Neovascular (Wet) Age-related Macular Degeneration (AMD)
Conditions
Brief summary
The purpose of this study is to compare the efficacy and safety of ABP 938 versus Aflibercept (Eylea®) in the treatment of neovascular age-related macular degeneration. Subjects will be randomized in a masked 1:1 ratio to receive 2 mg (0.05 mL) of either ABP 938 (Treatment Group A) or aflibercept (Treatment Group B) administered by intravitreal (IVT) injection.
Detailed description
Approximately 566 subjects will be randomized in approximately 126 global sites. This study consists of a screening period of up to 4 weeks, after which subjects will receive investigational product for 48 weeks, followed by a safety follow-up period to week 52, for a total study duration of up to 56 weeks. Subjects will be randomized in a masked 1:1 ratio to receive 2 mg (0.05 mL) of either ABP 938 (Treatment Group A) or aflibercept (Treatment Group B) administered by IVT injection. At week 8, subjects will be assessed for the primary endpoint. The primary endpoint is the change in Best Corrected Visual Acuity (BCVA) as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) letter score from baseline to week 8, in order to assess the efficacy of ABP 938 compared to aflibercept. Subjects will then be re-randomized at week 16 in a masked fashion such that: * Subjects initially randomized to ABP 938 (Treatment Group A) will continue to receive ABP 938 by IVT injection every 8 weeks from week 16 until week 48 * Subjects initially randomized to aflibercept (Treatment Group B) will be re-randomized in a 1:1 ratio to either continue on aflibercept (Treatment Group B1) or transition to ABP 938 (Treatment Group B2) by IVT injection every 8 weeks from week 16 until week 48
Interventions
DRUGABP 938
Subject will receive ABP 938 2 mg (0.05 mL) IVT injection every 4 weeks for the first 3 doses, followed by once every 8 weeks
DRUGAflibercept
Subject will receive aflibercept 2 mg (0.05 mL) IVT injection every 4 weeks for the first 3 doses, followed by once every 8 weeks
Sponsors
Parexel
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
The study is double-masked; therefore, the investigators, study personnel, and the study subjects will remain masked to treatment allocation. Unmasking is only allowed in the case of an emergency, when knowledge of the investigational product is essential for the clinical management of the subject.
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects or their legally authorized representative must sign an Institutional Review Board/Independent Ethics Committee approved informed consent form before any study-specific procedures * Men or women ≥ 50 years old * Subjects must be diagnosed with neovascular (wet) AMD in the study eye * Active treatment naïve subfoveal CNV lesions secondary to neovascular (wet) AMD including juxtafoveal lesions that affect the fovea as confirmed with SD OCT, FA and/or Fundus Photography (FP) in the study eye * BCVA between 73 and 34 letters, inclusive, in the study eye using ETDRS testing * Presence of intra and/or subretinal fluid as identified by SD-OCT attributable to active CNV in the study eye * Central retinal thickness of \> 270µm in the study eye as measured by the machine, calculated average thickness in the central 1 mm subfield (CST) by SD-OCT at screening
Exclusion criteria
Subjects are excluded if they meet any of the following criteria in the study eye: * Total lesion size \> 12 disc areas (30.5 mm\^2, including blood, scars, and neovascularization) in the study eye * Active CNV area (classic plus occult components) that is \< 50% of the total lesion area in the study eye * Scar, fibrosis, or atrophy involving the center of the fovea in the study eye * Presence of retinal pigment epithelium tears or rips involving the macula in the study eye * History of any vitreous hemorrhage within 4 weeks before randomization in the study eye * Presence of other causes of CNV, including pathologic myopia (spherical equivalent of 8 diopters or more negative or axial length of 25 mm or more), ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, or multifocal choroiditis in the study eye * Prior vitrectomy or laser surgery of the macula (including photodynamic therapy or focal laser photocoagulation) in the study eye * History of retinal detachment in the study eye * Any history of macular hole of stage 2 and above in the study eye * Any macular pathology that might limit vision i.e., Vitreomacular traction or significant epiretinal membrane in the study eye * Any intraocular or periocular surgery within 3 months before randomization on the study eye, except lid surgery, which may not have taken place within 4 weeks before randomization, as long as it is unlikely to interfere with the injection * Prior trabeculectomy or other filtration surgery in the study eye * Uncontrolled glaucoma (defined as intraocular pressure ≥ 25 mmHg despite treatment with antiglaucoma medication) in the study eye * Aphakia or pseudophakia with complete absence of posterior capsule (unless it occurred as a result of a yttrium aluminum garnet \[YAG\] posterior capsulotomy) in the study eye * Previous therapeutic radiation in the region of the study eye * History of corneal transplant or corneal dystrophy in the study eye * Significant media opacities, including cataract, which might interfere with visual acuity or assessment of safety, in the study eye * Any concurrent intraocular condition other than neovascular (wet) AMD in the study eye that, in the opinion of the investigator, requires planned medical or surgical intervention during the study or increases the risk