Clinical trial NCT03805100: Comparing the Efficacy and Safety of Biosimilar Candidate Xlucane Versus Lucentis® in Patients With nAMD
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Macular Degeneration
Lead sponsor: Xbrane Biopharma AB
Sponsor class: INDUSTRY
Collaborators: name: Stada Arzneimittel AG
First posted: 2019-01-15
Enrollment: 582
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 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.

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).

Primary outcomes:
measure: Change in Best Corrected Visual Acuity (BCVA)
timeFrame: Baseline and Week 8
Secondary outcomes:
measure: Change From Baseline in the Total Size of Choroidal Neovascular Leakage Area in the Study Eye
timeFrame: Baseline and Week 52
measure: Change From Baseline in the Total Size of Choroidal Neovascularisation in the Study Eye
timeFrame: Baseline and week 52
measure: Central Foveal Thickness in the Study Eye
timeFrame: Baseline to week 52
measure: Percentage of Subjects With Loss of <15 BCVA Letters
timeFrame: Baseline to week 52
measure: Percentage of Subjects With Gain of ≥15 BCVA Letters
timeFrame: Baseline to week 52
measure: Subretinal Fluid in the Study Eye
timeFrame: Baseline to week 52
measure: Width of Retinal Pigment Epithelium Detachments in the Study Eye
timeFrame: Baseline to Week 52
measure: Pharmacokinetic Plasma Ranibizumab Concentrations
timeFrame: Day 1 to week 20
measure: Height of Retinal Pigment Epithelium Detachments
timeFrame: Baseline to Week 52
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Retinal Research Institute, LLC
state: Arizona
city: Phoenix
country: United States
facility: Arizona Retina and Vitreous Consultants
state: Arizona
city: Tucson
country: United States
facility: Retina Centers P.C
state: Arizona
city: Arcadia
country: United States
facility: Win Retina
state: California
city: Encino
country: United States
facility: The Retina Partners
state: California
city: Glendora
country: United States
facility: Mark B. Kislinger MD Inc.
state: California
city: Sacramento
country: United States
facility: Retina Consultants Medical Group Inc.
state: California
city: Golden
country: United States
facility: Colorado Retina Associates
state: Colorado
city: Fort Lauderdale
country: United States
facility: Fort Lauderdale Eye Institute
state: Florida
city: Sarasota
country: United States
facility: Sarasota Retina Institute
state: Florida
city: Winter Haven
country: United States
facility: Center for Retina and Macular Disease
state: Florida
city: Augusta
country: United States
facility: Southeast Retina Center
state: Georgia
city: Marietta
country: United States
facility: Georgia Retina
state: Georgia
city: Bloomington
country: United States
facility: Gailey Eye Clinic
state: Illinois
city: Leawood
country: United States
facility: Sabates Eye Centers
state: Kansas
city: New York
country: United States
facility: Retina Vitreous Surgeons of Central New York PC
state: New York
city: Rochester
country: United States
facility: Retina Associates of Western New York
state: New York
city: Ladson
country: United States
facility: Charleston Neuroscience Institute
state: South Carolina
city: Rapid City
country: United States
facility: Black Hills Regional Eye Institute
state: South Dakota
city: Abilene
country: United States
facility: Retina Research Institute of Texas
state: Texas
city: Austin
country: United States
facility: Austin Retina Associates
state: Texas
city: Houston
country: United States
facility: Houston Eye Associates
state: Texas
city: Houston
country: United States
facility: Retina Consultants of Houston
state: Texas
city: San Antonio
country: United States
facility: Medical Center Ophthalmology Associates
state: Texas
city: The Woodlands
country: United States
facility: Retina Consultants of Houston
state: Texas
city: Willow Park
country: United States
facility: Strategic Clinical Research Group LLC
state: Texas
city: Plovdiv
country: Bulgaria
facility: Specialized Eye hospital for active treatment Luxor
city: Sofia
country: Bulgaria
facility: Specialized eye clinic Zrenie
city: Sofia
country: Bulgaria
facility: Specialized Eye hospital for active treatment Acad. Pashev
city: Sofia
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Eye Diseases "Zora"
city: Varna
country: Bulgaria
facility: AMCSMP Eye Clinic St. Petka
city: Brno
country: Czechia
facility: Všeobecná FN v Praze
city: Hradec Králové
country: Czechia
facility: Oční klinika, Fakultní nemocnice
city: Praha
country: Czechia
facility: Faculty Hospital Kralovske Vinohrady
city: Praha
country: Czechia
facility: VFN Ocni klinika
city: Praha
country: Czechia
facility: Axon-Clinical, s.r.o.
