PDS with Ranibizumab vs. Intravitreal Ranibizumab for Diabetic Macular Edema

(Pagoda Trial)

Recruiting at 96 trial locations

Overseen By Reference Study ID Number: GR40550 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must not be taking: Antimitotics, Antimetabolites

Disqualifiers: Cancer, Stroke, Atrial fibrillation, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 24

Duration: 64 weeks

634 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments for diabetic macular edema (DME), a condition causing blurry vision due to fluid buildup in the eye. One group receives a new device called a Port Delivery System (PDS), which slowly releases the medication ranibizumab every six months. The other group receives monthly eye injections of the same medication, known as intravitreal ranibizumab. The researchers aim to determine if the PDS is as safe and effective as regular injections. People with diabetes experiencing blurry vision from DME might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the Port Delivery System (PDS) with ranibizumab is generally well-tolerated. The risk of complications is similar to other eye implants, making it about as safe as other treatments involving eye devices.

For ranibizumab injections into the eye, past patients have generally tolerated it well. Some side effects have been reported, but they are usually mild and manageable. This treatment is already approved for other eye conditions, indicating its safety for patients.

Overall, both treatments have strong evidence supporting their safety. They have been tested in many people and are considered to have a reasonable safety profile. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for diabetic macular edema because they offer new ways to deliver the medication. The Port Delivery System (PDS) with ranibizumab is a unique implant that slowly releases the drug over time, reducing the need for frequent eye injections compared to the standard treatment of regular intravitreal injections. This means patients might experience fewer visits to the clinic and potentially more consistent drug delivery. Additionally, the PDS can be refilled periodically, which could lead to better long-term control of the condition. This innovation in drug delivery is a promising advancement for those managing diabetic macular edema.

What evidence suggests that this trial's treatments could be effective for diabetic macular edema?

In previous studies, the Port Delivery System (PDS) with ranibizumab showed promising results for treating diabetic macular edema (DME). Research indicates that patients using the PDS experienced significant improvements in their eye condition, with many achieving better vision than those who did not receive this treatment. Long-term data suggests the PDS maintains its effectiveness over time, reducing the need for frequent eye injections. Additionally, ranibizumab delivered through PDS was well-tolerated, with a safety profile similar to traditional methods. In this trial, participants will be randomized to receive either the PDS with ranibizumab or intravitreal ranibizumab injections. These findings support the potential of PDS with ranibizumab as an effective option for managing DME. ^{3 4 6 7 8}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

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

HbA1c level of ≤10% within 2 months prior to screening or at screening

My eye condition involves swelling in the center of my vision.

I have been diagnosed with diabetes (Type 1 or Type 2).

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Intravitreal Ranibizumab
• Port Delivery System with Ranibizumab

Trial Overview 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.

How Is the Trial Designed?

Group I: Substudy: Cohort 2b Experimental Treatment 1 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, regardless of whether the refill exchange was administered or the visit was missed, will undergo one refill-exchange procedure (ranibizumab 100 mg/mL) Q24W, post main study re-implantation visit.

Group II: Substudy: Cohort 2a Experimental Treatment 1 Intervention

Participants who received an updated PDS implant, have \< 24 weeks post-re-implantation follow-up and no scheduled 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 1 Experimental Treatment 2 Interventions

Participants will undergo re-implantation with the updated PDS implant (pre-filled with ranibizumab 100 milligrams per milliliter \[mg/mL\]) 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 Arm Experimental Treatment 2 Interventions

Participants randomized to the PDS arm will receive IVT ranibizumab injection Q4W (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 Q24W thereafter.

Group V: Intravitreal Arm Active Control 2 Interventions

Participants randomized to the intravitreal arm will receive IVT ranibizumab injection Q4W until they receive the PDS implant (pre-filled with ranibizumab). PDS implant refill-exchange procedures will be performed on a fixed interval Q24W thereafter.

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Published Research Related to This Trial

The ranibizumab port delivery system (PDS) offers a continuous supply of the anti-VEGF medication ranibizumab for treating age-related macular degeneration (AMD), significantly reducing the need for frequent injections, which can be burdensome for patients.

The Phase II LADDER trial has shown that the PDS is both effective and safe for managing neovascular AMD, with ongoing Phase III trials to further evaluate its benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Potential of the Ranibizumab Port Delivery System in the Treatment of AMD: Evidence to Date. Chen, ER., Kaiser, PK.[2020]

Intravitreal injection of Ranibizumab (IVR) before vitrectomy in patients with proliferative diabetic retinopathy (PDR) and vitreous hemorrhage was found to be safe and effective, with no new tractional retinal detachments occurring in treated patients.

The study demonstrated that IVR significantly reduced VEGF levels in the aqueous humor, improving intraoperative conditions, which suggests that preoperative IVR can enhance surgical outcomes for PDR patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of intravitreal injection of Ranibizumab as pre-treatment for vitrectomy in proliferative diabetic retinopathy with vitreous hemorrhage. Li, S., Yang, Y., Zou, J., et al.[2022]

In a phase 3 clinical trial involving 415 patients with neovascular age-related macular degeneration (nAMD), the port delivery system (PDS) with ranibizumab showed similar treatment satisfaction compared to monthly intravitreal injections, indicating both methods are effective.

