Comparing the Efficacy and Safety of Biosimilar Candidate Xlucane Versus Lucentis® in Patients With nAMD

NCT ID: NCT03805100

Last Updated: 2023-11-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 582 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-19
• Study Completion Date: 2021-11-11

Brief Summary

The objectives of the study are to demonstrate the equivalence of Xlucane to Lucentis® in treatment of subjects with wet (ie, neovascular) age-related macular degeneration (wAMD).

Detailed Description

This is a phase III multicenter, double-masked, randomized, parallel group study in subjects with wAMD. Approximately 580 subjects will be enrolled and randomized in a 1:1 ratio to receive either Lucentis® or the investigational product, Xlucane in the study eye once every 4 weeks for 52 weeks. The study eye will be defined as the eye meeting the enrollment criteria. The assigned study drug will be administered as an ophthalmic intravitreal (IVT) injection. A subgroup of 60 subjects at a select number of participating sites will be sequentially asked to participate in an evaluation of PK.

Conditions

Macular Degeneration

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Xlucane

Xlucane (0.05 mL of 10 mg/mL ranibizumab) in the study eye monthly for 52 weeks.

Group Type: EXPERIMENTAL

Ranibizumab

Intervention Type: BIOLOGICAL

Intravitreal injection

Lucentis

Lucentis (0.05 mL of 10 mg/mL ranibizumab) in the study eye monthly for 52 weeks.

Group Type: ACTIVE_COMPARATOR

Ranibizumab

Intervention Type: BIOLOGICAL

Intravitreal injection

Interventions

Ranibizumab

Intravitreal injection

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Written and signed informed consent form obtained at screening, before any study-related procedures.
• Willingness and ability to undertake all scheduled visits and assessments as judged by the investigator.
• Newly diagnosed, active subfoveal Choroidal Neovascularization (CNV) lesion secondary to age-related macular degeneration (AMD) in the study eye. Note: Active CNV indicates the presence of leakage as evidenced by Fluorescein Angiography (FA) and intra- or subretinal fluid as evidenced by Optical Coherence Tomography (OCT) which must be confirmed by the central reading center during Screening:

1. The area of CNV must be ≥ 50% of the total lesion area in the study eye, and

2. Total lesion area ≤ 9.0 Disc Areas (DA) in size (including blood, scars and neovascularization) as assessed by FA in the study eye.

• Best Corrected Visual Acuity (BCVA) of ≤ 73 and ≥ 49 ETDRS letter score in the study eye, using ETDRS chart (20/40 to 20/100 Snellen equivalent) at Screening.
• Fellow eye should not be expected to need any anti-VEGF treatment for the duration of study participation.
• Age ≥ 50 years at screening.
• Male and female subjects of childbearing potential must be willing to completely abstain or agree to use an appropriate method of contraception, from the time of signing informed consent and for the duration of study participation through 3 months, following the last dose of study drug.

Exclusion Criteria

• Any previous intervention including pharmacological treatment, laser and/or surgery for wAMD in either eye; (Exception: Vitamin supplementation for AMD prevention).
• Any previous vitreoretinal surgery in the study eye for any cause.
• Any previous IVT treatment including any anti-VEGF medications, steroids and/or any other investigational medication in either eye.
• The use of long-acting steroids, either systemic or intraocular in any eye, in the 18 months before planned initiation of study treatment. (Note: Iluvien® [fluocinolone acetonide intravitreal], current or planned implantation during the study, is prohibited.)
• Subfoveal fibrosis, atrophy or scarring extending > 50% of total lesion area, in the study eye as assessed by the investigator at screening and confirmed by the central reading center prior to randomization.
• Choroidal neovascularization in either eye due to non-AMD causes (eg, DME, RVO, ocular histoplasmosis or trauma, etc.) as assessed by FA and confirmed by central reading center.
• Active or recent (within 28 days prior to randomization) intraocular, extraocular, and periocular inflammation or infection in either eye.
• History of idiopathic or autoimmune-associated uveitis in either eye.
• Infectious conjunctivitis, keratitis, scleritis or endophthalmitis in either eye.
• Unmedicated intraocular pressure (IOP) ≥ 30 mmHg at Screening in either eye.
• Topical ocular corticosteroids administered for ≥ 30 consecutive days in the study eye within 90 days prior to Screening.
• Spherical equivalent of the refractive error in the study eye demonstrating more than 8 diopters of myopia.
• Corneal transplant or corneal dystrophy in the study eye.
• History of rhegmatogenous retinal detachment in the study eye.
• History of macular hole in the study eye.
• Retinal pigment epithelial tear or rip, involving the macula in the study eye as assessed by FA and confirmed by the central reading center.
• Current vitreous hemorrhage in the study eye.
• Subretinal hemorrhage that is ≥ 50% of the total lesion area in the study eye, or if the subretinal hemorrhage involves the fovea is 1 or more DA (≥ 2.54 mm2) in size in the study eye, as assessed by FA and confirmed by the central reading center.
• Other intraocular surgery (including cataract surgery) in the study eye within the 3 months prior to baseline. The yttrium aluminum garnet [YAG] posterior capsulotomy is allowed not later than 4 weeks prior to screening.
• Any concurrent intraocular condition in the study eye (eg, cataract or diabetic retinopathy) that, in the opinion of the investigator, could require treatment during the study period to prevent or treat loss of visual acuity.
• Significant media opacities (including cataract) in the study eye interfering with BCVA assessment or fundus imaging (FA/FP/OCT).
• Aphakia or absence of the posterior capsule in the study eye, unless it occurred as a result of a YAG posterior capsulotomy in association with prior posterior chamber intraocular lens implantation.
• Presence of advanced glaucoma or optic neuropathy that involve(s) or threaten(s) the central visual field in the study eye (as judged by the investigator).
• History of glaucoma filtering surgery or argon laser trabeculoplasty in the study eye (Exception: Laser iridotomy and selective laser trabeculoplasty are allowed).
• Uncontrolled ocular glaucoma or hypertension in the study eye, defined as IOP ≥ 25 mmHg despite treatment with anti-glaucoma medication.
• Any previous systemic anti-VEGF treatment (eg, bevacizumab).
• Contraindication for Lucentis® (hypersensitivity to ranibizumab or to any of the study treatment excipients).
• Current treatment for active systemic infection.
• Females who are pregnant, nursing, planning a pregnancy during the study, or of childbearing potential and not using a reliable method of contraception and/or not willing to use a reliable method of contraception during their participation in the study.
• Participation in another clinical trial within the previous 3 months or any other clinical trial of anti-angiogenic drugs.
• Reasonable suspicion of other disease or condition that might render the subject at a high risk of treatment complications or otherwise confound interpretation of the study results (as judged by the investigator).
• PK subgroup only: Contraindication for additional blood sampling (as judged by the investigator).

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stada Arzneimittel AG

INDUSTRY

Sponsor Role: collaborator

Xbrane Biopharma AB

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anat Loewenstein, Professor

Role: PRINCIPAL_INVESTIGATOR

Tel-Aviv Sourasky Medical Center

Locations

Retinal Research Institute, LLC

Gilbert, Arizona, United States

Arizona Retina and Vitreous Consultants

Phoenix, Arizona, United States

Retina Centers P.C

Tucson, Arizona, United States

Win Retina

Arcadia, California, United States

The Retina Partners

Encino, California, United States

Mark B. Kislinger MD Inc.

Glendora, California, United States

Retina Consultants Medical Group Inc.

Sacramento, California, United States

Colorado Retina Associates

Golden, Colorado, United States

Fort Lauderdale Eye Institute

Fort Lauderdale, Florida, United States

Sarasota Retina Institute

Sarasota, Florida, United States

Center for Retina and Macular Disease

Winter Haven, Florida, United States

Southeast Retina Center

Augusta, Georgia, United States

Georgia Retina

Marietta, Georgia, United States

Gailey Eye Clinic

Bloomington, Illinois, United States

Sabates Eye Centers

Leawood, Kansas, United States

Retina Vitreous Surgeons of Central New York PC

New York, New York, United States

Retina Associates of Western New York

Rochester, New York, United States

Charleston Neuroscience Institute

Ladson, South Carolina, United States

Black Hills Regional Eye Institute

Rapid City, South Dakota, United States

Retina Research Institute of Texas

Abilene, Texas, United States

Austin Retina Associates

Austin, Texas, United States

Houston Eye Associates

Houston, Texas, United States

Retina Consultants of Houston

Houston, Texas, United States

Medical Center Ophthalmology Associates

San Antonio, Texas, United States

Retina Consultants of Houston

The Woodlands, Texas, United States

Strategic Clinical Research Group LLC

Willow Park, Texas, United States

Specialized Eye hospital for active treatment Luxor

Plovdiv, , Bulgaria

Specialized eye clinic Zrenie

Sofia, , Bulgaria

Specialized Eye hospital for active treatment Acad. Pashev

Sofia, , Bulgaria

Specialized Hospital for Active Treatment of Eye Diseases "Zora"

Sofia, , Bulgaria

AMCSMP Eye Clinic St. Petka

Varna, , Bulgaria

Všeobecná FN v Praze

Brno, , Czechia

Oční klinika, Fakultní nemocnice

Hradec Králové, , Czechia

Faculty Hospital Kralovske Vinohrady

Prague, , Czechia

VFN Ocni klinika

Prague, , Czechia

Axon-Clinical, s.r.o.

