PDS Implant with Ranibizumab for Age-Related Macular Degeneration

(Portal Trial)

Recruiting at 167 trial locations

Overseen By Reference Study ID Number: GR40549 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must be taking: Anti-VEGF injections

Must not be taking: Systemic anti-VEGF, Oral corticosteroids

Disqualifiers: Pregnancy, Ocular diseases, Uncontrolled hypertension, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 24

Duration: Up to 240 weeks

1000 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that participants do not use certain medications, as there is a 'Prohibited Therapy' list. If you are on any continuous medications, you may need to stop them if they are on this list. Please consult with the trial coordinators for specific details.

What data supports the effectiveness of the drug Ranibizumab for age-related macular degeneration?

Research shows that Ranibizumab is effective in treating age-related macular degeneration, with studies indicating positive outcomes over 5 to 7 years of treatment. The Port Delivery System with Ranibizumab (Susvimo) is being developed to address unmet needs in this area, suggesting ongoing improvements in treatment delivery. ^{1 2 3 4 5}

Is the PDS Implant with Ranibizumab safe for humans?

Ranibizumab, also known as Lucentis or Susvimo, has been studied for safety in treating age-related macular degeneration. Research shows that it is generally safe, with no significant increase in serious side effects compared to those not receiving the treatment. ^{6 7 8 9 10}

How is the Port Delivery System with ranibizumab different from other treatments for age-related macular degeneration?

The Port Delivery System with ranibizumab is unique because it allows for continuous delivery of the drug, reducing the need for frequent eye injections compared to traditional treatments that require monthly injections. ^{3 9 11 12 13}

What is the purpose of this trial?

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.

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for patients with neovascular age-related macular degeneration who completed certain previous studies (Ladder, Archway, or Velodrome) without early discontinuation. Participants must be able to attend all visits and assessments. Women of childbearing potential must agree to use contraception or remain abstinent.

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)

I can attend all appointments and follow study procedures.

For women of childbearing potential: agreement to remain abstinent or use contraceptive measures

Exclusion Criteria

I am not pregnant, breastfeeding, nor planning to become pregnant soon.

I am not on any medications listed in the 'Prohibited Therapy'.

I don't have eye diseases that would make using ranibizumab risky for me.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the PDS implant and undergo refill-exchanges of ranibizumab 100 mg/mL every 24 weeks

Up to 240 weeks

Visits every 24 weeks, switching to every 12 weeks from Week 144 or 168

Follow-up

Participants are monitored for safety and effectiveness after treatment

72 weeks post-re-implantation

Open-label extension

Participants continue to receive treatment to evaluate long-term safety and tolerability

Long-term

Treatment Details

Interventions

• Ranibizumab

Trial Overview The study tests the long-term safety of a Port Delivery System with ranibizumab (PDS), which is an implant designed to continuously deliver medication for treating nAMD over an extended period without frequent injections.

Participant Groups

Group I: Sub-study 2: 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 with ranibizumab 100 mg/mL Q24W post main study re-implantation visit.

Group II: Sub-study 2: 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 with ranibizumab 100 mg/mL Q24W post main study re-implantation visit.

Group III: Sub-study 2: Cohort 1 Experimental Treatment 1 Intervention

Participants will undergo re-implantation with the updated PDS implant and receive 2 refill-exchanges of ranibizumab 100 mg/mL Q24W.

Group IV: Sub-study 1: PDS Implant Experimental Treatment 1 Intervention

Participants will receive PDS implant using TPC on Day 1 followed by refill-exchanges of ranibizumab 100 mg/mL via the PDS Q24W.

Group V: PDS Implant Cohort 7 (ex-US only) Experimental Treatment 1 Intervention

Participants from Study WR42221 randomized to the Q36W arm, who will continue to be treated with refill-exchanges of ranibizumab 100 mg/mL Q36W. Participants will be in the study for a minimum of 144 weeks and may continue after Week 144 until the PDS has received Health Authority approval (or non-approval) in their respective country and/or until the decision to close the study has been made by the sponsor.

Group VI: PDS Implant Cohort 6 (ex-US only) Experimental Treatment 1 Intervention

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 will be in the study for a minimum of 144 weeks and may continue after Week 144 until the PDS has received Health Authority approval (or non-approval) in their respective country and/or until the decision to close the study has been made by the sponsor.

