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About
This is a prospective, randomized study that compares 8-week and 12-week follow-up intervals after the 4 monthly injections in the loading phase. Patients with active CNV confirmed on optical coherence tomography (OCT) and OCT angiography (OCTA) will be randomized into two groups and followed for 44 to 56 weeks.
Patients in the first group will receive 4 injections of faricimab every 4 weeks, with the next visit and injection after 8 weeks, followed by a treat-and-extend regimen with a minimal interval of 8 weeks and a maximal interval of 16 weeks.
Patients in the second group will also receive 4 loading doses with the next visit after an extended 12-week interval. Following treatment, patients in this group will be on the same treat-and-extend regimen as patients in the first group. The study will compare best corrected visual acuity (BCVA), central retinal thickness (CRT) on OCT, and the number of injections between both groups.
Full description
Wet age-related macular degeneration (wet AMD) is a progressive eye disease that affects the macula, the part of the retina responsible for sharp central vision. The treatment of wet AMD choroidal neovascularization (CNV) with intravitreal antiVEGF drugs is highly effective. In our study, we aim to compare the efficacy of standard (8 weeks) versus extended follow-up dosing interval (12 weeks) following 4 monthly loading injections of the new combined-mechanism medication, faricimab (6 mg intravitreal dose), which targets both VEGF-A and Ang-2 receptors, in the treatment of wet AMD. We will include all types of CNVs in our study, including Type 1 (occult), Type 2 (classic), Type 3 CNV (Retinal Angiomatous Proliferation = RAP) and mixed CNV. This is a prospective, randomised, comparative study comparing the best corrected visual acuity (BCVA) and central retinal thickness (CRT) on optical coherence tomography (OCT) in the 20th, 24th week of the study between both groups. The total number of injections between both groups will be also compared at the final visit, which will take place between the 44th and 56th week of the study based on the dosing interval.
Patients in the first group will receive 4 injections of faricimab every 4 weeks, with the next visit and injection after 8 weeks (Week 20 Visit), followed by a treat-and-extend regimen with a minimal interval of 8 weeks and a maximal interval of 16 weeks.
Patients in the second group will also receive 4 loading doses with the next visit after an extended 12-week interval (Week 24 Visit). Following treatment, patients in this group will be on the same treat-and-extend regimen as patients in the first group. The study will compare best corrected visual acuity (BCVA), central retinal thickness (CRT) on OCT, and the number of injections between both groups.
Visit plan:
Screening visit - 14 to 0 day prior to baseline. Informed consent will be signed prior to any other study procedures. Ocular and medical history will be written down. BCVA of both eyes will be tested on ETDRS charts. Non-contact intraocular pressure (IOP) will be measured. Slit lamp anterior segment examination and fundus biomicroscopy of both eyes will be performed in artificial mydriasis. The OCT scan of both eyes will be performed, and OCTA will be performed in the treatment naïve eyes. Based on the examination results, patients' eligibility for the study will be assessed.
Baseline - day 1 - BCVA of both eyes will be tested on ETDRS charts. Non-contact IOP will be measured. Slit lamp anterior segment examination and fundus biomicroscopy of both eyes will be performed with artificial mydriasis. OCT of both eyes will be performed. Based on the examination results, patients' eligibility for the study will be assessed. Eligible patients will be randomised, and study medication will be given.
Week 4, Week 8, and Week 12 - adverse events connected to study drugs or study procedures will be assessed and study medication will be given.
Extension Visit Week 20 (group 1) or Week 24 (group 2) - After an initial loading phase of four monthly doses, the two groups differ in the length of the extended dosing intervals. Adverse events connected to study drugs or study procedures will be assessed. BCVA of both eyes will be tested on ETDRS charts. Slit lamp anterior segment examination and fundus biomicroscopy of both eyes will be performed in artificial mydriasis. OCT of both eyes will be performed. Study medication will be given.
Next treatment visit will be scheduled based on the disease activity on the OCT, the ocular examination findings and the BCVA in treat-and-extend regimen with minimal interval of 8 weeks and maximal interval of 16 weeks. The therapeutic interval in both groups may be extended or shortened in up to 4-week increments based on the patient's visual acuity and disease activity, as assessed by OCT evaluating the presence or absence of subretinal or intraretinal fluid or pigment epithelial detachment (PED) and on the presence of other signs of disease activity on the fundus examination (haemorrhage, hard exudates, etc.). It is up to the investigator to make the final decision on the treatment interval.
