A Study to Compare SB15 (Proposed Aflibercept Biosimilar) to Eylea in Subjects With Neovascular Age-related Macular Degeneration (AMD)
Condition: Neovascular Age-related Macular Degeneration
MeSH terms: Macular Degeneration; Wet Macular Degeneration
Intervention: SB15 (Proposed aflibercept biosimilar); Eylea (Aflibercept)
Intervention description: Subjects randomized into SB15 group will receive SB15 2 mg (0.05 mL) via intravitreal injection every 4 weeks for the first 3 months, followed by 2 mg (0.05 mL) once every 8 weeks until Week 48. Starting at Week 32, subjects transited from Eylea to SB15 will receive SB15 2 mg (0.05 mL) via intravitreal injection every 8 weeks.; Subjects randomized into Eylea group will receive Eylea 2 mg (0.05 mL) via intravitreal injection every 4 weeks for the first 3 months, followed by 2 mg (0.05 mL) once every 8 weeks until Week 48.
Intervention MeSH terms: Aflibercept
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 449.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No

Summary:

      This is a randomised, double-masked, parallel group, multicentre study to evaluate the
      efficacy, safety, Pharmacokinetics (PK), and immunogenicity of SB15 compared to Eylea® in
      subjects with neovascular AMD.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age ≥ 50 years at Screening

          2. Treatment naïve, *active subfoveal choroidal neovascularisation (CNV) lesion secondary
             to AMD in the study eye

          3. The area of CNV must occupy at least 50% of total lesion in the study eye

          4. Total lesion area ≤ 9.0 Disc Areas (DA) in size (including blood, scars, and
             neovascularisation) in the study eye

          5. BCVA of 20/40 to 20/200 (letter score of 73 to 34, inclusive) using ETDRS charts or
             2702 series Number charts in the study eye at Screening and at Week 0 (Day 1) prior to
             randomisation

          6. Non-childbearing potential female, OR childbearing potential female subjects or male
             subjects with their (respectively male or female) partners who agree to use at least
             two forms of appropriate contraception method that can achieve a failure rate of less
             than 1% per year from Screening until 3 months after the last IVT injection of IP

          7. Written informed consent form (ICF) must be obtained from the subject prior to any
             study related procedure

          8. Willingness and ability to undertake all scheduled visits and assessments

        Exclusion Criteria:

          1. Study eye: Sub- or intra-retinal haemorrhage that comprises more than 50% of the
             entire lesion or presence of blood with the size of 1 DA or more involving the centre
             of fovea

          2. Study eye: Scar, fibrosis, or atrophy involving the centre of the fovea

          3. Study eye: Presence of CNV due to other causes, such as ocular histoplasmosis, trauma,
             multifocal choroiditis, angioid streaks, history of choroidal rupture, or pathologic
             myopia

          4. Study eye: Presence of retinal pigment epithelial tears or rips involving the macula

          5. Study eye: Presence of macular hole at any stage

          6. Study eye: Any concurrent macular abnormality other than AMD which could affect
             central vision or the efficacy of IP

          7. Study eye: Any concurrent ocular condition which, in the opinion of the Investigator,
             could either confound the interpretation of efficacy and safety of IP or require
             medical or surgical intervention during the study period

          8. Either eye: History or clinical evidence of diabetic retinopathy (except for mild
             non-proliferative diabetic retinopathy) or diabetic macular oedema (DME)

          9. Study eye: Current vitreous haemorrhage

         10. Either eye: Any previous IVT anti-vascular endothelial growth factor (VEGF) treatment

         11. Any previous systemic anti-VEGF treatment

         12. Study eye: History of treatment involving macula such as macular laser
             photocoagulation, photodynamic therapy (PDT), transpupillary thermotherapy (TTT),
             radiation therapy, or any ocular treatment for neovascular AMD

         13. Any systemic treatment or therapy (including prescribed herbal medication) to treat
             neovascular AMD within 30 days prior to randomisation. However, dietary supplements,
             vitamins, or minerals will be allowed.

         14. Study eye: History of vitrectomy, scleral buckling (encircling), glaucoma filtration
             surgery, corneal transplantation, or pan-retinal photocoagulation

         15. Study eye: Previous ocular (intraocular and peribulbar) corticosteroids
             injection/implant within 1 year prior to randomisation

         16. Study eye: Topical ocular corticosteroids administered for ≥ 30 consecutive days or
             for ≥ 60 nonconsecutive days within 90 days prior to randomisation

         17. Use of systemic corticosteroids for 30 or more consecutive days within 90 days prior
             to randomization (inhaled steroid is permitted).

         18. Study eye: Any other intraocular surgery or periocular surgery within 90 days prior to
             randomisation, except for lid surgery, which may not have taken place within 30 days
             prior to randomisation.

         19. Current use of medications known to be toxic to the lens, retina, or optic nerve at
             Screening.

         20. Study eye: Previous radiation therapy near the region of the study eye

         21. Previous participation in clinical studies with IP to treat neovascular AMD in either
             eye.

         22. Previous participation in clinical studies with IP to treat disease other than
             neovascular AMD within 90 days prior to randomisation (excluding dietary
             supplementary, vitamins, and minerals).

         23. Subject with only one functional eye (defined as BCVA of counting finger or less on
             the eye with worse vision)

         24. Study eye: Spherical equivalent of the refractive error demonstrating more than 6
             diopters of myopia. For subjects who have undergone previous refractive or cataract
             surgery in the study eye, the preoperative refractive error in the study eye cannot
             exceed 6 diopters of myopia.

         25. Study eye: Aphakia or absence of the posterior capsule (unless it occurred as a result
             of a YAG laser posterior capsulotomy in association with prior posterior chamber IOL
             implantation)

         26. Either eye: Active or suspected ocular and periocular infection at Screening or at
             randomisation

         27. Either eye: Active intraocular inflammation including scleritis at Screening or at
             randomisation

         28. Either eye: History of idiopathic or autoimmune-associated uveitis

         29. Study eye: Uncontrolled ocular hypertension (defined as intraocular pressure [IOP] ≥
             25 mmHg despite treatment with anti-glaucoma medication) at Screening

         30. Known allergic reactions and/or hypersensitivity to any component of Eylea or SB15

         31. History of allergy to the fluorescein sodium for injection in angiography

         32. History of a medical condition that would preclude scheduled study visits or safe use
             of IP in the opinion of the Investigator

         33. Uncontrolled systemic disease including but not limited to uncontrolled diabetes
             mellitus (in the opinion of the Investigator), uncontrolled systemic hypertension
             (systolic blood pressure ≥ 180 mmHg and/or diastolic blood pressure ≥ 100 mmHg on
             optimal medical regimen), or uncontrolled atrial fibrillation (resting heart rate ≥
             110 beats per minutes) at Screening

         34. Stroke, transient ischaemic attacks, or myocardial infarction within 180 days prior to
             randomisation

         35. History of recurrent significant infections and/or current treatment for systemic
             infection

         36. Severe renal impairment with dialysis or a history of renal transplant

         37. Malignancy (other than non-melanoma skin cancer) under treatment or with history of
             metastatic disease

         38. Women of childbearing potential who are pregnant, planning to become pregnant,
             lactating, or not using adequate birth control, as specified in protocol. For women of
             childbearing potential, a serum pregnancy test must result negative at Screening.

         39. Employees of investigational sites, individuals directly involved with the conduct of
             the study