Wet Age-related macular degeneration (AMD) MedDRA version: 20.0 Level: PT Classification code 10071129 Term: Neovascular age-related macular degeneration System Organ Class: 10015919 - Eye disorders
Conditions
Sponsors
Xbrane Biopharma
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written and signed informed consent form obtained at Screening before any study related procedures are performed. 2. Willingness and ability to undertake all scheduled visits and assessments as judged by the investigator. 3. 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: a. The area of CNV must be = 50% of the total lesion area in the study eye, and b. Total lesion area = 9.0 disc areas (DA) in size (including blood, scars, and neovascularization) as assessed by FA in the study eye 4. BCVA of = 73 and = 49 ETDRS letter score in the study eye using the ETDRS chart (20/40 to 20/100 Snellen equivalent) at Screening. 5. Fellow eye should not be expected to need any anti-VEGF treatment for the duration of study participation. 6. Age = 50 years at Screening. 7. 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 the informed consent form and for the duration of study participation through 3 months after the last dose of study drug. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 180 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 400
Exclusion criteria
Exclusion criteria: 1. Any previous intervention, including pharmacological treatment, laser, and/or surgery for wAMD in either eye; (Exception: Vitamin supplementation for AMD prevention). 2. Any previous vitreoretinal surgery in the study eye for any cause. 3. Any previous IVT treatment, including any anti-VEGF medications, steroids, and/or any other investigational medication in either eye. 4. The use of long-acting steroids, either systemic or intraocular in any eye, in the 18 months before planned initiation of study treatment. (Note: Current or planned Iluvien® [fluocinolone acetonide intravitreal], implantation during the study is prohibited.) 5. 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. 6. Choroidal neovascularization in either eye due to non-AMD causes (eg, DME, RVO, ocular histoplasmosis, trauma) as assessed by FA and confirmed by central reading center. 7. Active or recent (within 28 days prior to Randomization) intraocular, extraocular, and periocular inflammation or infection in either eye. 8. History of idiopathic or autoimmune-associated uveitis in either eye. 9. Infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye. 10. Unmedicated intraocular pressure (IOP) = 30 mm Hg at Screening in either eye. 11. Topical ocular corticosteroids administered for = 30 consecutive days in the study eye within 90 days prior to Screening. 12. Spherical equivalent of the refractive error in the study eye demonstrating more than 8 diopters of myopia. 13. Corneal transplant or corneal dystrophy in the study eye. 14. History of rhegmatogenous retinal detachment in the study eye. 15. History of macular hole in the study eye. 16. Retinal pigment epithelial tear or rip involving the macula in the study eye as assessed by FA and confirmed by the central reading center. 17. Current vitreous hemorrhage in the study eye. 18. 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. 19. 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 no later than 4 weeks prior to Screening. 20. 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. 21. Significant media opacities (including cataract) in the study eye interfering with BCVA assessment or fundus imaging (FA/FP/OCT). 22. 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 (IOL) implantation. 23. Presence of advanced glaucoma or optic neuropathy that involves or threatens the central visual field in the study eye (as judged by the investigator). 24. History of glaucoma filtering surgery or ALT in the study eye (Exception: Laser iridotomy and SLT are allowed). 25. Uncontrolled ocular glaucoma or hypertension in the study eye, defined as IOP = 25 mm Hg despite treatment with anti-glaucoma medication
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to demonstrate that the biosimilar candidate Xlucane is equivalent to Lucentis® in subjects with wAMD as assessed by the change in BCVA from Baseline to Week 8.;Secondary Objective: The secondary objectives of the study are as follows: • Evaluate the efficacy of Xlucane vs Lucentis® in subjects with wAMD based on central foveal thickness (CFT) measured by spectral domain optical coherence tomography (SD-OCT), area of choroidal neovascularization, and presence of leakage assessed by fundus fluorescein angiography (FFA) • Evaluate the safety of Xlucane vs Lucentis® • Evaluate the systemic exposure of Xlucane vs Lucentis® in subjects participating in pharmacokinetics (PK) evaluation • Evaluate immunogenicity (ie, anti-ranibizumab antibodies and NAb) of Xlucane vs Lucentis®;Timepoint(s) of evaluation of this end point: When all subjects have completed their 6-month assessments, an unmasked analysis of efficacy and safety endpoints as well as PK and immunogenicity will be performed. The aim of this analysis is to obtain results without waiting for the full follow-up of the subjects. This analysis will not affect the further conduct of the study.;Primary end point(s): 1. Efficacy Endpoint The change in BCVA letters at Week 8 compared to Baseline using the ETDRS protocol will be analyzed using a mixed model for repeated measures (MMRM). An MMRM approach will be fitted with geographical region of the country where enrolled, visit, eye color (light iris vs dark iris), treatment, and treatment-by-visit interaction as fixed effects, with the baseline BCVA letters and baseline BCVA letters-by-visit interaction as a covariates. The treatment differences from the model at Week 8 will be evaluated and a 95% two-sided CI for the least squares mean difference between groups will be calculated. To prove the 2 products to be biosimilar, the confidence limits for this difference have to be within the equivalence margin of 3 letters | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints The following continuous secondary endpoints will be analyzed in a similar fashion to the primary efficacy endpoint: • Change in BCVA letters at Week 4, Week 12, Week 16, Week 24, Week 36 and Week 52 compared to Baseline using the ETDRS protocol • Change in total size of choroidal neovascular leakage area in the study eye measured by FA at Week 24 and Week 52 compared to Baseline • Change in total size of choroidal neovascularization in the study eye measured by FA at Week 24 and Week 52 compared to Baseline • Change in Central Foveal Thickness (CFT) in the study eye measured by OCT at Week 2, Week 4, Week 8,Week 16, Week 24, Week 36 and Week 52 compared to Baseline • Changes in the size and/or number of intraretinal cystoid space (cysts), subretinal fluid, and retinal pigment epithelium detachments in the study eye measured by qualitative morphology-based OCT The following secondary endpoints will be analysed using a Cochran-Mantel-Haenzel test and the 95% stratified Newcombe CI (by randomization stratification group) will be presented for the difference in proportions between groups. • Percentage of subjects with loss of <15 letters using ETDRS, evaluated as change at Week 4, Week 8, Week 24, and Week 52 compared to Baseline in the study eye • Percentage of subjects with gain of =15 letters using ETDRS, evaluated as change at Week 4, Week 8, Week 24, and Week 52 compared to Baseline in the study eye • Percentage of subjects without intra- or subretinal fluid in the study eye (ie, completely dry) at Week 24 and Week 52 • Percentage of subjects with retinal pigment;Timepoint(s) of evaluation of this end point: Timepoints for evaluation of secondary endpoints are listed in the endpoint description above. | — |
Countries
Bulgaria, Czech Republic, Estonia, Hungary, India, Israel, Latvia, Lithuania, Poland, Romania, Russian Federation, Slovakia, Spain, Ukraine, United States
Contacts
Public ContactDina Jurman
Xbrane Biopharma
Outcome results
None listed