PDS with Ranibizumab vs. Intravitreal Ranibizumab for Diabetic Macular Edema
(Pagoda Trial)
Recruiting in Palo Alto (17 mi)
+147 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Hoffmann-La Roche
Must not be taking: Antimitotics, Antimetabolites
Disqualifiers: Cancer, Stroke, Atrial fibrillation, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This study will evaluate the efficacy, safety, and pharmacokinetics of the PDS with Ranibizumab in participants with DME when treated every 24 weeks (Q24W) compared with intravitreal ranibizumab 0.5 mg every 4 weeks (Q4W).
The substudy will evaluate safety of re-implanting the updated PDS with ranibizumab and the refill-exchange procedures following re-implantation in participants with DME who were previously enrolled in the main Study, GR40550. Up to 100 participants from the main study will be enrolled and followed for a maximum of 72 weeks post-re-implantation in the substudy.
Do I have to stop taking my current medications for the trial?
The trial information does not specify if you need to stop taking your current medications. However, you cannot participate if you have used antimitotic or antimetabolite therapy within 30 days or if you are currently receiving systemic treatment for an active infection.
What data supports the effectiveness of this treatment for diabetic macular edema?
The Port Delivery System with ranibizumab (PDS) has shown effectiveness in treating neovascular age-related macular degeneration (nAMD) by providing continuous delivery of the drug, reducing the need for frequent injections. This suggests it may also be effective for diabetic macular edema, as both conditions involve similar mechanisms related to blood vessel growth in the eye.
12345Is the Port Delivery System with Ranibizumab safe for use in humans?
The Port Delivery System with Ranibizumab has been evaluated for safety in clinical trials for age-related macular degeneration, showing it can be safe for use in humans. However, like any medical treatment, it may have some side effects, and strategies have been developed to manage these potential issues.
12346How does the Port Delivery System with Ranibizumab differ from other treatments for diabetic macular edema?
The Port Delivery System with Ranibizumab is unique because it is a surgically implanted device that continuously releases the medication into the eye, reducing the need for frequent injections. This system maintains therapeutic drug levels over an extended period, potentially lowering the treatment burden compared to regular intravitreal injections.
34578Eligibility Criteria
This trial is for adults over 18 with Diabetic Macular Edema (DME) showing specific retina swelling, a certain vision score range, and controlled diabetes. It's not for those with recent severe heart or brain events, uncontrolled eye pressure or glaucoma, recent worsening of atrial fibrillation, uncontrolled blood pressure, or eye infections.Inclusion Criteria
I am 18 years old or older.
HbA1c level of ≤10% within 2 months prior to screening or at screening
My eye condition involves swelling in the center of my vision.
+3 more
Exclusion Criteria
I have active eye inflammation.
I do not have uncontrolled high eye pressure or glaucoma needing surgery during the study.
I was diagnosed with or my atrial fibrillation got worse in the last 6 months.
+4 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive intravitreal ranibizumab injections every 4 weeks initially, followed by PDS implant with refill-exchange procedures every 24 weeks
64 weeks
16 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
56 weeks
8 visits (in-person)
Substudy Follow-up
Participants are followed for safety of re-implanting the updated PDS with ranibizumab and the refill-exchange procedures
72 weeks
Participant Groups
The study compares two treatments: a Port Delivery System with Ranibizumab (PDS), given every 24 weeks versus standard ranibizumab injections into the eye every 4 weeks. The goal is to see if PDS can be as effective but less frequent.
5Treatment groups
Experimental Treatment
Active Control
Group I: Substudy: Cohort 2bExperimental Treatment1 Intervention
Participants who received an updated PDS implant, have \< 48 weeks post-re-implantation follow-up and one refill exchange visit in the main study, will undergo one refill-exchange procedure (ranibizumab 100 mg/mL) Q24W, post main study re-implantation visit.
Group II: Substudy: Cohort 2aExperimental Treatment1 Intervention
Participants who received an updated PDS implant, have \< 24 weeks post-re-implantation follow-up and no refill exchange visit in the main study, will undergo two refill-exchange procedures (ranibizumab 100 mg/mL) Q24W, post main study re-implantation visit.
Group III: Substudy: Cohort 1Experimental Treatment2 Interventions
Participants will undergo re-implantation with the updated PDS implant (pre-filled with ranibizumab 100 mg/mL) on Day 1 (or enrollment visit) and then will have two refill-exchanges (ranibizumab 100 mg/mL) Q24W up to 48 weeks.
Group IV: PDS ArmExperimental Treatment2 Interventions
Participants randomized to the PDS arm will receive intravitreal ranibizumab injection every 4 weeks (loading phase) and will then have the PDS implant (pre-filled with ranibizumab) surgically inserted. PDS implant refill-exchange procedures will be performed on a fixed interval every 24-weeks (Q24W) thereafter
Group V: Intravitreal ArmActive Control2 Interventions
Participants randomized to the intravitreal arm will receive intravitreal ranibizumab injection every 4 weeks until they receive the PDS implant (pre-filled with ranibizumab). PDS implant refill-exchange procedures will be performed on a fixed interval Q24W thereafter.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Retina Consultants of Orange CountyFullerton, CA
Cumberland Valley Retina AssociatesHagerstown, MD
Sierra Eye AssociatesReno, NV
Midwest Vision Research FoundationChesterfield, MO
More Trial Locations
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Who Is Running the Clinical Trial?
