E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Neovascular Age-related Macular Degeneration |
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E.1.1.1 | Medical condition in easily understood language |
Degenerative retinal disease characterized by damage to the macula, swelling and haemorrhages. Central vision can be blurred, decreased or even lost. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Eye Diseases [C11] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10071129 |
E.1.2 | Term | Neovascular age-related macular degeneration |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate the equivalence of efficacy of SB11 to Lucentis® in subjects with neovascular age-related macular degeneration |
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E.2.2 | Secondary objectives of the trial |
•To evaluate the safety of SB11 and Lucentis®
•To evaluate the immunogenicity of SB11 and Lucentis®
•To evaluate the systemic exposure of SB11 and Lucentis® in subjects participating in pharmacokinetics (PK) evaluation
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacokinetics Analyses: For safety purpose, PK sampling will be collected in approximately 40 subjects participating in PK evaluation (20 subjects per treatment group). Formal PK analysis will not be performed. The systemic exposure will be summarised descriptively by treatment group and visit.
The pharmacokinetic endpoints are:
•Blood sampling for PK will be collected in approximately 40 subjects participating in PK evaluation (20 subjects per treatment group).
•Systemic exposure measured pre-dose (Ctrough) and 24 to 72 hours post-dose (close to Cmax) |
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E.3 | Principal inclusion criteria |
1.Age ≥ 50 years at Screening
2.Newly diagnosed, *active subfoveal Choroidal Neovascularisation (CNV) lesion secondary to AMD in the study eye
* Active CNV indicates presence of leakage and intra- or sub-retinal fluid which should be confirmed by central reading centre during Screening
3.The area of CNV must occupy at least 50% of total lesion in the study eye (confirmed by central reading centre during Screening)
4.Total lesion area ≤ 9.0 Disc Areas (DA) in size (including blood, scars and neovascularisation) in the study eye (confirmed by central reading centre during Screening)
5.Best Corrected Visual Acuity (BCVA) of 20/40 to 20/200 (letter score of 73 to 34) using original series Early Treatment Diabetic Retinopathy Study (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 (e.g., permanently sterilised, postmenopausal [defined as 12 months with no menses without an alternative medical cause prior to Screening]), 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 (e.g., established use of oral, injected, intravaginal, transdermal or implanted hormonal contraceptive, placement of an intrauterine device or intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner, physical barrier, sexual abstinence) from Screening until 3 months after the last ITV injection of IP
7.Written informed consent form must be obtained from the subject prior to any study related procedure (If the subject is legal blindness or illiterate, an impartial witness should be present during the entire informed consent discussion)
8.Willingness and ability to undertake all scheduled visits and assessments
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E.4 | Principal exclusion criteria |
1.Sub- or intra-retinal haemorrhage that comprises more than 50% of the entire lesion in the study eye, or presence of subfoveal blood equal to or more than one DA in size (confirmed by central reading centre during Screening)
2.Scar, fibrosis or atrophy involving the centre of the fovea in the study eye (confirmed by central reading centre during Screening)
3.Presence of CNV in either eye due to other causes, such as ocular histoplasmosis, trauma, multifocal choroiditis, angioid streaks, history of choroidal rupture or Pathologic Myopia (PM) (confirmed by central reading centre during Screening)
4.Presence of retinal pigment epithelial tears or rips involving the macula in the study eye as assessed by FA (confirmed by central reading centre during Screening)
5.Presence of macular hole at any stage in the study eye (confirmed by central reading centre during Screening)
6.Any concurrent macular abnormality other than AMD in the study eye which, could affect the efficacy of IP including but not limited to epiretinal membrane, macular telangiectasia, retinal vascular abnormality, etc. (confirmed by central reading centre during Screening)
7.History of vitrectomy surgery in the study eye
8.History of trabeculectomy or other filtration surgery in the study eye
9.History of submacular surgery or other surgical intervention for AMD in the study eye
