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

A Phase III Double-Blind, Parallel Group, Multicenter Study to Compare the Efficacy and Safety of Xlucane Versus Lucentis® in Patients With Neovascular Age-Related Macular Degeneration

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).

Study Overview

• Status: Completed
• Conditions: Macular Degeneration
• Intervention / Treatment: Biological: Ranibizumab

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.

• Study Type: Interventional
• Enrollment (Actual): 582
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Plovdiv, Bulgaria, 4000
    • Specialized Eye hospital for active treatment Luxor
  • Sofia, Bulgaria, 1408
    • Specialized eye clinic Zrenie
  • Sofia, Bulgaria, 1517
    • Specialized Eye hospital for active treatment Acad. Pashev
  • Sofia, Bulgaria, 1744
    • Specialized Hospital for Active Treatment of Eye Diseases "Zora"
  • Varna, Bulgaria, 9010
    • AMCSMP Eye Clinic St. Petka
• Czechia
  • Brno, Czechia, 625 00
    • Všeobecná FN v Praze
  • Hradec Králové, Czechia, 50005
    • Oční klinika, Fakultní nemocnice
  • Praha, Czechia, 10034
    • Faculty Hospital Královské Vinohrady
  • Praha, Czechia, 12808
    • VFN Ocni klinika
  • Praha, Czechia, 15000
    • Axon-Clinical, s.r.o.
• Estonia
  • Tallin, Estonia, 11412
    • OÜ Dr Kai Noor Silmakabinet
  • Tallinn, Estonia, 13419
    • Mustame Eye Centre
• Hungary
  • Budapest, Hungary, 1062
    • Magyar Honvédség Egészségügyi Központ
  • Budapest, Hungary, 1085
    • Department of Ophthalmology, Semmelweis University
  • Budapest, Hungary, 1106
    • Bajcsy-Zsilinszky Hospital
  • Budapest, Hungary, 1133
    • Budapest Retina Associates
  • Budapest, Hungary, 1115
    • Szent Imre Teaching Hospital
  • Budapest, Hungary, 1204
    • Jahn Ferenc South-Budapest Hospital
  • Debrecen, Hungary, 4032
    • University of Debrecen
  • Nyíregyháza, Hungary, 4400
    • Szabolcs-Szatmr-Bereg County Hospital
  • Pécs, Hungary, 7621
    • Ganglion Medical Center
  • Szombathely, Hungary, 9700
    • Markusovszky University Teaching Hospital
  • Zalaegerszeg, Hungary, 8900
    • Zalan Megyei Szent Rafael kórház
• India
  • Ahmedabad, India, 380015
    • Rising Retina Clinic
• Israel
  • Beer Sheva, Israel, 84101
    • Soroka University Medical Center
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus
  • Haifa, Israel, 31048
    • Bnai Zion Medical Center
  • Haifa, Israel, 3436212
    • Carmel Medical Center
  • Jerusalem, Israel, 9103102
    • Shaare Zedek Medical Center
  • Jerusalem, Israel, 9112001
    • Hadassah University Hospital
  • Kfar Saba, Israel, 4428164
    • Meir Medical Center
  • Petah Tikva, Israel, 49100
    • Rabin Medical Center
  • Reẖovot, Israel, 7610001
    • Kaplan Medical Center
  • Tel Aviv, Israel, 64239
    • The Tel Aviv Sourasky Medical Centre
  • Zrifin, Israel, 73000
    • Asaf Harofe Hospital
• Latvia
  • Riga, Latvia, 1002
    • P.Stradins University Hospital
  • Riga, Latvia, 1050
    • The Dr Solomatin Eye Center
• Lithuania
  • Kaunas, Lithuania, 50161
    • Hospital of Lithuanian University of Health Sciences Kauno Klinikos
  • Vilnius, Lithuania, 08661
    • Vilnius University Hospital Santaros Klinikos
• Poland
  • Bydgoszcz, Poland, 85631
    • Klinika Okulistyczna OFTALMIKA
  • Katowice, Poland, 40514
    • Professor K. Gibinski University Clinical Centre
  • Lublin, Poland, 20079
    • Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
  • Olsztyn, Poland, 10424
    • Centrum Diagnostyki i Mikrochirurgii Oka LENS
  • Warszawa, Poland, 01249
    • Dr Nowosielska Okulistyka i Chirurgia Oka
  • Warszawa, Poland, 01364