to the subject beyond what is expected from standard procedures of intraocular injection, or which otherwise may interfere with the injection procedure or with evaluation of efficacy or safety Subjects are excluded if they meet any of the following criteria in either eye: * History or clinical evidence of uveitis, diabetic retinopathy, diabetic macular edema, or any other vascular disease affecting the retina, other than neovascular (wet) AMD * Active intraocular inflammation or active or suspected ocular or periocular infection, within 2 weeks before randomization * Active scleritis or episcleritis or presence of scleromalacia Other Medical Conditions • Active extraocular infection or history of extraocular infections as follows: A. any active infection for which systemic anti-infectives were used within 4 weeks before randomization B. recurrent or chronic infections or other active infection that, in the opinion of the investigator, might cause this study to be detrimental to the subject * Acute coronary event or stroke within 3 months before randomization * Uncontrolled, clinically significant systemic disease such as diabetes mellitus, hypertension, cardiovascular disease including moderate to severe heart failure (New York Heart Association class III/IV), renal disease, or liver disease * Malignancy within 5 years EXCEPT treated and considered cured cutaneous squamous or basal cell carcinoma, in situ cervical cancer, OR in situ breast ductal carcinoma Washouts and Nonpermitted Treatments * Any prior ocular or systemic treatment, including another investigational product or surgery for neovascular (wet) AMD (including anti vascular endothelial growth factor \[VEGF\] therapy) in the study eye, except dietary supplements or vitamins * Any ocular or systemic treatment including another investigational product or surgery for neovascular (wet) AMD (including anti VEGF therapy) in the fellow eye, within 30 days before randomization, except dietary supplements or vitamins * Prior systemic anti-VEGF treatment as follows: * Investigational or approved anti-VEGF therapy systemically within 3 months before randomization * Aflibercept, ziv-aflibercept, or a biosimilar of aflibercept/ziv-aflibercept systemically at any time * Any IVT therapy, including adrenocorticotropic hormone, in the study or fellow eye, or intramuscular or intravenous corticosteroids within 4 weeks before randomization. The use of long-acting steroids, either systemically or intraocularly, in the 3 months before randomization * Currently receiving treatment with another investigational device or study drug, or less than 30 days or 5 half-lives (whichever is longer) since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded General * For women: pregnant or breast feeding, or planning to become pregnant while enrolled in the study and for 3 months after the last dose of investigational product * Sexually active subjects and their partners who are of childbearing potential (ie, neither surgically sterile nor postmenopausal) and not agreeing to use adequate contraception (eg, true abstinence, sterilization, birth control pills, Depo Provera injections, contraceptive implants, or other effective methods) while on study and for 3 months after the last dose of study drug. Male subjects must agree not to donate sperm during study and for 3 months following treatment with test article or until the scheduled end of the study (whichever is longer) * Allergy or hypersensitivity to investigational product, to any of the excipients of ABP 938 or aflibercept, or to other study-related procedures/medications (eg, anesthesia, antiseptic, fluorescein dye) * History or evidence of any other clinically significant disorder, condition, or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion * Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, Clinical Outcome Assessments) to the best of the subject and investigator's knowledge
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in BCVA at Week 8 | Baseline and Week 8 | BCVA score was assessed based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart by the study eye at 4 meters. ETDRS letters score could range from 0 to 100 letters at each assessment. A positive change from Baseline in ETDRS letter score indicated an improvement in visual acuity in the study eye. Change from Baseline calculated as observed post-baseline value - Baseline value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in BCVA | Baseline and Weeks 4, 8, 16, 24, 32, 40, 48, and 52 | BCVA score was assessed based on the number of letters read correctly on the ETDRS chart by the study eye at 4 meters. ETDRS letters score could range from 0 to 100 letters at each assessment. A positive change from Baseline in ETDRS letter score indicated an improvement in visual acuity in the study eye. Change from Baseline calculated as observed post-baseline value - Baseline value. |
| Percentage of Participants Who Gained at Least 10 Letters of Vision at Week 8 | Week 8 | Percentage of participants who gained at least 10 letters of vision was assessed based on the number of letters read correctly on the ETDRS chart by the study eye at 4 meters. ETDRS letters score could range from 0 to 100 letters at each assessment. |
| Percentage of Participants Who Gained at Least 15 Letters of Vision at Week 52 | Week 52 | Percentage of participants who gained at least 15 letters of vision was assessed based on the number of letters read correctly on the ETDRS chart by the study eye at 4 meters. ETDRS letters score could range from 0 to 100 letters at each assessment. |
