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

Macular Degeneration Clinical Trial

— XPLORE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03805100
• Other study ID #: XBR1001
• Status: Completed
• Phase: Phase 3
• Start date: April 19, 2019
• Est. completion date: November 11, 2021

Study information

• Verified date: February 2023
• Source: Xbrane Biopharma AB
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 582
• Est. completion date: November 11, 2021
• Est. primary completion date: May 11, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Macular Degeneration

Intervention

Biological:
• Ranibizumab
Intravitreal injection

Locations

Country	Name	City	State
Bulgaria	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
Czechia	Všeobecná FN v Praze	Brno
Czechia	Ocní klinika, Fakultní nemocnice	Hradec Králové
Czechia	Axon-Clinical, s.r.o.	Praha
Czechia	Faculty Hospital Kralovske Vinohrady	Praha
Czechia	VFN Ocni klinika	Praha
Estonia	OÜ Dr Kai Noor Silmakabinet	Tallin
Estonia	Mustame Eye Centre	Tallinn
Hungary	Bajcsy-Zsilinszky Hospital	Budapest
Hungary	Budapest Retina Associates	Budapest
Hungary	Department of Ophthalmology, Semmelweis University	Budapest
Hungary	Jahn Ferenc South-Budapest Hospital	Budapest
Hungary	Magyar Honvédség Egészségügyi Központ	Budapest
Hungary	Szent Imre Teaching 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
India	Rising Retina Clinic	Ahmedabad
Israel	Soroka University Medical Center	Beer Sheva
Israel	Bnai Zion Medical Center	Haifa
Israel	Carmel Medical Center	Haifa
Israel	Rambam Health Care Campus	Haifa
Israel	Hadassah University Hospital	Jerusalem
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Meir Medical Center	Kfar Saba
Israel	Rabin Medical Center	Petah Tikva
Israel	Kaplan Medical Center	Re?ovot
Israel	The Tel Aviv Sourasky Medical Centre	Tel Aviv
Israel	Asaf Harofe Hospital	Zrifin
Latvia	P.Stradins University Hospital	Riga
Latvia	The Dr Solomatin Eye Center	Riga
Lithuania	Hospital of Lithuanian University of Health Sciences Kauno klinikos	Kaunas
Lithuania	Vilnius University Hospital Santaros Klinikos	Vilnius
Poland	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	Warszawa
Poland	Retina Okulistyka Sp. z o.o. sp. km	Warszawa
Romania	Clinica Retina	Bucharest
Romania	Opticlass Timisoara	Timisoara
Russian Federation	FGAU NMRC MNTK Eye Microsurgery n.a. acad. S.N. Fyodorov Cheboksary Branch	Cheboksary
Russian Federation	LLC Kuzlyar	Kazan
Russian Federation	Federal State Budget Scientific Institute of Eye Diseases	Moscow
Russian Federation	S. Fyodorov Eye Microsurgery Federal State Institution	Moscow
Russian Federation	First Pavlov State Medical University of St.Petersburg	Saint Petersburg
Russian Federation	S.Fyodorov Eye Microsurgery Federal State Institution	Saint Petersburg
Slovakia	Fakultna nemocnica s poliklinikou Zilina	Žilina
Slovakia	F.D.Roosevelt Hospital	Banská Bystrica
Slovakia	Univerzitna nemocnica Bratislava, Nemocnica Ruzinov	Bratislava
Slovakia	Fakultna nemocnica Trencin	Trencín
Spain	Hospital General Universitario de Albacete	Albacete
Spain	Hospital de Viladecans	Barcelona
Spain	Instituto de Microcirugia Ocular	Barcelona
Spain	Bellvitge University Hospital	L'Hospitalet De Llobregat
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Universitario Puerta de Hierro-Majadahonda	Madrid
Spain	Clinica Universidad de Navarr	Pamplona
Spain	Hospital General de Catalunya	Sant Cugat Del Vallès
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	FISABIO-Oftalmologia Medica FOM	Valencia
Spain	Unit of Macula. Oftalvist Clinic	Valencia
Spain	Hospital Universitario Rio Hortega	Valladolid
Spain	Hospital Clinico Universitario Lozano Blesa	Zaragoza
Spain	Hospital Universitario Miguel Servet	Zaragoza
Ukraine	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	Odessa
Ukraine	Clinic of Professor Serhiienko	Vinnitsa
Ukraine	Medical center LTD VISUS	Zaporizhzhia
United States	Retina Research Institute of Texas	Abilene	Texas
United States	Win Retina	Arcadia	California
United States	Southeast Retina Center	Augusta	Georgia
United States	Austin Retina Associates	Austin	Texas
United States	Gailey Eye Clinic	Bloomington	Illinois
United States	The Retina Partners	Encino	California
United States	Fort Lauderdale Eye Institute	Fort Lauderdale	Florida
United States	Retinal Research Institute, LLC	Gilbert	Arizona
United States	Mark B. Kislinger MD Inc.	Glendora	California
United States	Colorado Retina Associates	Golden	Colorado
United States	Houston Eye Associates	Houston	Texas
United States	Retina Consultants of Houston	Houston	Texas
United States	Charleston Neuroscience Institute	Ladson	South Carolina
United States	Sabates Eye Centers	Leawood	Kansas
United States	Georgia Retina	Marietta	Georgia
United States	Retina Vitreous Surgeons of Central New York PC	New York	New York
United States	Arizona Retina and Vitreous Consultants	Phoenix	Arizona
United States	Black Hills Regional Eye Institute	Rapid City	South Dakota
United States	Retina Associates of Western New York	Rochester	New York
United States	Retina Consultants Medical Group Inc.	Sacramento	California
United States	Medical Center Ophthalmology Associates	San Antonio	Texas
United States	Sarasota Retina Institute	Sarasota	Florida
United States	Retina Consultants of Houston	The Woodlands	Texas
United States	Retina Centers P.C	Tucson	Arizona
United States	Strategic Clinical Research Group LLC	Willow Park	Texas
United States	Center for Retina and Macular Disease	Winter Haven	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Xbrane Biopharma AB	Stada Arzneimittel AG