A significant majority (93.2%) of patients using the PDS preferred this method over previous intravitreal injections, suggesting that PDS could be a favorable alternative for long-term treatment in nAMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Chang, MA., Kapre, A., Kaufman, D., et al.[2022]

The Port Delivery System (PDS) with ranibizumab is a refillable ocular drug delivery system that can lead to various ocular adverse events (AEs) such as conjunctival retraction and endophthalmitis, but these AEs are generally manageable and do not significantly hinder patient outcomes.

Surgeons should be trained to recognize and manage these potential AEs early, emphasizing the importance of optimal surgical techniques and continuous refinement of the procedure to enhance safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Key Ocular Adverse Events in Patients Implanted with the Port Delivery System with Ranibizumab. Awh, CC., Barteselli, G., Makadia, S., et al.[2022]

The Port Delivery System (PDS) allows for continuous delivery of ranibizumab into the eye for at least 6 months, providing a stable and effective treatment option for conditions requiring this medication.

In vitro studies demonstrated that the PDS maintains consistent drug release rates over time, with over 95% of the implant contents being replaceable during refill-exchanges, indicating its reliability for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Port Delivery System with ranibizumab: a new paradigm for long-acting retinal drug delivery. Ranade, SV., Wieland, MR., Tam, T., et al.[2022]

The Port Delivery System (PDS) for ranibizumab offers a continuous drug release mechanism that significantly reduces the need for frequent intravitreal injections, which are typically burdensome for patients with retinal diseases.

Preliminary studies and phase I-III trials indicate that PDS maintains effective therapeutic levels of ranibizumab, achieving visual and anatomical outcomes comparable to standard monthly injections, thus showing promise for improving treatment adherence and patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Port delivery system: a novel drug delivery platform to treat retinal diseases. Khanani, AM., Aziz, AA., Weng, CY., et al.[2021]

The Port Delivery System (PDS) with ranibizumab for treating neovascular age-related macular degeneration (nAMD) was well tolerated and showed a dose-dependent response, with the 100 mg/ml dose providing visual and anatomical outcomes similar to monthly injections of ranibizumab, but with fewer treatments required.

Patients receiving the PDS had a median time to first implant refill of up to 15 months, indicating a significant reduction in treatment frequency compared to traditional monthly injections, which could lessen the treatment burden for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration: Results from the Randomized Phase 2 Ladder Clinical Trial. Campochiaro, PA., Marcus, DM., Awh, CC., et al.[2020]

The Port Delivery System (PDS) with ranibizumab demonstrated noninferior and equivalent efficacy to monthly ranibizumab injections for treating neovascular age-related macular degeneration (nAMD), with 98.4% of patients not requiring supplemental treatment during the first 24 weeks.

However, the PDS Q24W arm experienced a higher rate of ocular adverse events (19.0%) compared to the monthly ranibizumab arm (6.0%), including serious complications like endophthalmitis and retinal detachments, mostly occurring within the first month after implantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Archway Randomized Phase 3 Trial of the Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration. Holekamp, NM., Campochiaro, PA., Chang, MA., et al.[2022]

Citations

1. jamanetwork.com jamanetwork.com/journals/jamaophthalmology/fullarticle/2830898

Continuous Ranibizumab via Port Delivery System vs ... Long-term outcomes of ranibizumab therapy for diabetic macular edema: the 36-month results from two phase III trials: RISE and RIDE.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11886866/

Port Delivery System With Ranibizumab vs Monitoring in ... In this randomized clinical trial, substantially more participants receiving PDS vs monitoring achieved at least 2-step DRSS level improvement and avoided CI- ...

3. roche.com roche.com/media/releases/med-cor-2024-07-18

New data for Roche's Susvimo demonstrates sustained ... A study to evaluate the efficacy, safety and pharmacokinetics of the Port Delivery System with ranibizumab in participants with diabetic ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2666914523001744

Long-term Outcomes of Faricimab and Port Delivery ... Josic, et al. Five-year outcomes after initial aflibercept, bevacizumab, or ranibizumab treatment for diabetic macular edema (Protocol T Extension Study).

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04108156

NCT04108156 | A Study to Evaluate Efficacy, Safety & ... This study will evaluate the efficacy, safety, and Pharmacokinetics (PK) of the PDS with ranibizumab in participants with DME when treated every 24 weeks (Q24W) ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40048178/

The Pavilion Randomized Clinical Trial At 1 year, PDS Q36W resulted in substantially more participants achieving at least a 2-step DRSS improvement and a reduced risk of developing CI-DME, PDR, or ...

7. jamanetwork.com jamanetwork.com/journals/jamaophthalmology/fullarticle/2830899

Port Delivery System With Ranibizumab vs Monitoring in ... This randomized clinical trial evaluates whether the Port Delivery System with ranibizumab, compared with monitoring, improves Diabetic ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39090513

Systematic Literature Reviews Comparing the Long-Term ... The rates of complications reported in phase III clinical trials for the PDS were within the ranges reported for other ocular implants that cross the sclera.