Neovascular Age-Related Macular Degeneration MedDRA version: 27.0 Level: PT Classification code 10071129 Term: Neovascular age-related macular degeneration System Organ Class: 10015919 - Eye disorders
Conditions
Sponsors
Bayer AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. At least 50 years of age at the time of signing the informed consent. 2. Active subfoveal CNV secondary to nAMD, including juxtafoveal lesions that affect the fovea as assessed in the study eye. 3. Total area of CNV (including both classic and occult components) must comprise greater than 50% of the total lesion area in the study eye. 4. BCVA ETDRS letter score of 78 to 24 (corresponding to a Snellen equivalent of approximately 20/32 to 20/320) in the study eye. 5. Decrease in BCVA determined to be primarily the result of nAMD in the study eye. 6. Presence of IRF and/or SRF affecting the central subfield of the study eye on OCT. The central subfield is defined as a circle with diameter 1 mm, centered on the fovea. 7. Male or female. All randomized participants that complete Week 96 are eligible for the extension period, as long as the following criteria apply: 1. The participant provides signed informed consent to participate in the extension period, and no treatment for nAMD has been given in the study eye outside of the randomized study treatment. 2. At least one BCVA value and one central subfield retinal thickness (CST) value from measurements at one of the following visits: Visit 24 (Week 84), Visit 25 (Week 88) or Visit 26 (Week 92). 3. Participant is enrolled at a site that participates in the extension period. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 288 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 672
Exclusion criteria
Exclusion criteria: 1. Causes of CNV other than nAMD in the study eye. 2. Prior or concomitant conditions in the study eye: a. Subretinal hemorrhage that is at least 50% of the total lesion area, or if the blood under the fovea is 1 or more disc areas in size in the study eye. b. Scar or fibrosis making up more than 50% of the total lesion in the study eye. c. Scar, fibrosis, or atrophy involving the central subfield in the study eye. d. Presence of retinal pigment epithelial tears or rips involving the central subfield in the study eye. e. Total lesion size >12 disc areas (30.5 mm2, including blood, scars, and neovascularization) as assessed by FA in the study eye. f. Uncontrolled glaucoma (defined as IOP >25 mmHg despite treatment with anti-glaucoma medication) in the study eye. g. History of idiopathic or autoimmune uveitis in the study eye. h. Vitreomacular traction or epiretinal membrane in the study eye evident on biomicroscopy or OCT that is thought to affect central vision. i. Any history of macular hole of stage 2 and above in the study eye. j. Structural damage to the center of the macula in the study eye that is likely to preclude improvement in BCVA following the resolution of retinal fluid including but not limited to, atrophy of the retinal pigment epithelium, subretinal fibrosis or scar or significant macular ischemia. k. History of, or likely future need of, filtration or tube shunt surgery on the study eye. l. Aphakia, or pseudophakia with absence of posterior capsule (unless it occurred as a result of a yttrium-aluminium-garnet [YAG] posterior capsulotomy performed more than 4 weeks (28 days) before screening), in the study eye. m. Myopia of a spherical equivalent of at least 8 diopters in the study eye prior to any refractive or cataract surgery. n. Significant media opacities, including cataract, that interfere with BCVA assessment, fundus photography or OCT imaging in the study eye. o. History of corneal transplant or corneal dystrophy in the study eye. p. History of irregular astigmatism or amblyopia with chronic limitation of BCVA in the study eye. 3. Prior or concomitant conditions of the study participant: a. History or clinical evidence of diabetic retinopathy, diabetic macular edema, or any retinal vascular disease other than nAMD in either eye. b. Evidence of extraocular or periocular infection or inflammation (including infectious blepharitis, keratitis, scleritis, or conjunctivitis) in either eye at the time of screening/randomization. c. Any intraocular inflammation/infection in either eye within 12 weeks (84 days) of the screening visit. d. Only 1 functional eye, even if that eye was otherwise eligible for the study (e.g., BCVA of counting fingers or less in the eye with worse vision). e. Ocular conditions with poorer prognosis in the fellow eye. 4. Uncontrolled blood pressure (defined as systolic >160 mmHg or diastolic >95 mmHg). 5. History of cerebrovascular accident or myocardial infarction within 24 weeks (168 days) before the screening visit. 6. Renal failure requiring dialysis, or renal transplant at screening or potentially during the study. 7. Any prior or concomitant ocular (in the study eye) or systemic treatment (with an investigational or approved, anti-VEGF or other agent) or surgery for nAMD, except dietary supplements or vitamins. 8. Prior treatment of the study eye with any of the following drugs (any route of ophthalmic administration) or procedures before baseline visit (Day 1): a. Anti-angioge
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine if treatment with aflibercept 8 mg (HD) at intervals of 12 or 16 weeks provides non-inferior BCVA change compared to aflibercept 2 mg every 8 weeks in participants with nAMD;Secondary Objective: - To determine the effect of HD versus 2 mg aflibercept on other visual and anatomic measures of response - To assess the efficacy of HD compared to 2 mg aflibercept on vision related quality of life - To evaluate the safety, pharmacokinetics (PK) and immunogenicity of aflibercept;Primary end point(s): Change from baseline in BCVA measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score at Week 48;Timepoint(s) of evaluation of this end point: at 48 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Change from baseline in BCVA measured by the ETDRS letter score at Week 60 2. Proportion of participants with no intraretinal fluid (IRF) and no subretinal fluid (SRF) in central subfield at Week 16 3. Proportion of participants gaining at least 15 letters in BCVA from baseline at Week 48 4. Proportion of participants achieving an ETDRS letter score of at least 69 (approximate 20/40 Snellen equivalent) at Week 48 5. Change in choroidal neovascularization (CNV) size from baseline to Week 48 6. Change in total lesion area from baseline to Week 48 7. Proportion of participants with no IRF and no SRF in the center subfield at Week 48 8. Change from baseline in central subfield retinal thickness (CST) at Week 48 9. Change from baseline in National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) total score at Week 48 10. Treatment-emergent adverse events (AEs) and serious AEs (SAEs) through Week 48, 60, 96 and, for participants who continue in the study extension, through Week 156 11. Systemic exposure to aflibercept as assessed by plasma concentrations of free, bound, adjusted bound and total aflibercept from baseline through Week 48 12. Assessment of immunogenicity to aflibercept by measuring the incidence of treatment-emergent anti-drug antibodies (ADA) response through end of masked study (week 96);Timepoint(s) of evaluation of this end point: 1. at baseline and week 60 2. at week 16 3. at baseline and week 48 4. at week 48 5. at baseline and week 48 6. at baseline and week 48 7. at week 48 8. at baseline and week 48 9. at baseline and week 48 10. up to 96 / 156 weeks 11. at week 48 12. at week 96 | — |
Countries
Argentina, Australia, Austria, Belarus, Belgium, Brazil, Bulgaria, Canada, China, Colombia, Czechia, Czech Republic, Denmark, Estonia, France, Georgia, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Latvia, Lithuania, Mexico, Netherlands, Portugal, Russian Federation, Serbia, Singapore, Slovakia, Spain, Switzerland, Taiwan, Türkiye, Ukraine, United Kingdom, United States
Contacts
Public ContactBayer Clinical Trials Contact
Bayer AG
Outcome results
None listed