Neovascular Age-related Macular Degeneration, Wet Age-related Macular Degeneration
Conditions
Keywords
Age-related macular degeneration, AMD, Neovascular, Exudative
Brief summary
Age-related macular degeneration (AMD) is a leading cause of vision loss in adults. Abnormal blood vessels grow under the macula at the back of the eye, and also leak blood and fluid, which damages and scars the macula, affecting vision. The current standard of care for patients with neovascular (exudative / wet) AMD is anti-vascular endothelial growth factor (anti-VEGF) therapy, which prevents or slows down the growth of the abnormal blood vessels. SCD411 is being developed as a biosimilar to the reference product Eylea® (aflibercept), an anti-VEGF drug. The study aims to prove equivalence of SCD411 to Eylea in adults with wet AMD, and will look at safety, tolerance, effectiveness, immune response and the movement of the drug through the body.
Interventions
DRUGSCD411
IVT (intravitreal) injection
DRUGAflibercept
IVT injection
Sponsors
Sam Chun Dang Pharm. Co. Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Only the unmasked investigator involved in performing the IVT injections will be unmasked to study treatment. These individuals are not allowed to discuss treatment and/or subject outcome with masked study staff, including the evaluating investigator.
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provides written informed consent. * Clinical diagnosis of wet (neovascular) age-related macular degeneration (AMD). * BCVA (best corrected visual acuity) letter score of 73 to 35 at screening and prior to randomization. In addition, fellow eye should not be less than 35 letter score using the ETDRS chart or 2702 series number chart. * Women of child-bearing potential with negative serum pregnancy test at screening must agree to use protocol-defined methods of contraception throughout study until 3 months after last injection of aflibercept/SCD411. * Males with female partners of child-bearing potential must agree to use protocol-defined methods of contraception and refrain from donating sperm throughout study until 3 months after last injection of aflibercept/SCD411.
Exclusion criteria
* Any prior eye (study eye and fellow eye) or systemic treatment or surgery for neovascular AMD, except dietary supplements or vitamins. * Any prior or current treatment with another investigational agent to great neovascular AMD in the study eye, except dietary supplements or vitamins. * Fellow eye shows signed of AMD that may need treatment during study period. * Any prior treatment with anti-VEGF agents in both eyes. * Total lesion size \>30.5 mm2, Blood, scars, atrophy, fibrosis, and neovascularization, based on assessment at screening. * Central retina thickness of \<300 µm in the study eye. * Subretinal hemorrhage that is either 50% or more of the total lesion area. * Scar or fibrosis making up \>50% of the total lesion. * Scar, fibrosis, or atrophy involving the center of the fovea in the study eye. * Presence of retinal pigment epithelial tears or rips involving the macular in the study eye. * Cataract in the study eye that have Lens Opacity Classification System II (LOCS II) grade IV cataract in the study eye or in the Investigator's opinion, interferes with visualization of retina or retinal imaging. * Inflammation outside the eyeball in either eye, or within the eyeball of the study eye. * History of any vitreous hemorrhage in the study eye. * History or clinical evidence of diabetic retinopathy, diabetic macular edema, or any other vascular disease. * History of, treatment or surgery for detached retina. * History of uncomplicated surgery within the eyeball or around the study eye, except lid surgery. * Absence of lens in study eye. * Uncontrolled hypertension, defined as systolic blood pressure (BP) \>160 mmHg or diastolic BP \>100 mmHg under appropriate antihypertensive treatment. * Hypersensitivity to aflibercept or medications used in the study (fluorescein, mydriatic eye drops, etc.). * Pregnancy or lactation at Screening or at baseline for women of child-bearing potential. * History of blood clotting events. * History or evidence of cardiac conditions, or inability to perform any physical activity without discomfort; ventricular arrhythmia; and atrial fibrillation. * History of laser therapy in the macular region. * Any prior or current treatment