A Study to Compare SB15 (Proposed Aflibercept Biosimilar) to Eylea in Subjects With Neovascular Age-related Macular Degeneration (AMD)

NCT ID: NCT04450329

Last Updated: 2024-02-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 449 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-23
• Study Completion Date: 2022-03-16

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.

Conditions

Neovascular Age-related Macular Degeneration

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

SB15 (Proposed aflibercept biosimilar)

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.

Group Type: EXPERIMENTAL

SB15 (Proposed aflibercept biosimilar)

Intervention Type: DRUG

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.

Eylea (Aflibercept)

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.

At Week 32, subjects in Eylea group will re-randomized into SB15 or Eylea group. After re-randomization, subjects transited to SB15 group will receive SB15 2 mg (0.05 mL) once every 8 weeks until Week 48 and subjects remaining in Eylea group will continue to receive Eylea 2 mg (0.05 mL) once every 8 weeks until Week 48.

Group Type: ACTIVE_COMPARATOR

SB15 (Proposed aflibercept biosimilar)

Intervention Type: DRUG

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.

Eylea (Aflibercept)

Intervention Type: DRUG

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.

Interventions

SB15 (Proposed aflibercept biosimilar)

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.

Intervention Type: DRUG

Eylea (Aflibercept)

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 Type: DRUG

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

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Samsung Bioepis Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Se Joon Woo

Role: PRINCIPAL_INVESTIGATOR

Seoul National University Bundang Hospital, South Korea

Locations

SB Investigative Site

Colorado Springs, Colorado, United States

SB Investigative Site

Chevy Chase, Maryland, United States

SB Investigative Site

Abilene, Texas, United States

SB Investigative Site

Osijek, , Croatia

SB Investigative Site

Rijeka, , Croatia

SB Investigative Site

Brno, , Czechia

SB Investigative Site

Hradec Králové, , Czechia

SB Investigative Site

Prague, , Czechia

SB Investigative Site

Kohtla-Järve, , Estonia

SB Investigative Site

Tallinn, , Estonia

SB Investigative Site

Budapest, , Hungary

SB Investigative Site

Debrecen, , Hungary

SB Investigative Site

Pécs, , Hungary

SB Investigative Site

Szeged, , Hungary

SB Investigative Site

Zalaegerszeg, , Hungary

SB Investigative Site

Aichi, , Japan

SB Investigative Site

Fukuoka, , Japan

SB Investigative Site

Inashiki-gun, , Japan

SB Investigative Site

Kagoshima, , Japan

SB Investigative Site

Nagasaki, , Japan

SB Investigative Site

Osaka, , Japan

SB Investigative Site

Saitama, , Japan

SB Investigative Site

Tokyo, , Japan

SB Investigative Site

Riga, , Latvia

SB Investigative Site

Bydgoszcz, , Poland

SB Investigative Site

Katowice, , Poland

SB Investigative Site

Krakow, , Poland

SB Investigative Site

Lodz, , Poland

SB Investigative Site

Tarnów, , Poland

SB Investigative Site

Kovrov, , Russia

SB Investigative Site

Moscow, , Russia

SB Investigative Site

Novosibirsk, , Russia

SB Investigative Site

Saint Petersburg, , Russia

SB Investigative Site

Ansan, , South Korea

SB Investigative Site

Busan, , South Korea

SB Investigative Site

Daegu, , South Korea

SB Investigative Site

Seongnam, , South Korea

SB Investigative Site

Seoul, , South Korea

Countries

United States; Croatia; Czechia; Estonia; Hungary; Japan; Latvia; Poland; Russia; South Korea

References

Woo SJ, Bradvica M, Vajas A, Sagong M, Ernest J, Studnicka J, Veith M, Wylegala E, Patel S, Yun C, Orski M, Astakhov S, Toth-Molnar E, Csutak A, Enyedi L, Kim T, Oh I, Jang H, Sadda SR. Efficacy and Safety of the Aflibercept Biosimilar SB15 in Neovascular Age-Related Macular Degeneration: A Phase 3 Randomized Clinical Trial. JAMA Ophthalmol. 2023 Jul 1;141(7):668-676. doi: 10.1001/jamaophthalmol.2023.2260.

Reference Type: DERIVED

PMID: 37289448 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

SB15-3001

Identifier Type: -

Identifier Source: org_study_id