Phase 3 study to Compare the Efficacy and Safety of ALT L9 Versus Eylea in Patients With Neovascular Age Related Macular Degeneration

JRCT ID: jRCT2071210144

Registered date:31/03/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Neovascular Age-Related Macular Degeneration
• Date of first enrollment: 25/05/2022
• Target sample size: 36
• Countries of recruitment: Bulgaria,Japan,the Czech Republic,Japan,Estonia,Japan,Hungary,Japan,Latvia,Japan,Lithuania,Japan,Poland,Japan,Russia,Japan,Slovakia,Japan,South Korea,Japan,Spain,Japan,Ukraine,Japan,Austria,Japan
• Study type: Interventional

Intervention(s)

In this study, ALT-L9 40 mg/mL (2 mg/50 micro L aflibercept) will be administered by ophthalmic IVT injection in the study eye q4w at baseline, Week 4, and Week 8 and thereafter q8w at Weeks 16, 24, 32, 40, and 48 for 48 weeks (approximately 12 months) in subjects with nAMD who are randomized to receive ALT L9.
Eylea 40 mg/mL (2 mg/50 micro L aflibercept) will also be administered by ophthalmic IVT injection in the study eye q4w at baseline, Week 4, and Week 8 and thereafter q8w at Weeks 16, 24, 32, 40, and 48 for 48 weeks (approximately 12 months) in subjects with nAMD who are randomized to receive Eylea.

Outcome(s)

• Primary Outcome: Change from baseline in BCVA at Week 8 as measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score

Key inclusion & exclusion criteria

• Age minimum: >= 50age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1.Able and willing to read, understand, and sign the informed consent form (ICF). The signed ICF must be obtained before any study-related procedures are performed. The subject must be willing and able to undertake all scheduled visits and assessments as judged by the investigator
2.Subjects aged 50 years or older at the time of screening, when obtaining written informed consent
3.BCVA of 20/40 to 20/200 (both inclusive) in the study eye using the ETDRS letter chart (<=73 and >=34 ETDRS letters) at screening and at Day 1 before randomization
4.Newly diagnosed, treatment-naive, active subfoveal or juxtafoveal CNV lesion secondary to age-related macular degeneration in the study eye. Active CNV means the presence of leakage as evidenced by FA and intraretinal or subretinal fluid as evidenced by SD OCT that is confirmed by the central reading center (CRC) during screening
5.Total lesion area of <=9.0 disc areas (<=22.86 mmx2) in size (including blood, scars, and neovascularization) in the study eye as assessed by FA and confirmed by the CRC before randomization
6.The area of CNV must be >=50% of the total lesion area in the study eye confirmed by the CRC before randomization
7.Female subjects must agree to use a highly effective method of contraception consistent with local regulations during the course of the study and for at least 90 days after the last dose of the study drug (excluding women who are not of childbearing potential).
Contraception is not required if the subject or his/her partner has been surgically sterilized with documentation of surgical success at least 24 weeks before the date of informed consent.
a)Male subjects of reproductive potential must be willing to completely abstain from sexual intercourse or agree to use an appropriate method of contraception from the time of signing the ICF and for the duration of study participation through 90 days after the last dose of the study drug. (The investigator and each subject will determine the appropriate method of contraception for the subject during study participation.)
b)Subjects must agree to refrain from donating sperm (male subjects) and ova (female subjects) from screening through 90 days after receiving the last dose of study drug.