| Percentage of Participants Who Maintained Vision at Week 52 | Week 52 | A participant was classified as maintaining vision if he/she lost fewer than 15 letters in ETDRS letter score, assessed in the study eye, compared to Baseline. |
| Mean Change From Baseline in Central Subfield Thickness (CST) | Baseline and Weeks 4, 8, 16, 24, 32, 40, 48, and 52 | CST was defined as the average thickness in the ETDRS central 1 mm diameter subfield (the central subfield) and was measured by spectral domain optical coherence tomography. Change from Baseline calculated as observed post-baseline value - Baseline value. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Up to Week 52 | An adverse event (AE) is any untoward medical occurrence in a clinical trial participant. TEAEs were defined as those AEs that begin or increase in severity or frequency at or after the time of first treatment to the End of Study visit. Events of interest (EOIs) pre-specified for this study included endophthalmitis, retinal detachment, increase in intraocular pressure, and thromboembolic events. Serious AEs were defined as any untoward medical occurrence that meets at least 1 of the following serious criteria: * Results in death * Life-threatening * Requires inpatient hospitalization or prolongation of existing hospitalization * Results in persistent or significant disability/incapacity * Congenital anomaly/birth defect * Other medically important serious event. |
| Number of Participants Developing Binding Antidrug Antibodies (ADAs) | Baseline up to Week 52 | Number of participants with positive post-baseline ADA result through Week 16 and post Week 16 with negative or no result at Baseline is reported. |
| Mean Change From Baseline in Choroidal Neovascularization (CNV) Area Size | Baseline and Weeks 8, 16, 24, and 52 | CNV area size was measured by fluorescein angiography. Change from Baseline calculated as observed post-baseline value - Baseline value. |
Countries
Canada, Czechia, Estonia, Germany, Hong Kong, Hungary, Israel, Italy, Japan, Latvia, Lithuania, Mexico, Poland, Serbia, Slovakia, South Korea, Spain, United States
Participant flow
Recruitment details
This study was conducted at 102 centers in Canada, Czech Republic, Estonia, Germany, Hong Kong, Hungary, Israel, Italy, Japan, South Korea, Latvia, Lithuania, Poland, Slovakia, Spain, and the United States between 22 June 2020 and 30 January 2023.
Pre-assignment details
Both eyes were assessed at the screening visit for eligibility, and only 1 eye was selected from each participant as the study eye. If both eyes met the eligibility criteria, the study eye was the one with the worse best corrected visual acuity (BCVA).
Participants by arm
| Arm | Count |
|---|---|
| ABP 938 Participants were randomized to receive 2 mg (0.05 mL) of ABP 938 by IVT injection in the study eye every 4 weeks for the first 3 doses (i.e., Baseline/Day 1, Week 4, and Week 8) and remained on ABP 938 dosing every 8 weeks from Week 16 until Week 48. | 288 |
| Aflibercept Participants were randomized to receive 2 mg (0.05 mL) of aflibercept by IVT injection in the study eye every 4 weeks for the first 3 doses (i.e., Baseline/Day 1, Week 4, and Week 8) and were re-randomized to receive aflibercept or ABP 938 dosing every 8 weeks from Week 16 until Week 48. | 288 |
| Total | 576 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Post Week 16 | Adverse Event | 7 | 5 | 1 |
| Post Week 16 | Consent Withdrawn | 4 | 3 | 6 |
| Post Week 16 | Death | 2 | 0 | 2 |
| Post Week 16 | Lost to Follow-up | 2 | 1 | 0 |
| Post Week 16 | Miscellaneous | 1 | 0 | 1 |
| Post Week 16 | Physician Decision | 3 | 1 | 1 |
| Post Week 16 | Requirement for Alternative Dosing Schedule | 2 | 1 | 0 |
| Post Week 16 | Requirement for Alternative Therapy | 1 | 0 | 0 |
| Through Week 16 | Adverse Event | 1 | 2 | 0 |
| Through Week 16 | Consent Withdrawn | 3 | 3 | 0 |
| Through Week 16 | Death | 0 | 2 | 0 |
| Through Week 16 | Lost to Follow-up | 2 | 0 | 0 |
| Through Week 16 | Miscellaneous | 1 | 1 | 0 |
| Through Week 16 | Physician Decision | 1 | 1 | 0 |
| Through Week 16 | Protocol Specified Criteria | 6 | 7 | 0 |
| Through Week 16 | Protocol Violation | 1 | 2 | 0 |
Baseline characteristics
| Characteristic | ABP 938 | Aflibercept | Total |
|---|---|---|---|
| Age, Continuous | 76.0 Years STANDARD_DEVIATION 7.93 | 76.0 Years STANDARD_DEVIATION 7.95 | 76.0 Years STANDARD_DEVIATION 7.93 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 13 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 281 Participants | 275 Participants | 556 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 36 Participants | 39 Participants | 75 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 250 Participants | 248 Participants | 498 Participants |
| Sex: Female, Male Female | 151 Participants | 171 Participants | 322 Participants |
| Sex: Female, Male Male | 137 Participants | 117 Participants | 254 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 288 | 2 / 288 | 2 / 273 | 2 / 133 | 0 / 136 |
| other Total, other adverse events | 18 / 288 | 15 / 288 | 20 / 273 | 17 / 133 | 17 / 136 |
| serious Total, serious adverse events | 6 / 288 | 9 / 288 | 22 / 273 | 14 / 133 | 11 / 136 |
Outcome results
Primary
Mean Change From Baseline in BCVA at Week 8
BCVA score was assessed based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart by the study eye at 4 meters. ETDRS letters score could range from 0 to 100 letters at each assessment. A positive change from Baseline in ETDRS letter score indicated an improvement in visual acuity in the study eye. Change from Baseline calculated as observed post-baseline value - Baseline value.