    • Retina Okulistyka Sp. z o.o. sp. km
• Romania
  • Bucharest, Romania, 014142
    • Clinica Retina
  • Timişoara, Romania, 300012
    • Opticlass Timisoara
• Russian Federation
  • Cheboksary, Russian Federation, 428028
    • FGAU NMRC MNTK Eye Microsurgery n.a. acad. S.N. Fyodorov Cheboksary Branch
  • Kazan, Russian Federation, 420066
    • LLC Kuzlyar
  • Moscow, Russian Federation, 119021
    • Federal State Budget Scientific Institute of Eye Diseases
  • Moscow, Russian Federation, 127486
    • S. Fyodorov Eye Microsurgery Federal State Institution
  • Saint Petersburg, Russian Federation, 192283
    • S.Fyodorov Eye Microsurgery Federal State Institution
  • Saint Petersburg, Russian Federation, 197022
    • First Pavlov State Medical University of St.Petersburg
• Slovakia
  • Banská Bystrica, Slovakia, 97517
    • F.D.Roosevelt Hospital
  • Bratislava, Slovakia, 82606
    • Univerzitna nemocnica Bratislava, Nemocnica Ruzinov
  • Trenčín, Slovakia, 91171
    • Fakultna nemocnica Trencin
  • Žilina, Slovakia, 1207
    • Fakultna nemocnica s poliklinikou Zilina
• Spain
  • Albacete, Spain, 2006
    • Hospital General Universitario de Albacete
  • Barcelona, Spain, 8035
    • Instituto de Microcirugia Ocular
  • Barcelona, Spain, 8840
    • Hospital de Viladecans
  • L'Hospitalet De Llobregat, Spain, 8907
    • Bellvitge University Hospital
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 02008
    • Hospital Universitario Puerta de Hierro-Majadahonda
  • Pamplona, Spain, 31008
    • Clinica Universidad de Navarr
  • Sant Cugat Del Vallès, Spain, 08195
    • Hospital General de Catalunya
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Valencia, Spain, 46004
    • Unit of Macula. Oftalvist Clinic
  • Valencia, Spain, 46015
    • FISABIO-Oftalmologia Medica FOM
  • Valladolid, Spain, 47012
    • Hospital Universitario Río Hortega
  • Zaragoza, Spain, 50009
    • Hospital Clínico Universitario Lozano Blesa
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
• Ukraine
  • Kharkiv, Ukraine, 61204
    • Regional Clinical Hospital Center for Emergency Medical Care and Disaster Medicine
  • Kropyvnytskyi, Ukraine, 25006
    • Medical and Diagnostic Centre PE PMC "Acinus"
  • Odessa, Ukraine, 65061
    • Filatov Institute of Eye Diseases Tissue Therapy
  • Vinnitsa, Ukraine, 21000
    • Clinic of Professor Serhiienko
  • Zaporizhzhia, Ukraine, 69032
    • Medical center LTD VISUS
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85296
      • Retinal Research Institute, LLC
    • Phoenix, Arizona, United States, 85021-8880
      • Arizona Retina and Vitreous Consultants
    • Tucson, Arizona, United States, 85704-5611
      • Retina Centers P.C
  • California
    • Arcadia, California, United States, 91006-3607
      • Win Retina
    • Encino, California, United States, 91436-2018
      • The Retina Partners
    • Glendora, California, United States, 91741
      • Mark B. Kislinger MD Inc.
    • Sacramento, California, United States, 95819
      • Retina Consultants Medical Group Inc.
  • Colorado
    • Golden, Colorado, United States, 80401-5069
      • Colorado Retina Associates
  • Florida
    • Fort Lauderdale, Florida, United States, 33324-3118
      • Fort Lauderdale Eye Institute
    • Sarasota, Florida, United States, 34239-7246
      • Sarasota Retina Institute
    • Winter Haven, Florida, United States, 33880-3919
      • Center for Retina and Macular Disease
  • Georgia
    • Augusta, Georgia, United States, 30909-6440
      • Southeast Retina Center
    • Marietta, Georgia, United States, 30060
      • Georgia Retina
  • Illinois
    • Bloomington, Illinois, United States, 61704
      • Gailey Eye Clinic