with corticosteroids inside or immediately around the study eye. * Any prior or current treatment involving the macula with photodynamic therapy (PDT) with verteporfin, transpupillary thermotherapy, radiation therapy, or retinal laser treatment in the study eye. * Any prior or current treatment with pan-retinal photocoagulation. * Any prior or current treatment with ethambutol; deferoxamine and topiramate; tamoxifen, hydroxychloroquine, chloroquine, or vigabatrin; and amiodarone. * Any investigational product for the treatment of eye conditions and systemic conditions, 30 days or 5 half-lives (whichever is longer), prior to randomization, and throughout the study, except dietary supplements or vitamins. * Intraocular pressure ≥25 mmHg in spite of anti-glaucoma treatment. * Any prior or ongoing systemic medical condition (including but not limited to infectious, inflammatory, psychiatric, neurological, renal, hepatic, respiratory conditions or malignancies) or clinically significant screening laboratory value that in the opinion of the investigator may present a safety risk, interfere with study compliance and follow-up, or confound data interpretation throughout the study period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in BCVA (Best Corrected Visual Acuity) | Baseline to Week 8 | Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) letters score or 2702 charts |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in BCVA (Best Corrected Visual Acuity) | Baseline to Week 52 | Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) letters score or 2702 charts |
| Percentage of Subjects With Anti-SCD411 Antibodies | Baseline, Weeks 4, 8, 20, 36 and 52 | Assessed by blood samples |
Countries
Australia, Bulgaria, Czechia, Hungary, India, Israel, Japan, Latvia, Poland, Russia, Slovakia, South Korea, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SCD411 SCD411: IVT (intravitreal) injection | 287 |
| Aflibercept Aflibercept: IVT injection | 286 |
| Total | 573 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | A decrease in BCVA of ≥30 letters compared with the last assessment of VA | 1 | 0 |
| Overall Study | Adverse Event | 6 | 8 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Decision by the sponsor or administrative decision for a reason other than that of an AE | 2 | 3 |
| Overall Study | Lost to Follow-up | 3 | 2 |
| Overall Study | Other | 6 | 4 |
| Overall Study | Physician Decision | 2 | 5 |
| Overall Study | Protocol Violation | 2 | 1 |
| Overall Study | Subject missed any of first 2 doses (IVT I injection of IP at Day 1 or Week 4) after randomization | 0 | 1 |
| Overall Study | Subretinal hemorrhage involving center of fovea or, size of hemorrhage was ≥50% of total lesion area | 1 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 7 |
Baseline characteristics
| Characteristic | Total | Aflibercept | SCD411 |
|---|---|---|---|
| Age, Continuous | 73.5 years STANDARD_DEVIATION 8.27 | 73.6 years STANDARD_DEVIATION 8.55 | 73.5 years STANDARD_DEVIATION 8 |
| Age, Customized 50 to less than 65 years | 73 Participants | 40 Participants | 33 Participants |
| Age, Customized 65 to less than 75 years | 250 Participants | 119 Participants | 131 Participants |
| Age, Customized Greater than or equal to 75 years | 250 Participants | 127 Participants | 123 Participants |
| Best Corrected Visual Acuity (BCVA) | 59.3 Letters correctly read STANDARD_DEVIATION 10.69 | 59.9 Letters correctly read STANDARD_DEVIATION 10.6 | 58.6 Letters correctly read STANDARD_DEVIATION 10.75 |
| BMI | 26.67 kg/m^2 STANDARD_DEVIATION 4.424 | 26.53 kg/m^2 STANDARD_DEVIATION 4.154 | 26.81 kg/m^2 STANDARD_DEVIATION 4.682 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 19 Participants | 10 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 554 Participants | 276 Participants | 278 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 164.33 centimeters STANDARD_DEVIATION 9.045 | 164.64 centimeters STANDARD_DEVIATION 8.976 | 164.02 centimeters STANDARD_DEVIATION 9.117 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 187 Participants | 90 Participants | 97 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 382 Participants | 194 Participants | 188 Participants |
| Region of Enrollment Australia | 13 participants | 6 participants | 7 participants |
| Region of Enrollment Bulgaria | 4 participants | 2 participants | 2 participants |