Time frame: Baseline and Week 8
Population: Full Analysis Set: Consisted of all randomized participants, with treatment as the randomized treatment regardless of actual treatment received. Participants were included in the treatment group in which they were initially randomized. Analysis included participants with available data at Baseline and Week 8.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABP 938 | Mean Change From Baseline in BCVA at Week 8 | 6.4 Letters | Standard Deviation 8.18 |
| Aflibercept | Mean Change From Baseline in BCVA at Week 8 | 6.5 Letters | Standard Deviation 8.97 |
Comparison: Difference in mean change from Baseline at Week 8.90% CI: [-1.1, 1.3]
Secondary
Mean Change From Baseline in BCVA
BCVA score was assessed based on the number of letters read correctly on the ETDRS chart by the study eye at 4 meters. ETDRS letters score could range from 0 to 100 letters at each assessment. A positive change from Baseline in ETDRS letter score indicated an improvement in visual acuity in the study eye. Change from Baseline calculated as observed post-baseline value - Baseline value.
Time frame: Baseline and Weeks 4, 8, 16, 24, 32, 40, 48, and 52
Population: Full Analysis Set (Re-randomized): Consisted of all randomized participants, with treatment as the re-randomized treatment regardless of actual treatment received. Participants were included in the treatment group in which they were re-randomized. Analysis included participants with available data at Baseline and at each timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ABP 938 | Mean Change From Baseline in BCVA | Week 4 | 5.0 Letters | Standard Deviation 6.57 |
| ABP 938 | Mean Change From Baseline in BCVA | Week 8 | 6.5 Letters | Standard Deviation 8.1 |
| ABP 938 | Mean Change From Baseline in BCVA | Week 16 | 6.8 Letters | Standard Deviation 8.69 |
| ABP 938 | Mean Change From Baseline in BCVA | Week 24 | 7.2 Letters | Standard Deviation 9.63 |
| ABP 938 | Mean Change From Baseline in BCVA | Week 32 | 7.1 Letters | Standard Deviation 11 |
| ABP 938 | Mean Change From Baseline in BCVA | Week 40 | 7.3 Letters | Standard Deviation 11 |
| ABP 938 | Mean Change From Baseline in BCVA | Week 48 | 7.2 Letters | Standard Deviation 11.51 |
| ABP 938 | Mean Change From Baseline in BCVA | Week 52 | 7.6 Letters | Standard Deviation 11.6 |
| Aflibercept | Mean Change From Baseline in BCVA | Week 16 | 7.5 Letters | Standard Deviation 9.31 |
| Aflibercept | Mean Change From Baseline in BCVA | Week 48 | 8.7 Letters | Standard Deviation 10.84 |
| Aflibercept | Mean Change From Baseline in BCVA | Week 24 | 7.1 Letters | Standard Deviation 9.3 |
| Aflibercept | Mean Change From Baseline in BCVA | Week 32 | 8.7 Letters | Standard Deviation 9.21 |
| Aflibercept | Mean Change From Baseline in BCVA | Week 40 | 8.1 Letters | Standard Deviation 11 |
| Aflibercept | Mean Change From Baseline in BCVA | Week 4 | 5.4 Letters | Standard Deviation 8.35 |
| Aflibercept | Mean Change From Baseline in BCVA | Week 8 | 7.6 Letters | Standard Deviation 9.3 |
| Aflibercept | Mean Change From Baseline in BCVA | Week 52 | 9.4 Letters | Standard Deviation 10.18 |
| Aflibercept / ABP 938 | Mean Change From Baseline in BCVA | Week 16 | 7.1 Letters | Standard Deviation 9.32 |
| Aflibercept / ABP 938 | Mean Change From Baseline in BCVA | Week 8 | 5.6 Letters | Standard Deviation 8.86 |
| Aflibercept / ABP 938 | Mean Change From Baseline in BCVA | Week 4 | 3.8 Letters | Standard Deviation 8.19 |
| Aflibercept / ABP 938 | Mean Change From Baseline in BCVA | Week 24 | 7.0 Letters | Standard Deviation 10.12 |