Prague, , Czechia

OÜ Dr Kai Noor Silmakabinet

Tallinn, , Estonia

Mustame Eye Centre

Tallinn, , Estonia

Magyar Honvédség Egészségügyi Központ

Budapest, , Hungary

Department of Ophthalmology, Semmelweis University

Budapest, , Hungary

Bajcsy-Zsilinszky Hospital

Budapest, , Hungary

Szent Imre Teaching Hospital

Budapest, , Hungary

Budapest Retina Associates

Budapest, , Hungary

Jahn Ferenc South-Budapest Hospital

Budapest, , Hungary

University of Debrecen

Debrecen, , Hungary

Szabolcs-Szatmr-Bereg County Hospital

Nyíregyháza, , Hungary

Ganglion Medical Center

Pécs, , Hungary

Markusovszky University Teaching Hospital

Szombathely, , Hungary

Zalan Megyei Szent Rafael kórház

Zalaegerszeg, , Hungary

Rising Retina Clinic

Ahmedabad, , India

Soroka University Medical Center

Beersheba, , Israel

Bnai Zion Medical Center

Haifa, , Israel

Rambam Health Care Campus

Haifa, , Israel

Carmel Medical Center

Haifa, , Israel

Shaare Zedek Medical Center

Jerusalem, , Israel

Hadassah University Hospital

Jerusalem, , Israel

Meir Medical Center

Kfar Saba, , Israel

Rabin Medical Center

Petah Tikva, , Israel

Kaplan Medical Center

Rehovot, , Israel

The Tel Aviv Sourasky Medical Centre

Tel Aviv, , Israel

Asaf Harofe Hospital

Zrifin, , Israel

P.Stradins University Hospital

Riga, , Latvia

The Dr Solomatin Eye Center

Riga, , Latvia

Hospital of Lithuanian University of Health Sciences Kauno klinikos

Kaunas, , Lithuania

Vilnius University Hospital Santaros Klinikos

Vilnius, , Lithuania

Klinika Okulistyczna Oftalmika

Bydgoszcz, , Poland

Professor K. Gibinski University Clinical Centre

Katowice, , Poland

Samodzielny Publiczny Szpital Kliniczny Nr 1 w Lublinie

Lublin, , Poland

Centrum Diagnostyki i Mikrochirurgii Oka LENS

Olsztyn, , Poland

Dr Nowosielska Okulistyka i Chirurgia Oka

Warsaw, , Poland

Retina Okulistyka Sp. z o.o. sp. km

Warsaw, , Poland

Clinica Retina

Bucharest, , Romania

Opticlass Timisoara

Timișoara, , Romania

FGAU NMRC MNTK Eye Microsurgery n.a. acad. S.N. Fyodorov Cheboksary Branch

Cheboksary, , Russia

LLC Kuzlyar

Kazan', , Russia

Federal State Budget Scientific Institute of Eye Diseases

Moscow, , Russia

S. Fyodorov Eye Microsurgery Federal State Institution

Moscow, , Russia

S.Fyodorov Eye Microsurgery Federal State Institution

Saint Petersburg, , Russia

First Pavlov State Medical University of St.Petersburg

Saint Petersburg, , Russia

F.D.Roosevelt Hospital

Banská Bystrica, , Slovakia

Univerzitna nemocnica Bratislava, Nemocnica Ruzinov

Bratislava, , Slovakia

Fakultna nemocnica Trencin

Trenčín, , Slovakia

Fakultna nemocnica s poliklinikou Zilina

Žilina, , Slovakia

Hospital General Universitario de Albacete

Albacete, , Spain

Instituto de Microcirugia Ocular

Barcelona, , Spain

Hospital de Viladecans

Barcelona, , Spain

Bellvitge University Hospital

L'Hospitalet de Llobregat, , Spain

Hospital Universitario Puerta de Hierro-Majadahonda

Madrid, , Spain

Hospital Clinico San Carlos

Madrid, , Spain

Clinica Universidad de Navarr

Pamplona, , Spain

Hospital General de Catalunya

Sant Cugat del Vallès, , Spain

Hospital Universitario Virgen Macarena

Seville, , Spain

Unit of Macula. Oftalvist Clinic

Valencia, , Spain

FISABIO-Oftalmologia Medica FOM

Valencia, , Spain

Hospital Universitario Rio Hortega

Valladolid, , Spain

Hospital Clinico Universitario Lozano Blesa

Zaragoza, , Spain

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Regional Clinical Hospital Center for Emergency Medical Care And Disaster Medicine

Kharkiv, , Ukraine

Medical and Diagnostic Centre PE PMC "Acinus"

Kropyvnytskyi, , Ukraine

Filatov Institute of Eye Diseases Tissue Therapy

Odesa, , Ukraine

Clinic of Professor Serhiienko

Vinnitsa, , Ukraine

Medical center LTD VISUS

Zaporizhzhia, , Ukraine

Countries

United States; Bulgaria; Czechia; Estonia; Hungary; India; Israel; Latvia; Lithuania; Poland; Romania; Russia; Slovakia; Spain; Ukraine

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

XBR1001

Identifier Type: -

Identifier Source: org_study_id