Group VII: PDS Implant Cohort 5 (ex-US only) Experimental Treatment 1 Intervention

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 will be in the study for a minimum of 144 weeks and may continue after Week 144 until the PDS has received Health Authority approval (or non-approval) in their respective country and/or until the decision to close the study has been made by the sponsor.

Group VIII: PDS Implant Cohort 4 (US only) Experimental Treatment 1 Intervention

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.

Group IX: PDS Implant Cohort 3 (US only) Experimental Treatment 1 Intervention

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.

Group X: PDS Implant Cohort 2 (US only) Experimental Treatment 1 Intervention

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.

Group XI: PDS Implant Cohort 1 (US only) Experimental Treatment 1 Intervention

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.

Ranibizumab is already approved in European Union, United States for the following indications:

Approved in European Union as Lucentis for:

• Neovascular age-related macular degeneration (nAMD)
• Diabetic macular edema (DME)
• Macular edema following retinal vein occlusion (RVO)
• Diabetic retinopathy (DR)
• Myopic choroidal neovascularization (mCNV)

Approved in United States as Lucentis/Susvimo for:

• Neovascular age-related macular degeneration (nAMD)
• Diabetic macular edema (DME)
• Macular edema following retinal vein occlusion (RVO)
• Diabetic retinopathy (DR)
• Myopic choroidal neovascularization (mCNV)

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

After 7 to 8 years of intensive ranibizumab therapy for exudative age-related macular degeneration (AMD), 37% of patients achieved a best-corrected visual acuity (BCVA) of 20/70 or better, indicating that a significant portion of patients maintained good visual outcomes.

Despite some patients showing stability, 34% experienced a decline of 15 letters or more in visual acuity, highlighting that even long-term treatment does not eliminate the risk of substantial visual decline in AMD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Seven-year outcomes in ranibizumab-treated patients in ANCHOR, MARINA, and HORIZON: a multicenter cohort study (SEVEN-UP). Rofagha, S., Bhisitkul, RB., Boyer, DS., et al.[2022]

In a real-world clinical setting, 5-year treatment with ranibizumab for neovascular age-related macular degeneration (nAMD) resulted in half of the patients maintaining stable or improved vision, with 45.5% showing no significant vision loss.

The study involved 44 eyes from 37 patients, revealing that the average number of visits (25.3) and injections (12.6) over 5 years were lower than those reported in controlled clinical trials, suggesting a more manageable treatment regimen in everyday practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year Outcomes of Ranibizumab in Neovascular Age-related Macular Degeneration: Real Life Clinical Experience. Ozkaya, A., Alkin, Z., Togac, M., et al.[2022]

The Port Delivery System (PDS) with ranibizumab is a new long-acting treatment for neovascular age-related macular degeneration (nAMD) that continuously delivers medication for up to 6 months, addressing the issue of undertreatment that leads to vision loss.

In a phase 3 trial, the PDS demonstrated similar improvements in visual acuity compared to monthly injections of ranibizumab, with manageable adverse events, marking it as the first FDA-approved continuous delivery system for anti-VEGF therapy in nAMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of the Port Delivery System with ranibizumab for neovascular age-related macular degeneration. Adamis, AP., de Juan, E.[2023]

The combination therapy of intravitreal ranibizumab and a dexamethasone implant resulted in significantly fewer retreatments over 12 months compared to ranibizumab alone, indicating improved management of neovascular age-related macular degeneration.

Both treatment groups maintained similar visual acuity and macular sensitivity, suggesting that the combination therapy does not compromise functional outcomes while potentially enhancing treatment efficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ROLE OF ADDITIONAL DEXAMETHASONE FOR THE MANAGEMENT OF PERSISTENT OR RECURRENT NEOVASCULAR AGE-RELATED MACULAR DEGENERATION UNDER RANIBIZUMAB TREATMENT. Rezar-Dreindl, S., Eibenberger, K., Buehl, W., et al.[2022]

In a 24-month study involving 454 patients who switched from ranibizumab to aflibercept and 750 who remained on ranibizumab, there was no significant difference in visual acuity change, indicating that switching does not provide additional benefits in terms of vision improvement.