| Aflibercept / ABP 938 | Mean Change From Baseline in BCVA | Week 48 | 8.1 Letters | Standard Deviation 10.74 |
| Aflibercept / ABP 938 | Mean Change From Baseline in BCVA | Week 40 | 7.9 Letters | Standard Deviation 10.08 |
| Aflibercept / ABP 938 | Mean Change From Baseline in BCVA | Week 32 | 6.6 Letters | Standard Deviation 11.11 |
| Aflibercept / ABP 938 | Mean Change From Baseline in BCVA | Week 52 | 8.0 Letters | Standard Deviation 11.14 |
Comparison: Difference in mean change from Baseline at Week 4.90% CI: [-1.3, 1.2]
Comparison: Difference in mean change from Baseline at Week 8.90% CI: [-2.3, 0.7]
Comparison: Difference in mean change from Baseline at Week 16.90% CI: [-1.9, 1.2]
Comparison: Difference in mean change from Baseline at Week 24.90% CI: [-1.3, 2.1]
Comparison: Difference in mean change from Baseline at Week 32.90% CI: [-3.1, 0.5]
Comparison: Difference in mean change from Baseline at Week 40.90% CI: [-2.3, 1.4]
Comparison: Difference in mean change from Baseline at Week 48.90% CI: [-3.2, 0.8]
Comparison: Difference in mean change from Baseline at Week 52.2% CI: [-3.4, 0.5]
Comparison: Difference in mean change from Baseline at Week 4.90% CI: [-3, 0]
Comparison: Difference in mean change from Baseline at Week 8.90% CI: [-3.6, -0.2]
Comparison: Difference in mean change from Baseline at Week 16.90% CI: [-2.1, 1.5]
Comparison: Difference in mean change from Baseline at Week 24.90% CI: [-1.9, 2]
Comparison: Difference in mean change from Baseline at Week 32.90% CI: [-4, 0.2]
Comparison: Difference in mean change from Baseline at Week 40.90% CI: [-2.2, 2.2]
Comparison: Difference in mean change from Baseline at Week 48.90% CI: [-2.9, 1.7]
Comparison: Difference in mean change from Baseline at Week 52.90% CI: [-3.5, 1.1]
Secondary
Mean Change From Baseline in Central Subfield Thickness (CST)
CST was defined as the average thickness in the ETDRS central 1 mm diameter subfield (the central subfield) and was measured by spectral domain optical coherence tomography. Change from Baseline calculated as observed post-baseline value - Baseline value.
Time frame: Baseline and Weeks 4, 8, 16, 24, 32, 40, 48, and 52
Population: Full Analysis Set (Re-randomized): Consisted of all randomized participants, with treatment as the re-randomized treatment regardless of actual treatment received. Participants were included in the treatment group in which they were re-randomized. Analysis included participants with available data at Baseline and at each timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ABP 938 | Mean Change From Baseline in Central Subfield Thickness (CST) | Week 52 | -157.1 μm | Standard Deviation 114.25 |
| ABP 938 | Mean Change From Baseline in Central Subfield Thickness (CST) | Week 4 | -136.5 μm | Standard Deviation 108.91 |
| ABP 938 | Mean Change From Baseline in Central Subfield Thickness (CST) | Week 24 | -130.8 μm | Standard Deviation 125.63 |
| ABP 938 | Mean Change From Baseline in Central Subfield Thickness (CST) | Week 16 | -125.2 μm | Standard Deviation 124.81 |
| ABP 938 | Mean Change From Baseline in Central Subfield Thickness (CST) | Week 8 | -145.9 μm | Standard Deviation 106.24 |
| ABP 938 | Mean Change From Baseline in Central Subfield Thickness (CST) | Week 32 | -133.2 μm | Standard Deviation 122.93 |
| ABP 938 | Mean Change From Baseline in Central Subfield Thickness (CST) | Week 48 | -132.3 μm | Standard Deviation 124.15 |
| ABP 938 | Mean Change From Baseline in Central Subfield Thickness (CST) | Week 40 | -132.3 μm | Standard Deviation 113.25 |
| Aflibercept | Mean Change From Baseline in Central Subfield Thickness (CST) | Week 8 | -146.3 μm | Standard Deviation 110.39 |
