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

Age-related Macular Degeneration (AMD) Clinical Trial

— COLUMBUS-AMD  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02611778
• Other study ID #: FYB201-C2015-01-P3
• Status: Completed
• Phase: Phase 3
• Start date: December 19, 2015
• Est. completion date: June 6, 2018

Study information

• Verified date: September 2021
• Source: Bioeq GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 712
• Est. completion date: June 6, 2018
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Age-related Macular Degeneration (AMD)
• Macular Degeneration

Intervention

Biological:
• ranibizumab

Locations

Country	Name	City	State
Austria	Research Site	Vienna
Czechia	Research Site	Brno
Czechia	Research Site	Ostrava
Czechia	Research Site	Plzen
Czechia	Research Site	Praha
Czechia	Research Site	Zlín
France	Research Site	Dijon
France	Research Site	Lyon
France	Research Site	Nantes
France	Research Site	Paris
Germany	University of Bonn, Department of Ophthalmology	Bonn
Germany	Research Site	Dresden
Germany	Research Site	Freiburg
Germany	Research Site	Göttingen
Germany	Research Site	Hannover
Germany	Research Site	Leipzig
Germany	Research Site	Mainz
Germany	Research Site	Tuebingen
Hungary	Research Site	Budapest
Hungary	Research Site	Debrecen
Hungary	Research Site	Nyíregyháza
Hungary	Research Site	Pécs
Hungary	Research Site	Szeged
Hungary	Research Site	Zalaegerszeg
Israel	Research Site	Be'er Sheva
Israel	Research Site	Haifa
Israel	Research Site	Jerusalem
Israel	Research Site	Kfar Saba
Israel	Research Site	Petach Tikva
Israel	Research Site	Ramat Gan
Israel	Research Site	Re?ovot
Israel	Research Site	Tel Aviv
Israel	Research Site	Zrifin
Italy	Research Site	Bologna
Italy	Research Site	Chieti
Italy	Research Site	Milano
Italy	Research Site	Pisa
Italy	Research Site	Roma
Italy	Research Site	Torino
Poland	Research Site	Bydgoszcz
Poland	Research Site	Lódz
Poland	Research Site	Rzeszów
Poland	Research Site	Tarnów
Poland	Research Site	Tarnowskie Góry
Poland	Research Site	Warszawa
Russian Federation	Research Site	Kazan
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Saint Petersburg
Spain	Research Site	Barcelona
Spain	Research Site	Valencia
Spain	Research Site	Zaragoza
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Odesa
United Kingdom	Research Site	Bradford
United Kingdom	Research Site	Bristol
United Kingdom	Research Site	Camberley
United Kingdom	Research Site	London
United Kingdom	Research Site	Rugby

Sponsors (1)

Lead Sponsor	Collaborator
Bioeq GmbH

Countries where clinical trial is conducted

Austria,  Czechia,  France,  Germany,  Hungary,  Israel,  Italy,  Poland,  Russian Federation,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Baseline and Week 8
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.	Baseline and Week 24
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.	Baseline and Week 48
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.	Baseline and 12 Months
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	Baseline and Week 24
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	Baseline and Week 48
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	Baseline and Week 24
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	Baseline and Week 48
Secondary	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
Secondary	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
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.	Baseline and Week 24
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.	Baseline and Week 48
Secondary	Active CNV Leakage at Week 24	Number and percentage of patients with active CNV leakage at Week 24	Baseline and Week 24
Secondary	Active CNV Leakage at Week 48	Number and percentage of patients with active CNV leakage at Week 48	Baseline and Week 48
Secondary	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
Secondary	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
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).	Baseline and up to Week 48