Study of the efficacy and safety of high-dose Aflibercept in patients with neovascular (wet) age-related macular degeneration (nAMD)
Summary description of the study
This study aims to investigate whether the investigational drug Aflibercept 8 mg can help extend the time between injections and/or improve vision. This will be compared to Aflibercept 2 mg, the currently approved and marketed therapy for nAMD. In nAMD, abnormal growth of new blood vessels occurs in the macula, which can cause swelling and bleeding in the eye and ultimately lead to deterioration or loss of vision. It is not known whether Aflibercept 8 mg has any benefit compared to the treatment that your doctor would normally prescribe. By participating in this clinical study, you can help find an answer to this question.
(BASEC)
Intervention under investigation
You will undergo a preliminary examination lasting up to 3 weeks. This will involve blood being drawn, you will be asked to provide a urine sample, and a detailed examination of the eyes will be conducted. Additionally, you will be asked questions about your medical history in the past and present.
Upon completion of the preliminary examination, you will be assigned to one of 3 treatment groups: Aflibercept 2 mg every 8 weeks compared to Aflibercept 8 mg every 12 weeks or Aflibercept 8 mg every 16 weeks.
At the start, you will receive 3 injections at 4-week intervals. You will be asked to come to the hospital 27 times over a period of 99 weeks. Each visit will last about 2 to 4 hours. At certain visit appointments during the study, blood will be drawn. The total duration of the study is about 2 years.
(BASEC)
Disease under investigation
Eye disease: Neovascular (wet) age-related macular degeneration (nAMD)
(BASEC)
You are 50 years old or older You have been diagnosed with nAMD You are not currently receiving any treatment for nAMD (BASEC)
Exclusion criteria
Other causes of symptoms than nAMD Certain pre-existing and concurrent eye conditions Pre-treatment of the eye with certain medications (BASEC)
Trial sites
Basel, Bern, Lausanne, Zurich
(BASEC)
Sponsor
not available
Contact
Contact Person Switzerland
Prof. Dr. Christian Pruente
+41 61 265 86 81
christian.pruente@clutterusb.ch(BASEC)
Scientific Information
not available
Name of the authorising ethics committee (for multicentre studies, only the lead committee)
Ethics Committee northwest/central Switzerland EKNZ
(BASEC)
Date of authorisation
16.12.2020
(BASEC)
ICTRP Trial ID
NCT04423718 (ICTRP)
Official title (approved by ethics committee)
not available
Academic title
Randomized, Double-Masked, Active-Controlled, Phase 3 Study of the Efficacy and Safety of High Dose Aflibercept in Patients With Neovascular Age-Related Macular Degeneration (ICTRP)
Public title
Study of the Effects of High Dose Aflibercept Injected Into the Eye of Patients With an Age-related Disorder That Causes Loss of Vision Due to Growth of Abnormal Blood Vessels at the Back of the Eye (ICTRP)
Disease under investigation
Neovascular Age-Related Macular Degeneration (ICTRP)
Intervention under investigation
Drug: Aflibercept High Dose VEGF Trap-Eye (BAY86-5321);Drug: Aflibercept VEGF Trap-Eye (Eylea, BAY86-5321) (ICTRP)
Type of trial
Interventional (ICTRP)
Trial design
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor). (ICTRP)
Inclusion/Exclusion criteria
Gender: All
Maximum age: N/A
Minimum age: 50 Years
Inclusion Criteria:
- Active subfoveal CNV secondary to nAMD, including juxtafoveal lesions that affect
the fovea as assessed in the study eye.
- Total area of CNV (including both classic and occult components) must comprise
greater than 50% of the total lesion area in the study eye.
- BCVA ETDRS letter score of 78 to 24 (corresponding to a Snellen equivalent of
approximately 20/32 to 20/320) in the study eye.
- Decrease in BCVA determined to be primarily the result of nAMD in the study eye.
- Presence of IRF and/or SRF affecting the central subfield of the study eye on OCT.
- Contraceptive use by men or women should be consistent with local regulations
regarding the methods of highly effective contraception for those participating in
clinical studies.
- Other protocol-specified inclusion criteria.
Additional inclusion criteria for Year 3:
- 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).
- Participant is enrolled at a site that participates in the extension period.
Exclusion Criteria:
- Causes of CNV other than nAMD in the study eye.
- Scar, fibrosis, or atrophy involving the central subfield in the study eye.
- Presence of retinal pigment epithelial tears or rips involving the central subfield
in the study eye.
- Uncontrolled glaucoma (defined as IOP >25 mmHg despite treatment with anti-glaucoma
medication) in the study eye.
- History of idiopathic or autoimmune uveitis in the study eye.
- Myopia of a spherical equivalent of at least 8 diopters in the study eye prior to
any refractive or cataract surgery.
- History or clinical evidence of diabetic retinopathy, diabetic macular edema, or any
retinal vascular disease other than nAMD in either eye.
- Evidence of extraocular or periocular infection or inflammation (including
infectious blepharitis, keratitis, scleritis, or conjunctivitis) in either eye at
the time of screening/randomization.
- Uncontrolled blood pressure (defined as systolic >160 mmHg or diastolic >95 mmHg).
- 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.
- Other protocol-specified exclusion criteria (ICTRP)
not available
Primary and secondary end points
Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 48 (ICTRP)
Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 60;Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in Central Subfield at Week 16;Percentage of Participants Gaining at Least 15 Letters in BCVA From Baseline at Week 48;Percentage of Participants Achieving an ETDRS Letter Score of at Least 69 (Approximate 20/40 Snellen Equivalent) at Week 48;Change in Choroidal Neovascularization (CNV) Size From Baseline to Week 48;Change in Total Lesion Area From Baseline to Week 48;Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in the Center Subfield at Week 48;Change From Baseline in Central Subfield Retinal Thickness (CST) at Week 48;Change From Baseline in National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) Total Score at Week 48;Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs);Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Week 48;Assessment of Immunogenicity to Aflibercept by Measuring the Incidence of Treatment-emergent Anti-drug Antibodies (ADA) Response Through End of Masked Study (ICTRP)
Registration date
not available
Incorporation of the first participant
not available
Secondary sponsors
Regeneron Pharmaceuticals (ICTRP)
Additional contacts
not available
Secondary trial IDs
2019-003851-12, 20968 (ICTRP)
Results-Individual Participant Data (IPD)
not available
Further information on the trial
https://clinicaltrials.gov/ct2/show/NCT04423718 (ICTRP)
Results of the trial
Results summary
not available
Link to the results in the primary register
not available