Efficacy and Safety of the Biosimilar Ranibizumab FYB201 in Comparison to Lucentis in Patients With Neovascular Age-related Macular Degeneration

Study Overview
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Brief Summary
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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.

Official Title
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Efficacy and Safety of the Biosimilar Ranibizumab FYB201 in Comparison to Lucentis in Patients With Neovascular Age-related Macular Degeneration

Conditions
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Age-related Macular Degeneration (AMD)

Intervention / Treatment
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* Biological: ranibizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FYB201<br>FYB201 is provided as single use vials and will be administered by intra-vitreal injection. | Biological: ranibizumab<br> <br> |
| Active Comparator: Lucentis<br>Lucentis® is provided as single use vials and will be administered by intra-vitreal injection. | Biological: ranibizumab<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and Week 24 | 
| 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. | Baseline and Week 48 | 
| 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. | Baseline and 12 Months | 
| 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 | Baseline and Week 24 | 
| 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 | Baseline and Week 48 | 
| 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 | Baseline and Week 24 | 
| 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 | Baseline and Week 48 | 
| Change in Total Lesion Area From Baseline to Week 24 | Absolute change in total lesion area [mm²] from baseline to Week 24 | Baseline and Week 24 | 
| Change in Total Lesion Area From Baseline to Week 48 | Absolute change in total lesion area [mm²] from baseline to Week 48 | Baseline and Week 48 | 
| 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. | Baseline and Week 24 | 
| 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. | Baseline and Week 48 | 
| Active CNV Leakage at Week 24 | Number and percentage of patients with active CNV leakage at Week 24 | Baseline and Week 24 | 
| Active CNV Leakage at Week 48 | Number and percentage of patients with active CNV leakage at Week 48 | Baseline and Week 48 | 
| Fluid-free Macula at Each Visit | Number and percentage of patients with fluid-free macula at each visit | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 | 
| Anti-drug Antibodies by Scheduled eCRF Visit | Frequency of patients with anti-drug antibodies (ADAs) by scheduled eCRF visit | Baseline and Weeks 1, 4, 12, 24, 48 | 
| 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). | Baseline and up to Week 48 |