| Aflibercept | Mean Change From Baseline in Central Subfield Thickness (CST) | Week 40 | -135.6 μm | Standard Deviation 119.07 |
| Aflibercept | Mean Change From Baseline in Central Subfield Thickness (CST) | Week 4 | -143.1 μm | Standard Deviation 107.32 |
| Aflibercept | Mean Change From Baseline in Central Subfield Thickness (CST) | Week 48 | -141.1 μm | Standard Deviation 112.29 |
| Aflibercept | Mean Change From Baseline in Central Subfield Thickness (CST) | Week 52 | -159.1 μm | Standard Deviation 108.82 |
| Aflibercept | Mean Change From Baseline in Central Subfield Thickness (CST) | Week 16 | -127.3 μm | Standard Deviation 103.35 |
| Aflibercept | Mean Change From Baseline in Central Subfield Thickness (CST) | Week 24 | -131.7 μm | Standard Deviation 102.98 |
| Aflibercept | Mean Change From Baseline in Central Subfield Thickness (CST) | Week 32 | -134.1 μm | Standard Deviation 116.02 |
| Aflibercept / ABP 938 | Mean Change From Baseline in Central Subfield Thickness (CST) | Week 52 | -177.4 μm | Standard Deviation 122.22 |
| Aflibercept / ABP 938 | Mean Change From Baseline in Central Subfield Thickness (CST) | Week 4 | -149.7 μm | Standard Deviation 107.01 |
| Aflibercept / ABP 938 | Mean Change From Baseline in Central Subfield Thickness (CST) | Week 8 | -167.4 μm | Standard Deviation 118.52 |
| Aflibercept / ABP 938 | Mean Change From Baseline in Central Subfield Thickness (CST) | Week 16 | -143.2 μm | Standard Deviation 121.93 |
| Aflibercept / ABP 938 | Mean Change From Baseline in Central Subfield Thickness (CST) | Week 24 | -151.2 μm | Standard Deviation 118.21 |
| Aflibercept / ABP 938 | Mean Change From Baseline in Central Subfield Thickness (CST) | Week 32 | -154.8 μm | Standard Deviation 114.22 |
| Aflibercept / ABP 938 | Mean Change From Baseline in Central Subfield Thickness (CST) | Week 40 | -155.7 μm | Standard Deviation 119.95 |
| Aflibercept / ABP 938 | Mean Change From Baseline in Central Subfield Thickness (CST) | Week 48 | -157.8 μm | Standard Deviation 121.23 |
Comparison: Difference in mean change from Baseline at Week 4.90% CI: [-5.6, 17.9]
Comparison: Difference in mean change from Baseline at Week 8.90% CI: [-11, 13.5]
Comparison: Difference in mean change from Baseline at Week 16.90% CI: [-12.9, 16.6]
Comparison: Difference in mean change from Baseline at Week 24.90% CI: [-14.1, 14.4]
Comparison: Difference in mean change from Baseline at Week 32.90% CI: [-15.3, 12.9]
Comparison: Difference in mean change from Baseline at Week 40.90% CI: [-13.7, 14.1]
Comparison: Difference in mean change from Baseline at Week 48.90% CI: [-7.4, 21.4]
Comparison: Difference in mean change from Baseline at Week 52.2% CI: [-9.3, 12.5]
Comparison: Difference in mean change from Baseline at Week 4.90% CI: [-7.4, 20]
Comparison: Difference in mean change from Baseline at Week 8.90% CI: [-19.3, 9.1]
Comparison: Difference in mean change from Baseline at Week 16.90% CI: [-20.9, 13.3]
Comparison: Difference in mean change from Baseline at Week 24.90% CI: [-22.6, 10.6]
Comparison: Difference in mean change from Baseline at Week 32.90% CI: [-23.3, 9.3]
Comparison: Difference in mean change from Baseline at Week 40.90% CI: [-22.8, 9.8]
Comparison: Difference in mean change from Baseline at Week 48.90% CI: [-17.3, 16.2]
Comparison: Difference in mean change from Baseline at Week 52.90% CI: [-10.5, 15]
Secondary
Mean Change From Baseline in Choroidal Neovascularization (CNV) Area Size
CNV area size was measured by fluorescein angiography. Change from Baseline calculated as observed post-baseline value - Baseline value.
