Clinical trial NCT02611778: Efficacy and Safety of the Biosimilar Ranibizumab FYB201 in Comparison to Lucentis in Patients With Neovascular Age-related Macular Degeneration
Official title: Efficacy and Safety of the Biosimilar Ranibizumab FYB201 in Comparison to Lucentis in Patients With Neovascular Age-related Macular Degeneration
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Age-related Macular Degeneration (AMD)
Lead sponsor: Bioeq GmbH
Sponsor class: INDUSTRY
First posted: 2015-11-23
Enrollment: 712
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in Best Corrected Visual Acuity (BCVA) [Letters] After 8 Weeks
timeFrame: Baseline and Week 8
Secondary outcomes:
measure: Change From Baseline in Best Corrected Visual Acuity (BCVA) [Letters] After 24 Weeks
timeFrame: Baseline and Week 24
measure: Change From Baseline in Best Corrected Visual Acuity (BCVA) [Letters] After 48 Weeks
timeFrame: Baseline and Week 48
measure: Change From Baseline in Best Corrected Visual Acuity (BCVA) [Letters] After 12 Months
timeFrame: Baseline and 12 Months
measure: Change in Foveal Centre Point (FCP) Retinal Thickness From Baseline to Week 24
timeFrame: Baseline and Week 24
measure: Change in Foveal Centre Point (FCP) Retinal Thickness From Baseline to Week 48
timeFrame: Baseline and Week 48
measure: Change in Foveal Central Subfield (FCS) Retinal Thickness From Baseline to Week 24
timeFrame: Baseline and Week 24
measure: Change in Foveal Central Subfield (FCS) Retinal Thickness From Baseline to Week 48
timeFrame: Baseline and Week 48
measure: Change in Total Lesion Area From Baseline to Week 24
timeFrame: Baseline and Week 24
measure: Change in Total Lesion Area From Baseline to Week 48
timeFrame: Baseline and Week 48
measure: Change in NEI VFQ-25 Composite Score From Baseline to Week 24
timeFrame: Baseline and Week 24
measure: Change in NEI VFQ-25 Composite Score From Baseline to Week 48
timeFrame: Baseline and Week 48
measure: Active CNV Leakage at Week 24
timeFrame: Baseline and Week 24
measure: Active CNV Leakage at Week 48
timeFrame: Baseline and Week 48
measure: Fluid-free Macula at Each Visit
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
measure: Anti-drug Antibodies by Scheduled eCRF Visit
timeFrame: Baseline and Weeks 1, 4, 12, 24, 48
measure: Anti-drug Antibodies Pre- and Post-first Dosing
timeFrame: Baseline and up to Week 48
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Research Site
city: Brno
country: Czechia
facility: Research Site
city: Ostrava
country: Czechia
facility: Research Site
city: Plzen
country: Czechia
facility: Research Site
city: Praha
country: Czechia
facility: Research Site
city: Zlín
country: Czechia
facility: Research Site
city: Dijon
country: France
facility: Research Site
city: Lyon
country: France
facility: Research Site
city: Nantes
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Bonn
country: Germany
facility: University of Bonn, Department of Ophthalmology
city: Dresden
country: Germany
facility: Research Site
city: Freiburg
country: Germany
facility: Research Site
city: Göttingen
country: Germany
facility: Research Site
city: Hannover
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Mainz
country: Germany
facility: Research Site
city: Tuebingen
country: Germany
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Debrecen
country: Hungary
facility: Research Site
city: Nyíregyháza
country: Hungary
facility: Research Site
city: Pécs
country: Hungary
facility: Research Site
city: Szeged
country: Hungary
facility: Research Site
city: Zalaegerszeg
country: Hungary
facility: Research Site
city: Be'er Sheva
country: Israel
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Kfar Saba
country: Israel
facility: Research Site
city: Petach Tikva
country: Israel
facility: Research Site
city: Ramat Gan
country: Israel
facility: Research Site
city: Reẖovot
country: Israel
facility: Research Site
city: Tel Aviv
country: Israel
facility: Research Site
city: Zrifin
country: Israel
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
city: Chieti
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Pisa
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Torino
country: Italy
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Rzeszów
country: Poland
facility: Research Site
city: Tarnowskie Góry
country: Poland
facility: Research Site
city: Tarnów
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Łódź
country: Poland
facility: Research Site
city: Kazan
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Zaragoza
country: Spain
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Odesa
country: Ukraine
facility: Research Site
city: Bradford
country: United Kingdom
facility: Research Site
city: Bristol
country: United Kingdom
facility: Research Site
city: Camberley
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Rugby
country: United Kingdom
facility: Research Site
Study officials:
affiliation: University of Bonn, Department of Ophthalmology
name: Frank G. Holz, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: