No fluid-free macula | 113 Participants |
| Total | Fluid-free Macula at Each Visit | Week 12 | Fluid-free macula | 162 Participants |
| Total | Fluid-free Macula at Each Visit | Week 32 | No fluid-free macula | 256 Participants |
| Total | Fluid-free Macula at Each Visit | Week 8 | Fluid-free macula | 131 Participants |
| Total | Fluid-free Macula at Each Visit | Week 16 | No fluid-free macula | 285 Participants |
| Total | Fluid-free Macula at Each Visit | Week 40 | Fluid-free macula | 189 Participants |
| Total | Fluid-free Macula at Each Visit | Baseline | Fluid-free macula | 2 Participants |
| Total | Fluid-free Macula at Each Visit | Week 20 | Fluid-free macula | 177 Participants |
| Total | Fluid-free Macula at Each Visit | Week 36 | No fluid-free macula | 261 Participants |
| Total | Fluid-free Macula at Each Visit | Week 16 | Fluid-free macula | 174 Participants |
| Total | Fluid-free Macula at Each Visit | Week 20 | No fluid-free macula | 283 Participants |
| Total | Fluid-free Macula at Each Visit | Baseline | No fluid-free macula | 470 Participants |
| Total | Fluid-free Macula at Each Visit | Week 8 | No fluid-free macula | 322 Participants |
| Total | Fluid-free Macula at Each Visit | Week 24 | Fluid-free macula | 186 Participants |
| Total | Fluid-free Macula at Each Visit | Week 40 | No fluid-free macula | 248 Participants |
| Total | Fluid-free Macula at Each Visit | Week 4 | Fluid-free macula | 81 Participants |
| Total | Fluid-free Macula at Each Visit | Week 24 | No fluid-free macula | 272 Participants |
| Total | Fluid-free Macula at Each Visit | Week 48 | Fluid-free macula | 213 Participants |
| Total | Fluid-free Macula at Each Visit | Week 36 | Fluid-free macula | 182 Participants |
| Total | Fluid-free Macula at Each Visit | Week 28 | Fluid-free macula | 184 Participants |
| Total | Fluid-free Macula at Each Visit | Week 12 | No fluid-free macula | 296 Participants |
| Total | Fluid-free Macula at Each Visit | Week 4 | No fluid-free macula | 375 Participants |
| Total | Fluid-free Macula at Each Visit | Week 28 | No fluid-free macula | 261 Participants |
| Total | Fluid-free Macula at Each Visit | Week 44 | Fluid-free macula | 196 Participants |
| Total | Fluid-free Macula at Each Visit | Week 44 | No fluid-free macula | 245 Participants |
| Total | Fluid-free Macula at Each Visit | Week 32 | Fluid-free macula | 187 Participants |
| Total | Fluid-free Macula at Each Visit | Week 48 | No fluid-free macula | 233 Participants |