Time frame: Baseline and Weeks 8, 16, 24, and 52
Population: Full Analysis Set (Re-randomized): Consisted of all randomized participants, with treatment as the re-randomized treatment regardless of actual treatment received. Participants were included in the treatment group in which they were re-randomized. Analysis included participants with available data at Baseline and at each timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ABP 938 | Mean Change From Baseline in Choroidal Neovascularization (CNV) Area Size | Week 8 | -4.962 mm^2 | Standard Deviation 5.1604 |
| ABP 938 | Mean Change From Baseline in Choroidal Neovascularization (CNV) Area Size | Week 16 | -4.089 mm^2 | Standard Deviation 5.3668 |
| ABP 938 | Mean Change From Baseline in Choroidal Neovascularization (CNV) Area Size | Week 24 | -4.323 mm^2 | Standard Deviation 5.5972 |
| ABP 938 | Mean Change From Baseline in Choroidal Neovascularization (CNV) Area Size | Week 52 | -6.276 mm^2 | Standard Deviation 6.269 |
| Aflibercept | Mean Change From Baseline in Choroidal Neovascularization (CNV) Area Size | Week 52 | -7.280 mm^2 | Standard Deviation 5.8262 |
| Aflibercept | Mean Change From Baseline in Choroidal Neovascularization (CNV) Area Size | Week 8 | -5.479 mm^2 | Standard Deviation 5.1023 |
| Aflibercept | Mean Change From Baseline in Choroidal Neovascularization (CNV) Area Size | Week 24 | -5.308 mm^2 | Standard Deviation 5.6238 |
| Aflibercept | Mean Change From Baseline in Choroidal Neovascularization (CNV) Area Size | Week 16 | -5.174 mm^2 | Standard Deviation 5.228 |
| Aflibercept / ABP 938 | Mean Change From Baseline in Choroidal Neovascularization (CNV) Area Size | Week 52 | -6.434 mm^2 | Standard Deviation 5.2445 |
| Aflibercept / ABP 938 | Mean Change From Baseline in Choroidal Neovascularization (CNV) Area Size | Week 16 | -4.751 mm^2 | Standard Deviation 4.8814 |
| Aflibercept / ABP 938 | Mean Change From Baseline in Choroidal Neovascularization (CNV) Area Size | Week 24 | -5.121 mm^2 | Standard Deviation 5.2776 |
| Aflibercept / ABP 938 | Mean Change From Baseline in Choroidal Neovascularization (CNV) Area Size | Week 8 | -5.169 mm^2 | Standard Deviation 4.6943 |
Comparison: Difference in mean change from Baseline at Week 8.90% CI: [-0.734, 0.638]
Comparison: Difference in mean change from Baseline at Week 16.90% CI: [-0.367, 1.229]
Comparison: Difference in mean change from Baseline at Week 24.90% CI: [-0.625, 1.019]
Comparison: Difference in mean change from Baseline at Week 52.2% CI: [-0.561, 0.872]
Comparison: Difference in mean change from Baseline at Week 8.90% CI: [-0.682, 0.891]
Comparison: Difference in mean change from Baseline at Week 16.90% CI: [-0.667, 1.158]
Comparison: Difference in mean change from Baseline at Week 24.90% CI: [-1.065, 0.834]
Comparison: Difference in mean change from Baseline at Week 52.90% CI: [-0.186, 1.479]
Secondary
Number of Participants Developing Binding Antidrug Antibodies (ADAs)
Number of participants with positive post-baseline ADA result through Week 16 and post Week 16 with negative or no result at Baseline is reported.
Time frame: Baseline up to Week 52
Population: Safety Analysis Set (Re-randomized and Treated): Consisted of all participants who received at least 1 dose of investigational product, with treatment assignment based on actual treatment received. Analysis included participants with available data at Baseline and at each timepoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ABP 938 | Number of Participants Developing Binding Antidrug Antibodies (ADAs) | 1 Participants |
| Aflibercept | Number of Participants Developing Binding Antidrug Antibodies (ADAs) | 4 Participants |
| Aflibercept / ABP 938 | Number of Participants Developing Binding Antidrug Antibodies (ADAs) | 4 Participants |
| Post Week 16: Aflibercept / ABP 938 | Number of Participants Developing Binding Antidrug Antibodies (ADAs) | 3 Participants |
| Post Week 16: Aflibercept / Aflibercept | Number of Participants Developing Binding Antidrug Antibodies (ADAs) | 0 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) is any untoward medical occurrence in a clinical trial participant. TEAEs were defined as those AEs that begin or increase in severity or frequency at or after the time of first treatment to the End of Study visit. Events of interest (EOIs) pre-specified for this study included endophthalmitis, retinal detachment, increase in intraocular pressure, and thromboembolic events. Serious AEs were defined as any untoward medical occurrence that meets at least 1 of the following serious criteria: * Results in death * Life-threatening * Requires inpatient hospitalization or prolongation of existing hospitalization * Results in persistent or significant disability/incapacity * Congenital anomaly/birth defect * Other medically important serious event.