  • Kansas
    • Leawood, Kansas, United States, 66211
      • Sabates Eye Centers
  • New York
    • New York, New York, United States, 13224
      • Retina Vitreous Surgeons of Central New York PC
    • Rochester, New York, United States, 14620-4655
      • Retina Associates of Western New York
  • South Carolina
    • Ladson, South Carolina, United States, 29456
      • Charleston Neuroscience Institute
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Black Hills Regional Eye Institute
  • Texas
    • Abilene, Texas, United States, 79606
      • Retina Research Institute of Texas
    • Austin, Texas, United States, 78705-1169
      • Austin Retina Associates
    • Houston, Texas, United States, 77025-1756
      • Houston Eye Associates
    • Houston, Texas, United States, 77030-2727
      • Retina Consultants of Houston
    • San Antonio, Texas, United States, 78240-1502
      • Medical Center Ophthalmology Associates
    • The Woodlands, Texas, United States, 77384
      • Retina Consultants of Houston
    • Willow Park, Texas, United States, 76087
      • Strategic Clinical Research Group LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 46 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Xlucane; Xlucane (0.05 mL of 10 mg/mL ranibizumab) in the study eye monthly for 52 weeks.	Biological: Ranibizumab; Intravitreal injection
Active Comparator: Lucentis; Lucentis (0.05 mL of 10 mg/mL ranibizumab) in the study eye monthly for 52 weeks.	Biological: Ranibizumab; Intravitreal injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Best Corrected Visual Acuity (BCVA)	Change(s) in BCVA letters at Week 8 compared to baseline using the ETDRS protocol	Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Best Corrected Visual Acuity (BCVA)	Change in BCVA using the ETDRS protocol	Week 4, 12, 16, 24, 36 and 52
Change in total size of choroidal neovascular leakage area	Change in total size of choroidal neovascular leakage area measured by fluorescein angiography (FA)	Week 24 and 52
Change in total size of choroidal neovascularization	Change in total size of choroidal neovascularization measured by FA	Week 24 and 52
Change in Central Foveal Thickness (CFT)	Change in Central Foveal Thickness (CFT) measured by OCT	Week 2, 4, 8, 16, 24, 36 and 52
Percentage of subjects with loss of < 15 letters	Percentage of subjects with loss of < 15 letters using ETDRS	Week 4, 8, 24 and 52
Percentage of subjects with a gain of ≥ 15 letters	Percentage of subjects with a gain of ≥ 15 letters using ETDRS	Week 4, 8, 24 and 52
Intra- or subretinal fluid	Number of subjects without intra- or subretinal fluid (ie, completely dry)	Week 24 and 52
Retinal pigment epithelium detachments	Number of subjects with retinal pigment epithelium detachments	Through study completion
Systemic Ranibizumab concentrations	Systemic Ranibizumab concentrations	Day 0, Day 1 and week 20

Collaborators and Investigators

• Sponsor: Xbrane Biopharma AB
• Collaborators: Stada Arzneimittel AG
• Investigators: Principal Investigator: Anat Loewenstein, Professor, Tel-Aviv Sourasky Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2019
• Primary Completion (Actual): May 11, 2021
• Study Completion (Actual): November 11, 2021

Study Registration Dates

• First Submitted: January 8, 2019
• First Submitted That Met QC Criteria: January 11, 2019
• First Posted (Actual): January 15, 2019

Study Record Updates

• Last Update Posted (Actual): March 14, 2022
• Last Update Submitted That Met QC Criteria: March 11, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab
• Other Study ID Numbers: XBR1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No