Extension Study for the Port Delivery System With Ranibizumab (Portal) (Portal)
Neovascular Age-Related Macular Degeneration
About this trial
This is an interventional treatment trial for Neovascular Age-Related Macular Degeneration
Eligibility Criteria
Inclusion Criteria:
- Previous enrollment in and completion of Study GX28228 (Ladder) or Study GR40548 (Archway), without early treatment or study discontinuation in either study OR Previous enrollment in Study WR42221 (Velodrome) and either not eligible to be randomized in Study WR42221 at Week 24 or completed the study (from the Q24W or Q36W arm)
- Ability and willingness to undertake all scheduled visits and assessments
- For women of childbearing potential: agreement to remain abstinent or use contraceptive measures
Exclusion Criteria:
- Pregnant or breastfeeding, or intending to become pregnant during the treatment period and for at least 28 days after the last intravitreal injection of ranibizumab or 1 year after the last Implant refill-exchange of ranibizumab
- History of other ocular diseases that give reasonable suspicion of a disease or condition that contraindicates the use of ranibizumab, that might affect interpretation of the results of the study or that renders the participant at high risk for treatment complications
- History of other diseases, metabolic dysfunction, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of ranibizumab or placement of the Implant and that might affect interpretation of the results of the study or that renders the participant at high risk of treatment complications
- Requirement for continuous use of any medications or treatments indicated in the "Prohibited Therapy"
Substudy
Inclusion Criteria
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures,
Patients must meet the following ocular criteria for the study eye for substudy entry:
- Diagnosis of exudative nAMD within 2 years prior to the enrollment visit
- Previous treatment with at least two anti-VEGF ITV injections (e.g., ranibizumab, bevacizumab, or aflibercept) for nAMD per standard of care within 6 months prior to the enrollment visit
- Demonstrated response to prior anti-VEGF ITV treatment since diagnosis, as evidenced at enrollment by the following:
Overall decrease in nAMD disease activity detected on SD-OCT AND Stable or improved best-corrected visual acuity (BCVA)
- All subtypes of nAMD lesions are permissible (i.e., type I, type II, type III, or mixed forms per optical coherence tomography (OCT) classification) 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 analysis and grading by the central reading center of FP and SD-OCT images.
Exclusion Criteria
Prior Ocular Treatments Study Eye
- History of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD
- Prior treatment with Visudyne, external-beam radiation therapy, or transpupillary thermotherapy
- Previous treatment with corticosteroid ITV injection
- Previous intraocular device implantation
- Previous laser (any type) used for AMD treatment
Either Eye
- Treatment with anti-VEGF agents other than ranibizumab within 1 month prior to the enrollment visit
- Prior participation in a clinical trial involving anti-VEGF drugs within 6 months prior to the enrollment visit, other than ranibizumab
CNV Lesion Charateristics Study Eye
- Subretinal hemorrhage that involves the center of the fovea, if the hemorrhage is greater than 0.5 disc area (1.27 mm2 ) in size at screening
- Subfoveal fibrosis or subfoveal atrophy
Either Eye
- CNV due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia
Concurrent Ocular Conditions Study Eye
- Retinal pigment epithelial tear
- Any concurrent intraocular condition (e.g., cataract, glaucoma, diabetic retinopathy, or epiretinal membrane) that would either require surgical intervention during the study to prevent or treat visual loss that might result from that condition or affect interpretation of study results
- Active intraocular inflammation (grade trace or above)
- History of vitreous hemorrhage
- History of rhegmatogenous retinal detachment
- History of rhegmatogenous retinal tears or peripheral retinal breaks within 3 months prior to the enrollment visit
- Aphakia or absence of the posterior capsule
- Previous violation of the posterior capsule is also an exclusion criterion unless it occurred as a result of yttrium-aluminum garnet (YAG) laser posterior capsulotomy in association with prior, posterior chamber intraocular lens implantation.
- Spherical equivalent of the refractive error demonstrating more than 8 diopters of myopia
- Preoperative refractive error that exceeds 8 diopters of myopia, for patients who have undergone prior refractive or cataract surgery in the study eye
- Intraocular surgery (including cataract surgery) within 3 months preceding the enrollment visit
- Uncontrolled ocular hypertension or glaucoma and any such condition the investigator determines may require a glaucoma-filtering surgery during a patient's participation in the study
- History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery
- History of corneal transplant
- History of prior vitrectomy surgery and absence of posterior capsule
Either Eye
- History of idiopathic or autoimmune-associated uveitis
- Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis
Concurrent Systemic Conditions
- Inability to comply with study schedule or procedures as described in the study protocol
- Uncontrolled blood pressure
- History of stroke within the last 3 months prior to informed consent
- Uncontrolled atrial fibrillation within 3 months of informed consent
- History of myocardial infarction within the last 3 months prior to informed consent
- History of other disease, metabolic dysfunction, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of ranibizumab or placement of the implant and that might affect interpretation of the results of the study or renders the patient at high risk of treatment complications in the opinion of the investigator
- Current systemic treatment for a confirmed active systemic infection
- Use of any systemic anti-VEGF agents
- Chronic use of oral corticosteroids
- Active cancer within 12 months of enrollment
- Previous participation in any non-ocular (systemic) disease studies of investigational drugs within 1 month preceding the informed consent (excluding vitamins and minerals)
- Use of antimitotic or antimetabolite therapy within 30 days or 5 elimination half-lives of the enrollment visit
- History of albinism
- Pregnant or breastfeeding, or intending to become pregnant during the treatment period and for at least 28 days after the last ITV injection of ranibizumab or 1 year after the last implant refill-exchange of ranibizumab
Sites / Locations
- Barnet Dulaney Perkins Eye Center
- Retinal Research Institute, LLC
- Associated Retina Consultants
- Arizona Retina and Vitreous Consultants
- Retinal Consultants of Arizona
- California Retina Consultants
- Retina-Vitreous Associates Medical Group
- The Retina Partners
- Jacobs Retina center at the Shiley eye Institute UCSD
- Jules Stein Eye Institute/ UCLA
- N CA Retina Vitreous Assoc
- Retina Consultants, San DiegoRecruiting
- Retinal Consultants Med Group
- West Coast Retina Medical Group
- UCSF; Ophthalmology
- Orange County Retina Med Group
- California Retina Consultants
- Southwest Retina Consultants
- Eye Center of Northern CO
- Colorado Retina Associates, PC
- Retina Group of New England
- Florida Eye Microsurgical Inst
- National Ophthalmic Research Institute
- Florida Eye Associates
- Retina Care Specialists
- Retina Specialty Institute
- Fort Lauderdale Eye Institute
- Retina Vitreous Assoc of FL
- Southern Vitreoretinal Assoc
- Retina Associates of Florida, LLC
- Southeast Retina Center
- Georgia Retina PC
- Illinois Retina Associates
- University Retina and Macula Associates, PC
- Wolfe Eye Clinic
- Retina Associates
- Retina Associates of Kentucky
- Paducah Retinal Center
- Maine Eye Center
- The Retina Care Center
- Johns Hopkins Med; Wilmer Eye Inst
- Retina Group of Washington
- Retina Specialists
- Ophthalmic Consultants of Boston
- Associated Retinal Consultants
- Foundation for Vision Research
- VitreoRetinal Surgery, PLLC.; DBA Retina Consultants of Minnesota
- Midwest Vision Research Foundation
- The Retina Institute - Chesterfield
- Sierra Eye Associates
- Envision Ocular, LLC
- Retina Associates of NJ
- University of New Mexico; School of Med
- Long Is. Vitreoretinal Consult
- Retina Vit Surgeons/Central NY
- Ophthalmic Consultants of Long Island
- Retina Assoc of Western NY
- Char Eye Ear &Throat Assoc
- Cincinnati Eye Institute
- The Cleveland Clinic Foundation
- OSU Eye Physicians & Surgeons
- Retina Vitreous Center
- Retina NorthwestRecruiting
- Oregon HSU; Casey Eye Institute
- Mid Atlantic Retina - Wills Eye Hospital
- Palmetto Retina Center, LLC
- Palmetto Retina Center
- Charles Retina Institute
- Tennessee Retina PC
- Texas Retina Associates
- Austin Retina Associates
- Austin Clinical Research LLC
- Texas Retina Associates
- Med Center Ophthalmology Assoc
- Retina Consultants of Texas
- Retina Associates of Utah, PLLC
- Rocky Mountain Retina
- Wagner Kapoor Institute
- Retina Center Northwest
- Spokane Eye Clinical Research
- Centro Oftalmológico Dr. Charles S.A.Recruiting
- OftalmosRecruiting
- Grupo Laser VisionRecruiting
- Eyeclinic Albury WodongaRecruiting
- Eye and Retina ConsultantsRecruiting
- LKH-Univ.Klinikum Graz; Universitäts-AugenklinikRecruiting
- Medizinische Universität Wien; Universitätsklinik für Augenheilkunde und OptometrieRecruiting
- UZ Leuven GasthuisbergRecruiting
- Botelho Hospital da VisaoRecruiting
- Retina ClinicRecruiting
- Universidade Federal de Sao Paulo - UNIFESP*X; OftalmologiaRecruiting
- Instituto da Visão IPEPORecruiting
- Universitätsklinikum Ulm, Augenklinik und PoliklinikRecruiting
- Rambam Medical Center; OpthalmologyRecruiting
- Hadassah MC; OphtalmologyRecruiting
- Meir Medical Center; OphtalmologyRecruiting
- Rabin MC; OphtalmologyRecruiting
- Tel Aviv Sourasky MC; OphtalmologyRecruiting
- Hospital Universitario Puerta de Hierro; Servicio de oftalmologiaRecruiting
- Oftalvist ValenciaRecruiting
- Hospital dos de maig; servicio de oftalmologiaRecruiting
- Universitätsspital Basel Augenklinik KlinikRecruiting
- Inselspital Bern Ophthalmologische KlinikRecruiting
- Vista Klinik Ophthalmologische KlinikRecruiting
- Fondation Asile Des Aveugles ? Jules Gonin Eye HospitalRecruiting
- Stadtspital Triemli Ophthalmologische Klinik
- Changhua Christian Hospital; Department of OphthalmologyRecruiting
- Kaohsiung Medical University Chung-Ho Memorial Hospital; OphthalmologyRecruiting
- Taipei Veterans General Hospital; OphthalmologyRecruiting
- Chang Gung Medical Foundation - Linkou; OphthalmologyRecruiting
- National Taiwan University Hospital; OphthalmologyRecruiting
- Royal Liverpool University Hospital; St Paul's Clinical Eye Research CentreRecruiting
- Moorfields Eye Hospital NHS Foundation TrustRecruiting
- Kings College Hospital NHS Foundation TrustRecruiting
- Royal Victoria InfirmaryRecruiting
- Sunderland Eye InfirmaryRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
PDS Implant Cohort 1 (US only)
PDS Implant Cohort 2 (US only)
PDS Implant Cohort 3 (US only)
PDS Implant Cohort 4 (US only)
PDS Implant Cohort 5 (ex-US only)
PDS Implant Cohort 6 (ex-US only)
PDS Implant Cohort 7 (ex-US only)
Participants with PDS implant from Study GX28228 treated with refill-exchanges of 100 mg/mL ranibizumab Q24W. Participants will switch to an every 12 weeks (Q12W) visit schedule from Week 168 to Week 240. Eligible participants from Study GX28228 will be enrolled upon completion of their final visit.
Participants with PDS implant from Study GR40548 treated with refill-exchanges of 100 mg/mL ranibizumab Q24W. Participants will switch to an every 12 weeks (Q12W) visit schedule from Week 144 to Week 240. Eligible participants from Study GR40548 will be enrolled upon completion of their final visit.
Participants in the intravitreal ranibizumab arm of Study GX28228 who will receive the PDS implant upon study entry and refill-exchanges of 100 mg/mL ranibizumab Q24W. Participants will switch to an every 12 weeks (Q12W) visit schedule from Week 168 to Week 240. Eligible participants from Study GX28228 will be enrolled upon completion of their final visit.
Participants in the intravitreal ranibizumab arm of Study GR40548 who will receive the PDS implant upon study entry and refill-exchanges of 100 mg/mL ranibizumab Q24W. Participants will switch to an every 12 weeks (Q12W) visit schedule from Week 144 to Week 240. Eligible participants from Study GR40548 will be enrolled upon completion of their final visit.
Participants from Study WR42221 who completed Week 24 but were not eligible to be randomized within WR42221 and who will be treated with refill-exchanges of ranibizumab 100 mg/mL Q24W
Participants from Study WR42221 randomized to the Q24W arm, who will continue to be treated with refill-exchanges of ranibizumab 100 mg/mL Q24W
Participants from Study WR42221 randomized to the Q36W arm, who will continue to be treated with refill-exchanges of ranibizumab 100 mg/mL Q36W