Time frame: Up to Week 52
Population: Safety Analysis Set: Consisted of all participants who received at least 1 dose of investigational product, with treatment assignment based on actual treatment received. TEAEs were collected for all participants who were re-randomized and received at least one dose of study drug post Week 16.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ABP 938 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any EOIs | 6 Participants |
| ABP 938 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any TEAEs | 113 Participants |
| ABP 938 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any Serious TEAEs | 6 Participants |
| Aflibercept | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any TEAEs | 107 Participants |
| Aflibercept | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any Serious TEAEs | 9 Participants |
| Aflibercept | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any EOIs | 3 Participants |
| Aflibercept / ABP 938 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any TEAEs | 144 Participants |
| Aflibercept / ABP 938 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any EOIs | 9 Participants |
| Aflibercept / ABP 938 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any Serious TEAEs | 22 Participants |
| Post Week 16: Aflibercept / ABP 938 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any Serious TEAEs | 14 Participants |
| Post Week 16: Aflibercept / ABP 938 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any TEAEs | 76 Participants |
| Post Week 16: Aflibercept / ABP 938 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any EOIs | 8 Participants |
| Post Week 16: Aflibercept / Aflibercept | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any EOIs | 2 Participants |
| Post Week 16: Aflibercept / Aflibercept | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any TEAEs | 72 Participants |
| Post Week 16: Aflibercept / Aflibercept | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any Serious TEAEs | 11 Participants |
Secondary
Percentage of Participants Who Gained at Least 10 Letters of Vision at Week 8
Percentage of participants who gained at least 10 letters of vision was assessed based on the number of letters read correctly on the ETDRS chart by the study eye at 4 meters. ETDRS letters score could range from 0 to 100 letters at each assessment.
Time frame: Week 8
Population: Full Analysis Set: Consisted of all randomized participants, with treatment as the randomized treatment regardless of actual treatment received. Participants were included in the treatment group in which they were initially randomized. Analysis included participants with available data at Baseline and Week 8.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABP 938 | Percentage of Participants Who Gained at Least 10 Letters of Vision at Week 8 | 29.4 Percentage of participants |
| Aflibercept | Percentage of Participants Who Gained at Least 10 Letters of Vision at Week 8 | 32.7 Percentage of participants |
Comparison: Risk difference in percentage of participants who gained at least 10 letters of vision at Week 8.90% CI: [-9.8, 3.1]
Secondary
Percentage of Participants Who Gained at Least 15 Letters of Vision at Week 52
Percentage of participants who gained at least 15 letters of vision was assessed based on the number of letters read correctly on the ETDRS chart by the study eye at 4 meters. ETDRS letters score could range from 0 to 100 letters at each assessment.
Time frame: Week 52
Population: Full Analysis Set (Re-randomized): Consisted of all re-randomized participants, with treatment as the randomized treatment regardless of actual treatment received. Participants were included in the treatment group in which they were re-randomized. Analysis included participants with available data at Baseline and Week 52.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABP 938 | Percentage of Participants Who Gained at Least 15 Letters of Vision at Week 52 | 24.3 Percentage of participants |
| Aflibercept | Percentage of Participants Who Gained at Least 15 Letters of Vision at Week 52 | 29.6 Percentage of participants |
| Aflibercept / ABP 938 | Percentage of Participants Who Gained at Least 15 Letters of Vision at Week 52 | 24.4 Percentage of participants |
Comparison: Risk difference in percentage of participants who gained at least 15 letters of vision at Week 52.90% CI: [-13.6, 2.5]
Comparison: Risk difference in percentage of participants who gained at least 15 letters of vision at Week 52.90% CI: [-14.4, 4.2]
Secondary
Percentage of Participants Who Maintained Vision at Week 52
A participant was classified as maintaining vision if he/she lost fewer than 15 letters in ETDRS letter score, assessed in the study eye, compared to Baseline.
Time frame: Week 52
Population: Full Analysis Set (Re-randomized): Consisted of all re-randomized participants, with treatment as the randomized treatment regardless of actual treatment received. Participants were included in the treatment group in which they were re-randomized. Analysis included participants with available data at Baseline and Week 52.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABP 938 | Percentage of Participants Who Maintained Vision at Week 52 | 95.6 Percentage of Participants |
| Aflibercept | Percentage of Participants Who Maintained Vision at Week 52 | 97.6 Percentage of Participants |
| Aflibercept / ABP 938 | Percentage of Participants Who Maintained Vision at Week 52 | 95.9 Percentage of Participants |
Comparison: Risk difference in percentage of participants who maintained vision at Week 52.90% CI: [-5.2, 2.2]
Comparison: Risk difference in percentage of participants who maintained vision at Week 52.90% CI: [-6.2, 2.8]