E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Neovascular Age-related Macular Degeneration |
|
E.1.1.1 | Medical condition in easily understood language |
Age-related macular degeneration (AMD) is a disease that impacts the central area of the retina in the eye, called the macula. AMD is a leading cause of blindness |
|
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 |
|
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 prove the equivalence of SCD411 as compared to Eylea (aflibercept) in best corrected visual acuity (BCVA) after 8 weeks of treatment among subjects with wet AMD |
|
E.2.2 | Secondary objectives of the trial |
• To compare the safety and tolerability of SCD411 and aflibercept
• To compare the efficacy of SCD411 and aflibercept after 8 weeks and 52 weeks of treatment demonstrated by BCVA, central retinal thickness (CRT), and CNV
• To compare the immunogenicity of SCD411 and aflibercept by presenting information of the development of anti-SCD411 antibodies |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Capable of understanding the written informed consent, provides signed and witnessed written informed consent, and agrees to comply with protocol requirements.
2. Age ≥50 years.
3. Active choroidal neovascularization lesions secondary to AMD evidenced by fluorescein angiography (FA) in the study eye at screening and confirmed by the central reading center.
4. The BCVA letter score of 73 to 35 using original series ETDRS charts or 2702 series number charts in the study eye at screening and at Week 0 (Day 1) prior to randomization. In addition, fellow eye should not be less than 35 letter score using the ETDRS chart or 2702 series number chart
5. Women of child-bearing potential with a negative serum pregnancy test at screening must agree to use protocol-defined methods of contraception throughout the study until 3 months after the last injection of aflibercept/SCD411 (Section 4.1.3 and Section 4.1.4).
6. Males with female partners of child-bearing potential must agree to use protocol-defined methods of contraception and agree to refrain from donating sperm throughout the study until 3 months after the last injection of aflibercept/SCD411. |
|
E.4 | Principal exclusion criteria |
1. Any prior ocular (in the study eye and fellow eye) or systemic treatment or surgery for neovascular AMD except dietary supplements or vitamins
2. Any prior or concomitant therapy with another investigational agent to treat neovascular AMD in the study eye, except dietary supplements or vitamins
3. Fellow eye shows signs of AMD that, in investigator’s medical opinion, may need any treatment during study period
4. Any prior treatment with anti-VEGF agents in the both eyes
5. Total lesion size >30.5 mm2, including blood, scars, atrophy, fibrosis, and neovascularization as assessed by FA in the study eye and confirmed by the central reading center
6. Central retina thickness of <300 μm in the study eye and confirmed by the central reading center
7. Subretinal hemorrhage that is either 50% or more of the total lesion area, or if the blood is under the fovea and is 1 or more disc areas in size in the study eye and confirmed by the central reading center.
8. Scar or fibrosis, making up >50% of the total lesion in the study eye and confirmed by the central reading center
9. Scar, fibrosis, or atrophy involving the center of the fovea in the study eye and confirmed by the central reading center
10. Presence of retinal pigment epithelial tears or rips involving the macula in the study eye and confirmed by the central reading center
11. Lens Opacity Classification System II grade IV cataract in the study eye, or other significant cataract in the study eye that in the Investigator’s opinion interferes with visualization of retina or interferes with retinal imaging
12. Active extraocular inflammation in either eye or intraocular inflammation in study eye
13. History of any vitreous hemorrhage in the study eye within 4 wks prior to the Screening Visit
14. Presence of other causes of CNV in the study eye as confirmed by central reading center
15. History or clinical evidence of diabetic retinopathy, DME, or any other vascular disease affecting the retina, other than AMD, in either eye
16. Prior vitrectomy in the study eye
17. History of retinal detachment, treatment, or surgery for retinal detachment in the study eye
18. History of macular hole of Stage 2 and above in the study eye as confirmed by central reading center
19. History of uncomplicated intraocular or periocular surgery within 3 months of Day 1 on the study eye, except lid surgery, which may not have taken place within 1 month of Day 1
20. Presence of aphakia in the study eye
21. History of glaucoma-filtering surgery within 3 months of Day 1 in the study eye. Antiglaucoma laser surgeries will not be considered exclusionary.
22. History of corneal transplant in the study eye
23. History or evidence of any other clinically significant disorder, condition or disease (eg, co-existence of RVO, radiation retinopathy, diabetic retinopathy, glaucoma under treatment) in the study eye that, in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, procedure or complication
24. Uncontrolled hypertension defined as systolic blood pressure (BP) >180 mmHg or diastolic BP >100 mmHg under appropriate antihypertensive treatment
25. Hypersensitivity to aflibercept or medications used in this study
26. Pregnancy or lactation at the Screening Visit and/or at baseline for women of child-bearing potential
27. Any contraindication to IVT injection according to the investigator’s clinical judgment
28. History of thrombotic events
29. History or evidence of cardiac conditions including congestive cardiac failure leading to marked limitation on physical activity, or inability to perform any physical activity without discomfort, ventricular arrhythmia requiring ongoing treatment, and atrial fibrillation
30. History of laser therapy in the macular region in the study eye
31. Any prior or concomitant treatment with IVT corticosteroids injection, IVT corticosteroid implant, subtenon corticosteroids, or peribulbar corticosteroids in the study eye 6 months before the Screening Visit
32. Any prior or concomitant treatment involving the macula with photodynamic therapy (PDT) with verteporfin, transpupillary thermotherapy, radiation therapy, or retinal laser treatment (eg, focal laser photocoagulation) in the study eye
33. Any prior or concomitant treatment with pan-retinal photocoagulation 90 days in the study eye before the Screening Visit
34. Any concomitant or prior treatment with ethambutol (2 wks prior to randomization); deferoxamine and topiramate (4 wks prior to randomization); tamoxifen, hydroxychloroquine, chloroquine, or vigabatrin (8 wks prior to randomization), and amiodarone (12 wks prior to randomization)
35. Any investigational product for the treatment of ocular conditions (in either eye) and systemic conditions 30 days or 5 half-lives (whichever is longer), prior to randomization, and throughout the study, except dietary supplements or vitamins.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint:
• Change from baseline in BCVA as measured by ETDRS letters
score or 2702 charts. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Secondary endpoints:
• Change from baseline in best corrected visual acuity (BCVA) as measured by Early
Treatment Diabetic Retinopathy Study (ETDRS) letter score or 2702 charts at Week 52
• Change from baseline in CRT at Week 8 as assessed by optical
coherence tomography (OCT)
• Change from baseline in central retinal thickness (CRT) at Week 52 as assessed by OCT
• Change from baseline in choroidal
neovascularization (CNV) area at Week 8
• Change from baseline in CNV area at Week 52
• Percentage of subjects who gain at least 15 letters in BCVA as measured by ETDRS letter score or 2702 charts compared with
baseline at Week 8
• Percentage of subjects who gain at least 15 letters in BCVA as measured by ETDRS letter score or 2702 charts compared with
baseline at Week 52. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | Yes |
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 |
|
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 55 |
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 |
Australia |
Bulgaria |
Czech Republic |
Hungary |
India |
Israel |
Italy |
Japan |
Korea, Republic of |
Latvia |
Poland |
Russian Federation |
Slovakia |
Spain |
United States |
|
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
|
The end of the study is defined as the date of the last visit of the
last subject in the study. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 24 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 24 |