| Region of Enrollment Czechia | 6 participants | 3 participants | 3 participants |
| Region of Enrollment Hungary | 39 participants | 17 participants | 22 participants |
| Region of Enrollment India | 9 participants | 1 participants | 8 participants |
| Region of Enrollment Israel | 84 participants | 42 participants | 42 participants |
| Region of Enrollment Japan | 60 participants | 30 participants | 30 participants |
| Region of Enrollment Latvia | 23 participants | 13 participants | 10 participants |
| Region of Enrollment Poland | 87 participants | 50 participants | 37 participants |
| Region of Enrollment Russia | 22 participants | 10 participants | 12 participants |
| Region of Enrollment Slovakia | 29 participants | 13 participants | 16 participants |
| Region of Enrollment South Korea | 118 participants | 59 participants | 59 participants |
| Region of Enrollment Spain | 44 participants | 24 participants | 20 participants |
| Region of Enrollment United States | 35 participants | 16 participants | 19 participants |
| Sex: Female, Male Female | 296 Participants | 147 Participants | 149 Participants |
| Sex: Female, Male Male | 277 Participants | 139 Participants | 138 Participants |
| Weight | 72.32 kilograms STANDARD_DEVIATION 14.757 | 72.26 kilograms STANDARD_DEVIATION 12.28 | 72.39 kilograms STANDARD_DEVIATION 15.244 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 287 | 1 / 286 |
| other Total, other adverse events | 128 / 287 | 121 / 286 |
| serious Total, serious adverse events | 32 / 287 | 30 / 286 |
Outcome results
Primary
Change From Baseline in BCVA (Best Corrected Visual Acuity)
Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) letters score or 2702 charts
Time frame: Baseline to Week 8
Population: The Full Analysis Set included all randomized subjects who received at least 1 injection of the study drug.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| SCD411 | Change From Baseline in BCVA (Best Corrected Visual Acuity) | 5.5 Letters correctly read |
| Aflibercept | Change From Baseline in BCVA (Best Corrected Visual Acuity) | 5.9 Letters correctly read |
Secondary
Change From Baseline in BCVA (Best Corrected Visual Acuity)
Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) letters score or 2702 charts
Time frame: Baseline to Week 52
Population: The Full Analysis Set included all randomized subjects who received at least 1 injection of the study drug.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| SCD411 | Change From Baseline in BCVA (Best Corrected Visual Acuity) | 9.0 Letters correctly read |
| Aflibercept | Change From Baseline in BCVA (Best Corrected Visual Acuity) | 7.7 Letters correctly read |
Secondary
Percentage of Subjects With Anti-SCD411 Antibodies
Assessed by blood samples
Time frame: Baseline, Weeks 4, 8, 20, 36 and 52
Population: The Safety Set included all subjects who received at least 1 injection of the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SCD411 | Percentage of Subjects With Anti-SCD411 Antibodies | Baseline : Positive | 7.1 Percentage of participants |
| SCD411 | Percentage of Subjects With Anti-SCD411 Antibodies | Baseline : Negative | 92.9 Percentage of participants |
| SCD411 | Percentage of Subjects With Anti-SCD411 Antibodies | Week 4 : Positive | 29.4 Percentage of participants |
| SCD411 | Percentage of Subjects With Anti-SCD411 Antibodies | Week 4 : Negative | 70.6 Percentage of participants |
| SCD411 | Percentage of Subjects With Anti-SCD411 Antibodies | Week 8 : Positive | 40.0 Percentage of participants |
| SCD411 | Percentage of Subjects With Anti-SCD411 Antibodies | Week 8 : Negative | 60.0 Percentage of participants |
| SCD411 | Percentage of Subjects With Anti-SCD411 Antibodies | Week 20 : Positive | 39.6 Percentage of participants |
| SCD411 | Percentage of Subjects With Anti-SCD411 Antibodies | Week 20 : Negative | 60.4 Percentage of participants |
| SCD411 | Percentage of Subjects With Anti-SCD411 Antibodies | Week 36 : Positive | 22.9 Percentage of participants |
| SCD411 | Percentage of Subjects With Anti-SCD411 Antibodies | Week 36 : Negative | 77.1 Percentage of participants |
| SCD411 | Percentage of Subjects With Anti-SCD411 Antibodies | Week 52 : Positive | 20.2 Percentage of participants |
| SCD411 | Percentage of Subjects With Anti-SCD411 Antibodies | Week 52 : Negative | 79.8 Percentage of participants |