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A Phase III Randomized, Double-Masked, Parallel Group, Multicenter Study to Compare the Efficacy, Safety, Tolerability, Pharmacokinetics, and Immunogenicity between SCD411 and Eylea in Subjects with Neovascular
Age-related Macular Degeneration

A Phase III Study of SCD411 in Subjects with Neovascular Age-related Macular Degeneration

60

The mean (SD: standard deviation) age of the subjects was 73.5 (8.27) years. Most subjects were >= 65 years of age. There were 277 males (48.3%) and 296 females (51.7%) in the study; all females were of non-childbearing potential. Majority of subjects were of White (382 subjects [66.7%]) or Asian (187 subjects [32.6%]) race and not Hispanic or Latino (554 subjects [96.7%]) ethnicity. The mean (SD) weight of the subjects was 72.32 (14.757) kg and BMI was 26.67 (4.424) kg/m2. Overall, the mean (SD) Best-corrected visual acuity (BCVA) score was 59.3 (10.69) letters; Central retinal thickness (CRT) was 490.1 (172.65) um, total lesion area was 5.5069 (4.72374) mm2; Choroidal neovascularization (CNV) area was 4.5685 (4.23108) mm2; leakage area was 6.6884 (4.77559) mm2; and intraocular pressure (IOP) was 15.2 (2.87) mmHg in the study eye. Anterior chamber flare, anterior chamber cells, and vitreous cells in the study eye were of grade zero in all the subjects. The vitreous haze was also grade zero in 567 subjects (99.0%) and grade 1 in 6 subjects (1.0%). The overall slit lamp, vitreous, retina, and optic nerve assessments in the study eye were normal in most subjects. In line with the study indication, the overall macula assessment in the study eye was reported as abnormal in most subjects, with clinically significant (CS) abnormalities reported in 346 subjects (60.4%). All subjects (573 [100%]) had at least one ocular medical history in the study eye. The most common were eye disorders including neovascular Age-related macular degeneration (AMD) reported in 562 subjects (98.1%) and cataract reported in 257 subjects (44.9%). Ocular medical history in the fellow eye was reported in 442 subjects (77.1%). The most common were eye disorders including cataract reported in 250 subjects (43.6%) and dry AMD reported in 209 subjects (36.5%). Non-ocular medical history was reported in 520 subjects (90.8%), most commonly in the system organ classes (SOCs) of vascular disorders (366 subjects [63.9%]), metabolism and nutrition disorders (297 subjects [51.8%]), musculoskeletal and connective tissue disorders (194 subjects [33.9%]), and gastrointestinal disorders (152 subjects [26.5%]). Most common medical histories (reported in >=10.0% of subjects) by preferred term (PT) included hypertension (339 subjects [59.2%]), hyperlipidemia (110 subjects [19.2%]), hypercholesterolemia (90 subjects [15.7%]), type 2 diabetes mellitus (79 subjects [13.8%]), osteoarthritis (74 subjects [12.9%]), and benign prostatic hyperplasia (73 subjects [12.7%]).

A total of 914 subjects were assessed for eligibility across 132 sites in 14 countries. A total of 576 subjects were randomly assigned to 1 of 2 treatment groups: 288 subjects each to the SCD411 group and Eylea group. A total of 515 subjects (89.4%) had completed the study treatment: 259 subjects (89.9%) in the SCD411 group and 256 subjects (88.9%) in the Eylea group, and 61 subjects (10.6%) had discontinued the study treatment: 29 subjects (10.1%) in the SCD411 group and 32 subjects (11.1%) in the Eylea group. The most common reasons for discontinuing study treatment across treatment groups were adverse event (AE) (14 subjects [23.0%]), withdrawal of consent by the subject (13 subjects [21.3%]), and other (10 subjects [16.4%]). A total of 566 subjects (98.3%) had completed Week 8 of the study: 281 subjects (97.6%) in the SCD411 group and 285 subjects (99.0%) in the Eylea group. A total of 522 subjects (90.6%) had completed the study: 261 subjects (90.6%) each in the SCD411 group and Eylea group. A total of 54 subjects (9.4%) had prematurely discontinued the study: 27 subjects (9.4%) each in the SCD411 and Eylea groups. The most common reasons for discontinuing the study across treatment groups were withdrawal of consent by the subject (14 subjects [25.9%]), AE (9 subjects [16.7%]), and other (9 subjects [16.7%]). <Subject Disposition> Number of patients whose eligibility has been reviewed: Japan 87 (Global 827) Number of subjects who have been confirmed as eligible: Japan 60 (Global 516) Number of enrolled subjects, number of subjects who have completed follow-up: Japan 56 (Global 466) Number of subjects who have been analyzed: Japan 60 (Global 513)