Follow-up Visits Week 20 to Week 56 - Treat-and-extend regimen. Adverse events connected to study drugs or study procedures will be assessed. BCVA of both eyes will be tested on ETDRS charts. Non-contact IOP will be measured. Slit lamp anterior segment examination and fundus biomicroscopy of both eyes will be performed in artificial mydriasis. OCT of both eyes will be performed. Study medication will be given. Next treatment visit will be scheduled based on the disease activity as described above (treat-and-extend regimen with possible up to 4-week adjustments).
End of Study Visit Week 44-56 - Adverse events assessment. BCVA of both eyes will be tested on ETDRS charts. Slit lamp anterior segment examination and fundus biomicroscopy of both eyes will be performed in artificial mydriasis. OCT of both eyes will be performed. OCTA of the study eye (SE) will be performed.
Study procedures:
OCT - performed on Spectralis OCT (Heidelberg Engineering GmbH, Heidelberg, Germany). CRT will be assessed from automatic retinal thickness analysis in 9 ETDRS subfields including the central subfield. 49 horizontal scans in the angle of 20x20° 123 um apart in High resolution mode with noise reduction set to ART=4 will be performed.
OCTA - performed on Spectralis OCT (Heidelberg Engineering GmbH, Heidelberg, Germany). 512 horizontal scans in the angle of 20x20° 11 um apart in High-speed mode with noise reduction set to ART=5 will be performed.
Disease activity assessment:
Based on the decision of the investigator. Shortening of the treatment interval is recommended when the BCVA decrease of more than 5 ETDRS letters is observed, in case of intra- or subretinal fluid or PED reappearance or increase on the OCT or when new haemorrhage or hard exudates are observed in the macula. Extension of the treatment interval is recommended in the absence of intra- and subretinal fluid and PED on the OCT with better or stable BCVA, or in case the BCVA and OCT findings are stable after 3 injections in the shortest possible interval.
Rescue therapy: Aflibercept may be given as a rescue therapy in case of patients with study drug related sight threatening adverse events or with worsening of BCVA and OCT findings even on the shortest treatment interval when resistance to study drug is suspected. Switch to rescue therapy must be consulted with and approved by principal investigator.
Eligibility
Inclusion criteria:
Active treatment naïve CNV (Type 1, Type 2, or Type 3) in the macula including fovea diagnosed on OCT and OCTA
BCVA between 70 to 35 ETDRS letters (approx. 20/40 to 20/200 Snellen equivalent) decrease in BCVA caused primarily by the CNV in the study eye
presence of intra- or subretinal fluid or PED in the central 1 mm of the macula on the OCT
patient capable of signing the informed consent
Exclusion Criteria:
Myocardial Infarction or Stroke in the last 3 months
Previous or current conditions of the study eye:
k. significant opacities of the ocular media in the study eye including cataract, which can interfere with BCVA assessment or OCT examination
n. diabetic retinopathy, diabetic macular edema or any other retinal vascular disease in the study eye
o. extraocular or periocular infection or inflammation (e.g. blepharitis, keratitis, conjunctivitis, scleritis, etc.) in any eye at the time of screening or baseline visit
p. any intraocular infection or inflammation in any eye during 12 weeks (84 days) before the screening visit
q. allergy or hypersensitivity to any component contained in the study drug
r. pregnant or breastfeeding women
Enrollment
Sex
Volunteers
Inclusion criteria
Active treatment naïve CNV (Type 1, Type 2, or Type 3) in the macula including fovea diagnosed on OCT and OCTA
BCVA between 70 to 35 ETDRS letters (approx. 20/40 to 20/200 Snellen equivalent) decrease in BCVA caused primarily by the CNV in the study eye
presence of intra- or subretinal fluid or PED in the central 1 mm of the macula on the OCT
patient capable of signing the informed consent
Exclusion criteria
Myocardial Infarction or Stroke in the last 3 months
Previous or current conditions of the study eye:
k. significant opacities of the ocular media in the study eye including cataract, which can interfere with BCVA assessment or OCT examination
n. diabetic retinopathy, diabetic macular edema or any other retinal vascular disease in the study eye
o. extraocular or periocular infection or inflammation (e.g. blepharitis, keratitis, conjunctivitis, scleritis, etc.) in any eye at the time of screening or baseline visit
p. any intraocular infection or inflammation in any eye during 12 weeks (84 days) before the screening visit
q. allergy or hypersensitivity to any component contained in the study drug
r. pregnant or breastfeeding women
Primary purpose
Allocation
Interventional model
Masking
100 participants in 2 patient groups
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Central trial contact
Martin Pencak, MD; Patrik Rajs, MD
Data sourced from clinicaltrials.gov
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