PDS with Ranibizumab vs. Intravitreal Ranibizumab for Diabetic Macular Edema

(Pagoda Trial)

Recruiting at 143 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

Trial Summary

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. ^{1 2 3 4 5}

Is 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. ^{1 2 3 4 6}

How 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. ^{3 4 5 7 8}

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.

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility 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

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

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

Treatment Details

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.

Participant Groups

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, 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 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 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 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 Arm Active Control 2 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.

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

Findings from Research

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]

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 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]

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]

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]

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]

References

1. United States 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. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Archway Randomized Phase 3 Trial of the Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Port delivery system: a novel drug delivery platform to treat retinal diseases. [2021]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Therapeutic Potential of the Ranibizumab Port Delivery System in the Treatment of AMD: Evidence to Date. [2020]

5. United States 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. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Management of Key Ocular Adverse Events in Patients Implanted with the Port Delivery System with Ranibizumab. [2022]

7. England 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. [2022]

8. England pubmed.ncbi.nlm.nih.gov

The Port Delivery System with ranibizumab: a new paradigm for long-acting retinal drug delivery. [2022]