Neovascular Age-Related Macular Degeneration (AMD) MedDRA version: 20.0 Level: PT Classification code 10071129 Term: Neovascular age-related macular degeneration System Organ Class: 10015919 - Eye disorders
Conditions
Sponsors
F. Hoffman-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: General inclusion criteria •Age >=50 years, at time of signing Informed Consent Form •For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures during the treatment period and for at least 3 months after the final intravitreal injection of ranibizumab or aflibercept, or 1 year after the last implant refill of ranibizumab Ocular Inclusion Criteria •Initial diagnosis of nAMD within 9 months prior to the screening visit •Previous treatment with at least three anti- vascular endothelial growth factor (VEGF) intravitreal injections for nAMD per standard of care within 6 months prior to the screening visit •Demonstrated response to prior anti-VEGF intravitreal treatment since diagnosis, as evidenced by the following: a) Overall decrease in nAMD disease activity detected on SD-OCT, as assessed by the investigator and confirmed by the central reading center and b) Stable or improved BCVA at randomization •Availability of historical visual acuity data obtained at or after nAMD diagnosis and prior to the first anti-VEGF treatment for nAMD •Availability of historical spectral-domain optical coherence tomography (SD-OCT) image data obtained at or after nAMD diagnosis and prior to the first anti-VEGF treatment for nAMD •BCVA of 34 letters or better (20/200 or better approximate Snellen equivalent), using Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters at screening and randomization visits •With any subtype of nAMD lesions (i.e., type I, type II, type III, or mixed forms per OCT classification, including polypoidal choroidal vasculopathy and retinal angiomatous proliferation). Exudative nAMD lesions at the time of diagnosis must involve the macula (6-mm diameter centered at the fovea) •Sufficiently clear ocular media and adequate pupillary dilation to allow for clinical examination and analysis and grading by the central reading center of fundus photography (FP), fluorescein angiography (FA), fundus autofluorescence (FAF) image, and SD-OCT images 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 56 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 504
Exclusion criteria
Exclusion criteria: Prior Ocular Treatment Study Eye •History of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD •Prior pars plana vitrectomy surgery •Prior treatment with Visudyne®, external-beam radiation therapy, or transpupillary thermotherapy • corticosteroid intravitreal injection •Previous intraocular device implantation •Previous intraocular surgery within 3 mths of randomization •Previous laser used for AMD or diabetic retinopathy treatment •History of vitreous hemorrhage, rhegmatogenous retinal detachment •Concurrent conjunctival, Tenon's capsule, and/or scleral condition in the supero-temporal quadrant of the eye •History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery, corneal transplant, conjunctival surgery in the superotemporal quadrant Either Eye •History of a severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the ranibizumab or aflibercept injections, study-related procedure preparations, dilating drops, or any of the anesthetic and antimicrobial preparations used by a subject •Any contraindication to aflibercept •Prior participation in a clinical trial involving any anti-VEGF drugs within 6 mths prior to the randomization visit •Prior treatment with brolucizumab, external-beam radiation therapy or brachytherapy Macular neovascularization (MNV) (choroidal neovascularization [CNV]) Lesion Characteristics Study Eye •Subretinal hemorrhage that involves the center of the fovea •Subfoveal fibrosis or subfoveal atrophy Either Eye •CNV due to other causes, such as ocular histoplasmosis, trauma, central serous chorio-retinopathy, or pathologic myopia •CNV masquerading lesions Concurrent Ocular Conditions Study Eye •Subfoveal and/or juxtafoveal retinal pigment epithelial tear •Scleral pathology in the superotemporal quadrant •Conjunctival pathologies in the superotemporal quadrant •Any concurrent intraocular condition •Active intraocular inflammation (grade trace or above) •Rhegmatogenous retinal tears or peripheral retinal breaks on depressed fundus exam that are untreated, or treated within 3 mths prior to the randomization visit •Aphakia or absence of the posterior capsule •Previous violation of the posterior capsule •Spherical equivalent of the refractive error demonstrating more than 8 diopters of myopia or evidence of pathologic myopia on depressed fundus exam •Preoperative refractive error that exceeds 8 diopters of myopia •Spherical equivalent of the refractive error demonstrating more than 5 diopters of hyperopia •Preoperative refractive error that exceeds 5 diopters of hyperopia •Uncontrolled ocular hypertension or glaucoma and any such condition the investigator determines may require a glaucoma-filtering surgery during a subject's participation in the study •History or presence of severe posterior blepharitis, recurrent chalazia or hordeolum, severe dry eye syndrome, or severe allergic conjunctivitis •Ectropion, entropion, in growing lashes, or other impairment of the upper or lower eyelid impacting lid functionality needed to protect the ocular surface from exposure •Trichiasis, Corneal neuropathy, Lagophthalmos or incomplete blink, Active or history of facial nerve palsy/paresis Non-Study (Fellow) Eye •BCVA of hand motion or worse •No physical presence of non-study eye •Legally blind in the subject’s relevant jurisdiction Either Eye •Any active or history of uveitis •Active or history of keratitis, scleritis,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To evaluate the effectiveness of the Port Delivery System (PDS) refilled with ranibizumab every 36 weeks (PDS Q36W) compared with aflibercept intravitreal injections administered per a treat-and-extend strategy (aflibercept T&E) according to (1) change in visual acuity and (2) treatment burden;Secondary Objective: •To evaluate the effectiveness of PDS Q36W compared with aflibercept T&E based on (1) best-corrected visual acuity (BCVA) score at end of study or change to BCVA score, (2) change in center point thickness (CPT) and center subfield thickness (CST) •To evaluate the proportion of subjects in PDS group not needing supplemental intravitreal treatment •To evaluate the safety of PDS Q36W and aflibercept T&E •To evaluate the PDS device and PDS procedures-related safety ;Primary end point(s): 1.Change from baseline in BCVA score averaged over Weeks 76 (or 78*) and 80, as assessed using the ETDRS visual acuity chart at a starting distance of 4 meters 2.Treatment burden as assessed by the treatment frequency up to Week 80 ;Timepoint(s) of evaluation of this end point: 1. Baseline, Week 76 and Week 80 2. Up to Week 80 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Proportion of subjects with BCVA score of 69 letters (approximate 20/40 Snellen equivalent) or better averaged over Week 76 (Week 78 for some subjects) and Week 80 2.Proportion of subjects with BCVA score of 38 letters (approximate 20/200 Snellen equivalent) or worse averaged over Weeks 76 (or 78) and 80 3.Proportion of subjects who lose 37 days after implantation surgery) 10.Incidence and severity of adverse device effects with PDS Q36W 11.Incidence, causality, severity, and duration of anticipated serious adverse device effects with PDS Q36W ;Timepoint(s) of evaluation of this end point: 1-3. At Weeks 78 and 80 4-5. Baseline and Week 80 6. Up to approximately 40 months 7-8. Up to approximately 40 months 9. During the postoperative period (= 37 days of initial implantation) and follow-up period (> 37 days after implantation surgery) 10-11. Up to approximately 40 months | — |
Countries
Argentina, Austria, Brazil, Canada, Chile, Czechia, Denmark, Finland, France, Germany, Greece, Hong Kong, Hungary, Ireland, Israel, Italy, Netherlands, Norway, Poland, Portugal, Singapore, Spain, Switzerland, Thailand, United Arab Emirates, United Kingdom
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffman-La Roche Ltd
Outcome results
None listed