Clinical trial NCT04450329: A Study to Compare SB15 (Proposed Aflibercept Biosimilar) to Eylea in Subjects With Neovascular Age-related Macular Degeneration (AMD)
Official title: A Phase III Randomised, Double-masked, Parallel Group, Multicentre Study to Compare the Efficacy, Safety, Pharmacokinetics, and Immunogenicity Between SB15 (Proposed Aflibercept Biosimilar) and Eylea® in Subjects With Neovascular Age-related Macular Degeneration
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Neovascular Age-related Macular Degeneration
Lead sponsor: Samsung Bioepis Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-06-29
Enrollment: 449
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: Subjects will be randomised in a 1:1 ratio to receive either SB15 or Eylea® (administered via intravitreal \[IVT\] injection 2 mg \[0.05 mL\] every 4 weeks for the first 3 months (i.e., at Weeks 0, 4, and 8), followed by 2 mg \[0.05 mL\] once every 8 weeks). At Week 32, subjects in Eylea® treatment group will be randomised again in a 1:1 ratio to either continue on Eylea® treatment or be transitioned to SB15 treatment. In the 8-week treatment cycle, IPs (SB15 or Eylea®) will be administered up to Week 48, and the last assessment will be done at Week 56, corresponding to the end of follow-up for all subjects.

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

Primary outcomes:
measure: Change From Baseline in Best Corrected Visual Acuity (BCVA)
timeFrame: Baseline and Week 8
Secondary outcomes:
Other outcomes:
Locations:
city: Colorado Springs
country: United States
facility: SB Investigative Site
state: Colorado
city: Chevy Chase
country: United States
facility: SB Investigative Site
state: Maryland
city: Abilene
country: United States
facility: SB Investigative Site
state: Texas
city: Osijek
country: Croatia
facility: SB Investigative Site
city: Rijeka
country: Croatia
facility: SB Investigative Site
city: Brno
country: Czechia
facility: SB Investigative Site
city: Hradec Králové
country: Czechia
facility: SB Investigative Site
city: Praha 10
country: Czechia
facility: SB Investigative Site
city: Praha 5
country: Czechia
facility: SB Investigative Site
city: Kohtla-Järve
country: Estonia
facility: SB Investigative Site
city: Tallinn
country: Estonia
facility: SB Investigative Site
city: Budapest
country: Hungary
facility: SB Investigative Site
city: Debrecen
country: Hungary
facility: SB Investigative Site
city: Pécs
country: Hungary
facility: SB Investigative Site
city: Szeged
country: Hungary
facility: SB Investigative Site
city: Zalaegerszeg
country: Hungary
facility: SB Investigative Site
city: Aichi
country: Japan
facility: SB Investigative Site
city: Fukuoka
country: Japan
facility: SB Investigative Site
city: Inashiki-gun
country: Japan
facility: SB Investigative Site
city: Kagoshima
country: Japan
facility: SB Investigative Site
city: Nagasaki-Shi
country: Japan
facility: SB Investigative Site
city: Osaka
country: Japan
facility: SB Investigative Site
city: Saitama
country: Japan
facility: SB Investigative Site
city: Tokyo
country: Japan
facility: SB Investigative Site
city: Ansan
country: Korea, Republic of
facility: SB Investigative Site
city: Busan
country: Korea, Republic of
facility: SB Investigative Site
city: Daegu
country: Korea, Republic of
facility: SB Investigative Site
city: Seongnam
country: Korea, Republic of
facility: SB Investigative Site
city: Seoul
country: Korea, Republic of
facility: SB Investigative Site
city: Riga
country: Latvia
facility: SB Investigative Site
city: Bydgoszcz
country: Poland
facility: SB Investigative Site
city: Katowice
country: Poland
facility: SB Investigative Site
city: Kraków
country: Poland
facility: SB Investigative Site
city: Tarnów
country: Poland
facility: SB Investigative Site
city: Łódź
country: Poland
facility: SB Investigative Site
city: Kovrov
country: Russian Federation
facility: SB Investigative Site
city: Moscow
country: Russian Federation
facility: SB Investigative Site
city: Novosibirsk
country: Russian Federation
facility: SB Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: SB Investigative Site
Study officials:
affiliation: Seoul National University Bundang Hospital, South Korea
name: Se Joon Woo
role: PRINCIPAL_INVESTIGATOR
References: