PDS Implant with Ranibizumab 100 mg/mL: Will be administered as per the schedule described in individual arm
Study summary
This study will evaluate the long-term safety and tolerability of the Port Delivery System with ranibizumab (PDS) (100 mg/mL) in participants with neovascular age-related macular degeneration (nAMD) who have either completed Phase II Study GX28228 (Ladder), Phase III Study GR40548 (Archway), Phase IIIb Study WR42221 (Velodrome), or completed Week 24 visit in Study WR42221 but were not eligible to be randomized in WR42221.
Eligibility
Sex
ALL
Min age
50 Years
Max age
—
Healthy volunteers
No
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"
Sub-study 1
Inclusion Criteria
\- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures
Participants 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 participants 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
Sub-study 2
Inclusion Criteria:
* Having experienced septum dislodgement in the original implant while in the main study or after exiting the main study Ocular Inclusion Criteria for Study Eye
* Sufficiently clear ocular media and adequate pupillary dilation to allow for analysis and grading by central reading center
Exclusion Criteria (Cohort 1 only):
Concurrent Ocular Conditions-Study Eye
* Any ocular condition that may render the patient at high risk for surgical or treatment complications
* Intraocular surgery (including cataract surgery) within 1 month preceding the enrollment visit
* Any use of medicated intraocular implants (other than the PDS implant), at any time prior to enrollment
* History of rhegmatogenous retinal tears or peripheral retinal breaks within 3 months prior to the enrollment visit
* Any concurrent ocular condition that would require surgical intervention during the study to prevent or treat visual loss
* Concurrent conjunctival, Tenon's capsule, and/or scleral condition in the supero-temporal quadrant of the eye (e.g., scarring, thinning, mass) that may affect the refill-exchange procedure of the PDS implant
* Ongoing ocular complications that might affect participant safety
Concurrent Ocular Conditions-Either Eye
* Suspected or active ocular or periocular infection
* Any history of uveitis
* Active blepharitis
Concurrent Systemic Conditions
* Recent history (in the last 3 months prior to enrollment) of other disease, other non-diabetic metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a condition that contraindicates the use of ranibizumab or surgical placement of the PDS implant; that might affect interpretation of the results of the study; or that renders the participant at high risk for treatment complications
* Active cancer within the last 12 months, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or prostate cancer
* Current systemic treatment for a confirmed active systemic infection - Participation in an investigational trial that involves treatment with any drug or device (with the exception of vitamins and minerals or enrollment in the main study GR40549) within 6 months prior to enrollment.
* Use of antimitotic or antimetabolite therapy within 30 days or 5 elimination half-lives.
Primary outcome measure(s)
Incidence and Severity of Ocular and Systemic (Non-Ocular) Adverse Events (AEs) — Baseline up to Week 240
Incidence, Severity, and Duration of Adverse Event of Special Interest (AESIs) — Baseline up to Week 240
Incidence, Severity, and Duration of PDS-Associated Ocular AESIs During the Postoperative Period (Up to 37 days of Initial Implantation) and Follow-Up Period (>37 days After Implantation Surgery) for Participants who Receive the PDS Implant in the Study — Baseline up to Week 240
Incidence and Severity of Adverse Device Effects — Baseline up to Week 240
Incidence, Causality, Severity, And Duration Of Anticipated Serious Adverse Device Effects — Baseline up to Week 240
Sub-study 1: Rate of Vitreous Hemorrhage Secondary to Choroidal Bleeding That Does not Resolve by the Week 4 Visit After Implant Insertion Surgery. — Baseline to Week 4
Sub-study 2: Number of Participants with Ocular and Systemic (Non-ocular) Adverse Events (AEs) and Severity of These AEs — Baseline to Week 72
Sub-study 2: Number of Participants with Adverse Events of Special Interests (AESIs) and Severity of AESIs — Baseline to Week 72
Sub-study 2: Duration of AESIs — Baseline to Week 72
Sub-study 2: Number of participants with Ocular AESIs and Severity of Ocular AESIs During the Post-operative Period — Up to Day 37 post re-implantation
Sub-study 2: Number of participants with Ocular AESIs and Severity of Ocular AESIs During the Follow-up Period — > 37 days post re-implantation (up to approximately Week 72)
Sub-study 2: Duration of Ocular AESIs During the Post-operative Period — Up to Day 37 post re-implantation
Sub-study 2: Duration of Ocular AESIs During the Follow-up Period — > 37 days post re-implantation (up to approximately Week 72)
Sub-study 2: Number of Participants with Adverse Device Effects (ADEs) and Severity of ADEs — Baseline to Week 72
Sub-study 2: Number of Participants with Anticipated Serious ADEs and Severity of Anticipated Serious ADEs — Baseline to Week 72
Sub-study 2: Duration of Anticipated Serious ADEs — Baseline to Week 72
Sub-study 2: Number of Device Deficiencies — Baseline to Week 72
Trial sites (165)
Facility
City
Region
Status
Retinal Research Institute, LLC
Phoenix
Arizona
Completed
Arizona Retina and Vitreous Consultants
Phoenix
Arizona
Completed
Barnet Dulaney Perkins Eye Center
Phoenix
Arizona
Active Not Recruiting
Associated Retina Consultants
Phoenix
Arizona
Completed
Retinal Consultants of Arizona
Phoenix
Arizona
Completed
California Retina Consultants
Bakersfield
California
Completed
Retina-Vitreous Associates Medical Group
Beverly Hills
California
Completed
The Retina Partners
Encino
California
Active Not Recruiting
Jacobs Retina center at the Shiley eye Institute UCSD
La Jolla
California
Completed
Jules Stein Eye Institute/ UCLA
Los Angeles
California
Completed
N CA Retina Vitreous Assoc
Mountain View
California
Completed
Retina Consultants, San Diego
Poway
California
Completed
Retinal Consultants Med Group
Sacramento
California
Completed
West Coast Retina Medical Group
San Francisco
California
Completed
UCSF
San Francisco
California
Completed
Orange County Retina Med Group
Santa Ana
California
Active Not Recruiting
California Retina Consultants
Santa Barbara
California
Completed
Southwest Retina Consultants
Durango
Colorado
Completed
Eye Center of Northern CO
Fort Collins
Colorado
Completed
Colorado Retina Associates, PC
Lakewood
Colorado
Completed
Retina Group of New England
Waterford
Connecticut
Completed
Florida Eye Microsurgical Inst
Boynton Beach
Florida
Completed
National Ophthalmic Research Institute
Fort Myers
Florida
Completed
Florida Eye Associates
Melbourne
Florida
Completed
Retina Care Specialists
Palm Beach Gardens
Florida
Completed
Retina Specialty Institute
Pensacola
Florida
Completed
Fort Lauderdale Eye Institute
Plantation
Florida
Completed
Retina Vitreous Assoc of FL
St. Petersburg
Florida
Active Not Recruiting
Southern Vitreoretinal Assoc
Tallahassee
Florida
Active Not Recruiting
Retina Associates of Florida, LLC
Tampa
Florida
Completed
Southeast Retina Center
Augusta
Georgia
Completed
Georgia Retina PC
Marietta
Georgia
Withdrawn
Illinois Retina Associates
Joliet
Illinois
Completed
University Retina and Macula Associates, PC
Oak Forest
Illinois
Completed
Wolfe Eye Clinic
West Des Moines
Iowa
Completed
Retina Associates
Lenexa
Kansas
Completed
Retina Associates of Kentucky
Lexington
Kentucky
Completed
Paducah Retinal Center
Paducah
Kentucky
Withdrawn
Maine Eye Center
Portland
Maine
Completed
The Retina Care Center
Baltimore
Maryland
Completed
+ 125 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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