city: Tallinn
country: Estonia
facility: Mustame Eye Centre
city: Tallin
country: Estonia
facility: OÜ Dr Kai Noor Silmakabinet
city: Budapest
country: Hungary
facility: Magyar Honvédség Egészségügyi Központ
city: Budapest
country: Hungary
facility: Department of Ophthalmology, Semmelweis University
city: Budapest
country: Hungary
facility: Bajcsy-Zsilinszky Hospital
city: Budapest
country: Hungary
facility: Szent Imre Teaching Hospital
city: Budapest
country: Hungary
facility: Budapest Retina Associates
city: Budapest
country: Hungary
facility: Jahn Ferenc South-Budapest Hospital
city: Debrecen
country: Hungary
facility: University of Debrecen
city: Nyíregyháza
country: Hungary
facility: Szabolcs-Szatmr-Bereg County Hospital
city: Pécs
country: Hungary
facility: Ganglion Medical Center
city: Szombathely
country: Hungary
facility: Markusovszky University Teaching Hospital
city: Zalaegerszeg
country: Hungary
facility: Zalan Megyei Szent Rafael kórház
city: Ahmedabad
country: India
facility: Rising Retina Clinic
city: Beer Sheva
country: Israel
facility: Soroka University Medical Center
city: Haifa
country: Israel
facility: Bnai Zion Medical Center
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Haifa
country: Israel
facility: Carmel Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Jerusalem
country: Israel
facility: Hadassah University Hospital
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Petah Tikva
country: Israel
facility: Rabin Medical Center
city: Reẖovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv
country: Israel
facility: The Tel Aviv Sourasky Medical Centre
city: Zrifin
country: Israel
facility: Asaf Harofe Hospital
city: Riga
country: Latvia
facility: P.Stradins University Hospital
city: Riga
country: Latvia
facility: The Dr Solomatin Eye Center
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian University of Health Sciences Kauno klinikos
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santaros Klinikos
city: Bydgoszcz
country: Poland
facility: Klinika Okulistyczna Oftalmika
city: Katowice
country: Poland
facility: Professor K. Gibinski University Clinical Centre
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 1 w Lublinie
city: Olsztyn
country: Poland
facility: Centrum Diagnostyki i Mikrochirurgii Oka LENS
city: Warszawa
country: Poland
facility: Dr Nowosielska Okulistyka i Chirurgia Oka
city: Warszawa
country: Poland
facility: Retina Okulistyka Sp. z o.o. sp. km
city: Bucharest
country: Romania
facility: Clinica Retina
city: Timişoara
country: Romania
facility: Opticlass Timisoara
city: Cheboksary
country: Russian Federation
facility: FGAU NMRC MNTK Eye Microsurgery n.a. acad. S.N. Fyodorov Cheboksary Branch
city: Kazan
country: Russian Federation
facility: LLC Kuzlyar
city: Moscow
country: Russian Federation
facility: Federal State Budget Scientific Institute of Eye Diseases
city: Moscow
country: Russian Federation
facility: S. Fyodorov Eye Microsurgery Federal State Institution
city: Saint Petersburg
country: Russian Federation
facility: S.Fyodorov Eye Microsurgery Federal State Institution
city: Saint Petersburg
country: Russian Federation
facility: First Pavlov State Medical University of St.Petersburg
city: Banská Bystrica
country: Slovakia
facility: F.D.Roosevelt Hospital
city: Bratislava
country: Slovakia
facility: Univerzitna nemocnica Bratislava, Nemocnica Ruzinov
city: Trenčín
country: Slovakia
facility: Fakultna nemocnica Trencin
city: Žilina
country: Slovakia
facility: Fakultna nemocnica s poliklinikou Zilina
city: Albacete
country: Spain
facility: Hospital General Universitario de Albacete
city: Barcelona
country: Spain
facility: Instituto de Microcirugia Ocular
city: Barcelona
country: Spain
facility: Hospital de Viladecans
city: L'Hospitalet De Llobregat
country: Spain
facility: Bellvitge University Hospital
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro-Majadahonda
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarr
city: Sant Cugat Del Vallès
country: Spain
facility: Hospital General de Catalunya
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Valencia
country: Spain
facility: Unit of Macula. Oftalvist Clinic
city: Valencia
country: Spain
facility: FISABIO-Oftalmologia Medica FOM
city: Valladolid
country: Spain
facility: Hospital Universitario Rio Hortega
city: Zaragoza
country: Spain
facility: Hospital Clinico Universitario Lozano Blesa
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Kharkiv
country: Ukraine
facility: Regional Clinical Hospital Center for Emergency Medical Care And Disaster Medicine
city: Kropyvnytskyi
country: Ukraine
facility: Medical and Diagnostic Centre PE PMC "Acinus"
city: Odessa
country: Ukraine
facility: Filatov Institute of Eye Diseases Tissue Therapy
city: Vinnitsa
country: Ukraine
facility: Clinic of Professor Serhiienko
city: Zaporizhzhia
country: Ukraine
facility: Medical center LTD VISUS
Study officials:
affiliation: Tel-Aviv Sourasky Medical Center
name: Anat Loewenstein, Professor
role: PRINCIPAL_INVESTIGATOR
References: