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

Sponsor
Xbrane Biopharma AB (Industry)
Overall Status
Completed
CT.gov ID
NCT03805100
Collaborator
Stada Arzneimittel AG (Industry)
582
Enrollment
102
Locations
2
Arms
30.8
Actual Duration (Months)
5.7
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease Intervention/Treatment Phase
  • Biological: Ranibizumab
 Phase 3

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 Design

Study Type:
Interventional
Actual Enrollment :
582 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Outcomes Assessor)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Apr 19, 2019
Actual Primary Completion Date :
May 11, 2021
Actual Study Completion Date :
Nov 11, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

  1. Change in Best Corrected Visual Acuity (BCVA) [Week 8]

    Change(s) in BCVA letters at Week 8 compared to baseline using the ETDRS protocol

Secondary Outcome Measures

  1. Change in Best Corrected Visual Acuity (BCVA) [Week 4, 12, 16, 24, 36 and 52]

    Change in BCVA using the ETDRS protocol

  2. Change in total size of choroidal neovascular leakage area [Week 24 and 52]

    Change in total size of choroidal neovascular leakage area measured by fluorescein angiography (FA)

  3. Change in total size of choroidal neovascularization [Week 24 and 52]

    Change in total size of choroidal neovascularization measured by FA

  4. Change in Central Foveal Thickness (CFT) [Week 2, 4, 8, 16, 24, 36 and 52]

    Change in Central Foveal Thickness (CFT) measured by OCT

  5. Percentage of subjects with loss of < 15 letters [Week 4, 8, 24 and 52]

    Percentage of subjects with loss of < 15 letters using ETDRS

  6. Percentage of subjects with a gain of ≥ 15 letters [Week 4, 8, 24 and 52]

    Percentage of subjects with a gain of ≥ 15 letters using ETDRS

  7. Intra- or subretinal fluid [Week 24 and 52]

    Number of subjects without intra- or subretinal fluid (ie, completely dry)

  8. Retinal pigment epithelium detachments [Through study completion]

    Number of subjects with retinal pigment epithelium detachments

  9. Systemic Ranibizumab concentrations [Day 0, Day 1 and week 20]

    Systemic Ranibizumab concentrations

Eligibility Criteria

Criteria

Ages Eligible for Study:
50 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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).

Contacts and Locations

Locations

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

Sponsors and Collaborators

  • Xbrane Biopharma AB
  • Stada Arzneimittel AG

Investigators

  • Principal Investigator: Anat Loewenstein, Professor, Tel-Aviv Sourasky Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Xbrane Biopharma AB
ClinicalTrials.gov Identifier:
NCT03805100
Other Study ID Numbers:
  • XBR1001
First Posted:
Jan 15, 2019
Last Update Posted:
Mar 14, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Macular Degeneration
Ranibizumab

Study Results

No Results Posted as of Mar 14, 2022