Comparing the Efficacy and Safety of Biosimilar Candidate Xlucane Versus Lucentis® in Patients With nAMD
Condition: Macular Degeneration
MeSH terms: Macular Degeneration
Intervention: Ranibizumab
Intervention description: Intravitreal injection
Intervention MeSH terms: Ranibizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Enrollment: 582.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No

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).
    

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).