Exclude criteria

Considerations for study eye
1. Previous ocular treatment/surgery (including any macular laser or photodynamic therapy) for nAMD in the study eye
2. Any previous IVT anti vascular endothelial growth factor (anti VEGF) treatment (eg, bevacizumab, aflibercept, ranibizumab, or brolucizumab) in the study eye
3. Subretinal or intraretinal hemorrhage in the study eye involving 50% or more of the total lesion area, or with a size of >=1 disc area (>=2.54 mmx2) if involving the fovea, as assessed by FA and confirmed by the CRC
4. Subfoveal fibrosis or atrophy in the study eye as assessed by FA and confirmed by the CRC
5. Fibrosis exceeding 50% of the total lesion size in the study eye as assessed by FA and confirmed by the CRC
6. Retinal pigment epithelial rips or tears involving the macula in the study eye as assessed by FA or SD-OCT and confirmed by the CRC
7. Previous IVT surgery or scleral buckling in the study eye
8. Other intraocular surgery (including cataract surgery, laser-assisted in situ keratomileusis (LASIK), or Yttrium Aluminum Garnet (YAG) laser) or periocular surgery in the study eye within 90 days before screening, except for eyelid surgery within 30 days before screening
9. Corneal transplant in the study eye
10. 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 or could interfere with visual acuity, optical imaging, or safety assessments defined by the study protocol
11. Aphakia or absence of the posterior capsule in the study eye, unless it occurred as a result of a YAG laser posterior capsulotomy in association with prior posterior chamber intraocular lens implantation
12. Current vitreous hemorrhage in the study eye
13. History of retinal detachment in the study eye
14. History of macular hole in the study eye
15. Uncontrolled ocular hypertension in the study eye, defined as an IOP of >=25 mm Hg despite treatment with antiglaucoma medication
16. Presence of advanced glaucoma or optic neuropathy that involves or threatens the central visual field in the study eye
17. History of any glaucoma filtering surgery, corneal transplantation, or panretinal photocoagulation; such therapies are not allowed during the study in the study eye
18. Spherical equivalent of the refractive error in the study eye demonstrating more than 8 diopters of myopia
19. Use of ongoing topical ocular corticosteroids at screening or administrated for >=30 consecutive days in the study eye within 90 days before screening, or the use of intraocular corticosteroid implants in the study eye within 180 days before screening for Ozurdex or within 3 years before screening for Iluvien
20. Prior therapeutic radiation in the study eye region
21. Subjects with any diagnosis and / or signs of nAMD requiring IVT anti-VEGF treatment in the fellow eye at screening or, in the opinion of the investigator, who are expected to need such treatments.
22. Use of any anti-VEGF treatment in the fellow eye within 90 days before screening
23. The BCVA of the fellow eye is worse than 20/200 (or <34 ETDRS letters)
Considerations for either eye
24. CNV in either eye as a result of non-age related macular degeneration causes (including pathlogic myopia, ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, or multifocal choroiditis) as assessed by FA and confirmed by the CRC
25. Presence or history of scleromalacia in either eye
26. Active or recent (within 28 days before screening) intraocular or periocular inflammation or infection in either eye, including but not limited to conjunctivitis, keratitis, scleritis, or endophthalmitis
27. History of idiopathic or autoimmune-associated uveitis in either eye
Considerations for systemic treatments and general conditions
28. Any systemic treatment to treat nAMD within 30 days before screening; such treatment or therapy will not be allowed during the study period. However, dietary supplements, vitamins, or minerals will be allowed during study
29. Any previous systemic anti-VEGF therapy within 180 days before screening
30. Use of systemic corticosteroids (except short-term (<14 consecutive days) oral corticosteroids; or inhaled, nasal, intra articular, and dermal corticosteroids) within 180 days before screening or a plan for the use of systemic corticosteroids during the course of the study
31. Use of medications known to be toxic to the lens, retina, or optic nerve at screening (such medications will not be allowed during the study period)
32. Reasonable suspicion of a disease or condition that might render the subject at high risk of treatment complications or affect the interpretation of study results (as judged by the investigator), such as uncontrolled hypertension (systolic blood pressure >160 mm Hg or diastolic blood pressure >100 mm Hg at screening), stroke, or myocardial infarction within 180 days before screening
33. Current treatment for active systemic infection
34. Contraindication for Eylea as defined in the package insert (hypersensitivity to aflibercept or any of its excipients, active or suspected ocular or periocular infection, or active severe intraocular inflammation) or known allergic reactions to any ingredients of ALT-L9
35. History of allergy to fluorescein, povidone iodine, or any other study medications (including anesthetic eyedrops, etc) that cannot be replaced by an equivalent medication
36. Participation in another interventional clinical trial for nAMD in either eye within 90 days before screening or any previous participation in a clinical trial of systemic antiangiogenic drugs with receipt of a previous study drug within 180 days before screening or 5 times the half-life of the study drug used, whichever is longer
37. Concurrent participation in any other interventional clinical trial
38. Females who are pregnant, breastfeeding, or of childbearing potential unwilling to practice adequate contraception throughout the study
39. PK subgroup only: contraindication for additional and repeated blood samplings (as judged by the investigator)

Related Information

• Primary Sponsor: Kobayashi Takeshi