1. Treatment-Emergent Adverse Events (TEAE) of the Study Eye Overall, TEAEs of the study eye were reported in 140 subjects (24.4%). There were no ocular TEAE-related deaths. Treatment-emergent AEs related to study drug and injection procedure were reported in 27 subjects (4.7%) and 39 subjects (6.8%), respectively. Non fatal ocular serious TEAEs of the study eye were reported in 8 subjects (1.4%), and serious TEAEs in 2 subjects (0.3%) each were related to the study drug and injection procedure. None of the TEAEs in the study eye led to dose interruption. Treatment-emergent AEs of the study eye leading to treatment discontinuation were reported in 9 subjects (1.6%) and leading to study discontinuation were reported in 4 subjects (0.7%). Most TEAEs of the study eye were mild or moderate in intensity and severe TEAEs were reported in 4 subjects (0.7%). 2. TEAE of the Fellow Eye Overall, TEAEs of the fellow eye were reported in 102 subjects (17.8%). In the fellow eye, there were no fatal TEAEs or TEAEs that led to treatment or study discontinuation. Treatment emergent AEs related to study drug and injection procedure were reported in 1 subject (0.2%) and 3 subjects (0.5%), respectively. A non-fatal ocular serious TEAE of the fellow eye was reported in 1 subject (0.2%). Treatment emergent AE of the fellow eye leading to dose interruption were reported in 1 subject (0.2%). Almost all TEAEs of the fellow eye were mild or moderate in intensity and severe TEAEs were reported in 2 subjects (0.3%). Non-Ocular TEAE Overall, non-ocular TEAEs were reported in 258 subjects (45.0%). Treatment-emergent AEs related to study drug and injection procedure were reported in 2 subjects (0.3%) and 1 subject (0.2%), respectively. There were no non-ocular TEAE-related deaths. Non-fatal non-ocular serious TEAEs were reported in 54 subjects (9.4%), and serious TEAEs in 2 subjects (0.3%) were related to the study drug. Non-ocular TEAEs leading to dose interruption were reported in 8 subjects (1.4%). Non-ocular TEAEs leading to treatment discontinuation were reported in 7 subjects (1.2%) and leading to study discontinuation were reported in 3 subjects (0.5%). Most non-ocular TEAEs were mild in intensity and severe TEAEs were reported in 40 subjects (7.0%).

Primary Endpoint: At Week 8, the LS (least square) mean difference between the treatment groups (SCD411-Eylea) for estimated mean change from baseline in BCVA score was - 0.4 letters with 90% CI (confidence interval) = - 1.6 to 0.9 and 95% CI = - 1.8 to 1.1. Secondary Endpoint: Change from Baseline in BCVA Score for Study Eye at Week 52: At Week 52, for the full analysis set (FAS), the LS mean difference between the treatment groups (SCD411 Eylea) for estimated mean change from baseline in BCVA score was 1.3 letters with 90% CI = - 0.4 to 2.9 and 95% CI = - 0.7 to 3.2. Mean change from baseline in CRT at Week 8 and Week 52: The LS mean difference between the treatment groups (SCD411-Eylea) for estimated mean change from baseline in CRT at Week 8 was 0.5 um (90% CI = - 11.8 to 12.9 and 95% CI = - 14.2 to 15.2) and at Week 52 was - 10.7 um (90% CI = - 22.8 to 1.5 and 95% CI = - 25.1 to 3.8). Mean change from baseline in CNV at Week 8 and Week 52: The LS mean difference between the treatment groups (SCD411-Eylea) for estimated mean change from baseline in CNV area at Week 8 was 0.2146 mm2 (90% CI = - 0.1152 to 0.5444 and 95% CI = - 0.1785 to 0.6078) and at Week 52 was - 0.2837 mm2 (90% CI = - 0.6593 to 0.0919 and 95% CI = - 0.7313 to 0.1639).

- SCD411 is efficacious, equivalent to Eylea with respect to the change from baseline in BCVA score for study eye at Week 8. - SCD411 is well-tolerated with a favorable safety profile that is comparable with Eylea.

Oct. 06, 2023

https://clinicaltrials.gov/ct2/show/NCT04480463

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2041210008

Sakamoto Taiji

Kagoshima University Hospital

8-35-1 Sakuragaoka, Kagoshima-shi, Kagoshima

Sayaka.Kakoi@ppd.com

Youngmi Park

PPDSNBL K.K.

3-3-23 Nakanoshima, Kita-ku, Osaka-shi, Osaka

+81-6-4560-6800

Sayaka.Kakoi@ppd.com

Complete

Nov. 27, 2020

Interventional

randomized controlled trial

double blind

active control

parallel assignment

treatment purpose

- Age >=50 years.
- Active choroidal subfoveal, juxtafoveal, or extrafoveal neovascularization lesions secondary to AMD evidenced by fluorescein angiography (FA) in the study eye at screening and confirmed by the central reading center.

- Any prior ocular (in the study eye and fellow eye) or systemic treatment or surgery for neovascular AMD except dietary supplements or vitamins
- Any prior or concomitant therapy with another investigational agent to treat neovascular AMD in the study eye, except dietary supplements or vitamins

Both

Neovascular Age-related Macular Degeneration

Biological:SCD411 or Eylea (aflibercept), Dosage and administration are subject to those of Eylea, which has already been approved in Japan.

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.

- 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 choroidal neovascularization (CNV)
- To compare the immunogenicity of SCD411 and aflibercept by presenting information of the development of anti-SCD411 antibodies.

+81-52-691-7151

June. 29, 2020

US/Hungary/The Republic of Korea/Australia/Israel/India/Poland/Russia/Slovakia/Bulgaria/Spain/Czech/Spain