Countries where clinical trial is conducted

United States,  Bulgaria,  Czechia,  Estonia,  Hungary,  India,  Israel,  Latvia,  Lithuania,  Poland,  Romania,  Russian Federation,  Slovakia,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Best Corrected Visual Acuity (BCVA)	Change(s) in BCVA letters at Week 8 compared to baseline using the ETDRS protocol	Baseline and Week 8
Secondary	Change From Baseline in the Total Size of Choroidal Neovascular Leakage Area in the Study Eye	Change in the total size of choroidal neovascular leakage area in the study eye week 52 compared to baseline measured by Fluorescein Angiography	Baseline and Week 52
Secondary	Change From Baseline in the Total Size of Choroidal Neovascularisation in the Study Eye	Change From Baseline in the Total Size of Choroidal Neovascularisation in the Study Eye Measured by Fluorescein Angiography	Baseline and week 52
Secondary	Central Foveal Thickness in the Study Eye	Central Foveal Thickness in the Study Eye Measured by Optical Coherence Tomography	Baseline to week 52
Secondary	Percentage of Subjects With Loss of <15 BCVA Letters	Percentage of Subjects With Loss of <15 BCVA Letters Compared to Baseline in the Study Eye	Baseline to week 52
Secondary	Percentage of Subjects With Gain of =15 BCVA Letters	Percentage of Subjects With Gain of =15 BCVA Letters Compared to Baseline in the Study Eye	Baseline to week 52
Secondary	Subretinal Fluid in the Study Eye	Change from Baseline in the Amount of Subretinal Fluid in the Study Eye Measured by OCT	Baseline to week 52
Secondary	Width of Retinal Pigment Epithelium Detachments in the Study Eye	Change from Baseline in the Width of Retinal Pigment Epithelium Detachments in the Study Eye Measured by OCT	Baseline to Week 52
Secondary	Pharmacokinetic Plasma Ranibizumab Concentrations	Pharmacokinetic Plasma Ranibizumab Concentrations (sub-study)	Day 1 to week 20
Secondary	Height of Retinal Pigment Epithelium Detachments	Change from Baseline in the Height of Retinal Pigment Epithelium Detachments in the Study Eye Measured by OCT	Baseline to Week 52