10.Any other intraocular surgery (including cataract surgery) or periocular surgery in the study eye within 90 days prior to randomisation, except for lid surgery, which may not have taken place within 30 days prior to randomisation
11.Any previous ITV anti-Vascular Endothelial Growth Factor (anti-VEGF) treatment (e.g., bevacizumab, aflibercept, ranibizumab) to treat neovascular AMD in either eye
12.Any previous systemic anti-VEGF treatment, within 90 days prior to randomisation, and such treatment will not be allowed during the study period
13.Any systemic treatment or therapy (including prescribed herbal medication) to treat neovascular AMD within 30 days prior to randomisation, and such treatment or therapy will not be allowed during the study period. However, dietary supplements, vitamins or mineral will be allowed
14.Any intravitreal injection of corticosteroid (e.g., triamcinolone acetonide) or intravitreal corticosteroid implant in the study eye within 180 days prior to randomisation, and such treatment will not be allowed during the study period
15.Topical ocular corticosteroids administered for ≥ 30 consecutive days in the study eye within 90 days prior to randomisation
16.Spherical equivalent of the refractive error in the study eye demonstrating more than 8 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 must not exceed 8 diopters of myopia
17.Aphakia or absence of the posterior capsule in the study eye
18.Presence of scleromalacia in either eye
19.Current vitreous haemorrhage in the study eye
20.Active or recent (within 28 days prior to randomisation) intraocular, extraocular and periocular inflammation or infection in either eye
21.History of idiopathic or autoimmune uveitis in either eye
22.History of retinal detachment in the study eye
23.History of full-thickness macular hole in the study eye
24.History of corneal transplantion surgery in the study eye
25.Presence of advanced glaucoma or optic neuropathy that affect or threaten the central visual field in the study eye
26.Uncontrolled ocular hypertension (defined as intraocular pressure ≥ 25 mmHg despite treatment with anti-glaucoma medication) in the study eye
27.History of allergy to the fluorescein sodium for injection in angiography
28.Previous participation in clinical studies of ocular investigational products to treat neovascular AMD
29.Previous participation in any studies of ocular or systemic investigational products to treat ocular or systemic disease within 90 days prior to randomisation
30.History or clinical evidence of diabetic retinopathy (except for mild non-proliferative diabetic retinopathy), or diabetic macular oedema in either eye
31.Any concurrent ocular condition in the study eye which, in the opinion of the Investigator, could either increase the risk to the subject safety or which otherwise may interfere with evaluation of efficacy or safety.
32.Stroke, transient ischemic attacks, or myocardial infarction within 90 days prior to randomisation 33.History of recurrent significant or active infections
34.Known allergic reactions and/or hypersensitivity to ranibizumab or to any ingredients of SB11
35.Prior treatment involving macula with photodynamic therapy with verteporfin, transpupillary thermotherapy, radiation therapy, or retinal laser treatment
36.Prior treatment with pan-retinal photocoagulation in the study eye
37.Current use of systemic medications known to be toxic to the lens, retina or optic nerve |
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E.5 End points |
E.5.1 | Primary end point(s) |
For European Medicines Agency (EMA) or other regulatory agency submissions for those who are in favour of the anatomical parameter, the primary endpoint is:
•Change from baseline in Central Subfield Thickness (CST) at Week 4 (based on assessment by central reading centre)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
•Change from baseline in BCVA over time up to Week 24 and Week 52
•Proportion of subjects who lost fewer than 15 letters in BCVA compared to baseline at Week 24 and Week 52
•Proportion of subjects who gained 15 letters or more in BCVA compared to baseline at Week 24 and Week 52
•Change from baseline in CST and Central Retinal Lesion Thickness (CRLT) at Week 24 and Week 52 (based on assessment by central reading centre)
•Change from baseline in total CNV size at Week 24 and Week 52 (based on assessment by central reading centre)
•Proportion of subjects with active CNV leakage at Week 24 and Week 52 (based on assessment by central reading centre)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline, week 24, week 52
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 39 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Czech Republic |
Germany |
Hungary |
India |
Korea, Republic of |
Poland |
Russian Federation |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 17 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 17 |