Hoffmann-La RocheLead Sponsor
References
The Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration: Results from the Randomized Phase 2 Ladder Clinical Trial. [2020]To evaluate the safety and efficacy of the Port Delivery System with ranibizumab (PDS) for neovascular age-related macular degeneration (nAMD) treatment.
Archway Randomized Phase 3 Trial of the Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration. [2022]To evaluate the safety and efficacy of the Port Delivery System with ranibizumab (PDS) for the treatment of neovascular age-related macular degeneration (nAMD).
Port delivery system: a novel drug delivery platform to treat retinal diseases. [2021]Retinal disease treatment delivery is mostly limited to intravitreal injections and slow-release injectable implants due to structural barriers in the eye, and carry associated adverse effects and relatively high treatment burden. The Port Delivery System with ranibizumab (PDS) is a novel drug delivery device that is surgically implanted into the vitreous cavity and allows for continuous release of the anti-vascular endothelial growth factor (anti-VEGF) ranibizumab, eliminating the need for frequent intravitreal injections while maintaining therapeutic intraocular drug levels to control disease activity. Investigations of PDS are summarized in this review.
Therapeutic Potential of the Ranibizumab Port Delivery System in the Treatment of AMD: Evidence to Date. [2020]Age-related macular degeneration (AMD) is one of the leading causes of blindness in older adults worldwide. The advent of intravitreal neutralization of vascular endothelial growth factor (VEGF) has revolutionized the management of patients with neovascular AMD, but current anti-VEGF therapies carry a high threshold of patient burden. The ranibizumab port delivery system (PDS) is an implanted, refillable reservoir that continuously supplies the anti-VEGF medication ranibizumab directly into the vitreous, eliminating the need for frequent intravitreal injections. It has most recently been evaluated in the Phase II LADDER trial demonstrating the efficacy and safety of the PDS, with Phase III trials currently underway. This review presents both the promise and drawbacks of the PDS in the treatment of AMD from the current literature.
Patient Preference and Treatment Satisfaction With a Port Delivery System for Ranibizumab vs Intravitreal Injections in Patients With Neovascular Age-Related Macular Degeneration: A Randomized Clinical Trial. [2022]The port delivery system (PDS) with ranibizumab has demonstrated noninferior and equivalent efficacy compared with monthly intravitreal injections of ranibizumab, an anti-vascular endothelial growth factor (VEGF) agent, in patients with neovascular age-related macular degeneration (nAMD), but evaluating patient preference is important to help inform clinical decision-making.
Management of Key Ocular Adverse Events in Patients Implanted with the Port Delivery System with Ranibizumab. [2022]To provide strategies for the management of key ocular adverse events (AEs) that may be encountered with the Port Delivery System with ranibizumab (PDS) in practice and provide recommendations that may mitigate such AEs based on clinical trial experiences and considerations from experts in the field.
The efficacy and safety of intravitreal injection of Ranibizumab as pre-treatment for vitrectomy in proliferative diabetic retinopathy with vitreous hemorrhage. [2022]Intravitreal injection of anti-vascular endothelial growth factor (VEGF) has become first line therapy for diabetic macular edema. This study evaluated the efficacy and safety of intravitreal injection of Ranibizumab (IVR) as pre-treatment for pars plana vitrectomy in proliferative diabetic retinopathy (PDR) patients with vitreous hemorrhage.
The Port Delivery System with ranibizumab: a new paradigm for long-acting retinal drug delivery. [2022]The Port Delivery System with ranibizumab (PDS) is an innovative intraocular drug delivery system designed for the continuous delivery of ranibizumab into the vitreous for 6 months and beyond. The PDS includes an ocular implant, a customized formulation of ranibizumab, and four dedicated ancillary devices for initial fill, surgical implantation, refill-exchange, and explantation, if clinically indicated. Ranibizumab is an ideal candidate for the PDS on account of its unique physicochemical stability and high solubility. Controlled release is achieved via passive diffusion through the porous release control element, which is tuned to specific drug characteristics to accomplish a therapeutic level of ranibizumab in the vitreous. To characterize drug release from the implant, release rate was measured in vitro with starting concentrations of ranibizumab 10, 40, and 100 mg/mL, with release of ranibizumab 40 and 100 mg/mL found to remain quantifiable after 6 months. Using a starting concentration of 100 mg/mL, active release rate at approximately 6 months was consistent after the initial fill and first, second, and third refills, demonstrating reproducibility between implants and between multiple refill-exchanges of the same implant. A refill-exchange performed with a single 100-µL stroke using the refill needle was shown to replace over 95% of the implant contents with fresh drug. In vitro data support the use of the PDS with fixed refill-exchange intervals of at least 6 months in clinical trials.