Patients who switched to aflibercept had more treatment visits and injections compared to those who stayed on ranibizumab, suggesting that switching may lead to increased healthcare resource use without enhancing treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Continued Ranibizumab Therapy in Neovascular Age-Related Macular Degeneration versus Switch to Aflibercept: Real World Evidence. Chakravarthy, U., Bezlyak, V., Sagkriotis, A., et al.[2019]

Ranibizumab (Lucentis) effectively targets VEGF-A to treat wet age-related macular degeneration (AMD) by blocking its active isoforms, demonstrating its ability to penetrate retinal layers and reach the affected tissue.

The use of ranibizumab is associated with a low incidence of systemic adverse effects, as studies (MARINA and ANCHOR) showed no significant difference in adverse event frequency between treated patients and controls, indicating its safety for AMD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of ranibizumab therapy in wet AMD and the role of vascular endothelial growth factors in physiological angiogenesis. Figurska, M., Robaszkiewicz, J., Wierzbowska, J.[2015]

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]

In a 5-year study involving 30,138 patients, those with neovascular age-related macular degeneration (nAMD) who were previously treated with ranibizumab maintained their visual acuity at Year 1, with a mean change of -1.6 letters, indicating stability in vision despite ongoing treatment.

Patients receiving more than 6 ranibizumab injections showed a positive trend, gaining an average of 0.5 letters in visual acuity, while the overall safety profile remained consistent with no new safety concerns reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ranibizumab treatment patterns in prior ranibizumab-treated neovascular age-related macular degeneration patients: Real-world outcomes from the LUMINOUS study. Holz, FG., Minnella, AM., Tuli, R., et al.[2021]

In a long-term study involving 853 patients, multiple intravitreal injections of ranibizumab were found to be well tolerated over a period of 4 years, with a very low incidence of serious adverse events, including only one case of mild endophthalmitis.

Patients who received continuous ranibizumab treatment maintained better visual acuity compared to those who had less frequent follow-ups, indicating that consistent treatment is crucial for preserving vision in patients with age-related macular degeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HORIZON: an open-label extension trial of ranibizumab for choroidal neovascularization secondary to age-related macular degeneration. Singer, MA., Awh, CC., Sadda, S., et al.[2022]

In a 24-month study involving 234 patients with neovascular age-related macular degeneration, intravitreal ranibizumab injections were found to be well tolerated, with no new safety concerns identified over three years of treatment.

Despite the treatment, patients experienced an average decline in best-corrected visual acuity (BCVA) by 4.3 letters from baseline, suggesting potential undertreatment or disease progression, as many patients did not receive injections despite significant visual acuity loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The SECURE study: long-term safety of ranibizumab 0.5 mg in neovascular age-related macular degeneration. Silva, R., Axer-Siegel, R., Eldem, B., 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]

In a study involving 220 eyes of patients with neovascular age-related macular degeneration (nAMD), the Port Delivery System (PDS) with ranibizumab did not show worse rates of macular atrophy (MA) compared to monthly intravitreal ranibizumab injections over a mean follow-up of 22.1 months.

Patients treated with the PDS had a lower incidence of developing MA compared to those receiving monthly injections, suggesting that the PDS may be a safer option for maintaining retinal health in nAMD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence and Progression of Macular Atrophy in Eyes with Neovascular Age-Related Macular Degeneration in the Phase 2 Ladder Trial of the Port Delivery System with Ranibizumab. Jaffe, GJ., Cameron, B., Kardatzke, D., et al.[2022]

In a study of 87 patients with neovascular age-related macular degeneration treated with ranibizumab over 12 months, those with poor baseline visual acuity (24-34 ETDRS letters) experienced the greatest improvement in vision, gaining an average of 14 letters.

While patients with better baseline visual acuity (≥55 letters) had a smaller average gain of 2.85 letters, they achieved a better final visual acuity, indicating that initial vision levels influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Visual acuity outcomes in ranibizumab-treated neovascular age-related macular degeneration; stratified by baseline vision. Shona, O., Gupta, B., Vemala, R., et al.[2016]

References

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

Seven-year outcomes in ranibizumab-treated patients in ANCHOR, MARINA, and HORIZON: a multicenter cohort study (SEVEN-UP). [2022]

2. Korea (South) pubmed.ncbi.nlm.nih.gov

Five-year Outcomes of Ranibizumab in Neovascular Age-related Macular Degeneration: Real Life Clinical Experience. [2022]

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

Development of the Port Delivery System with ranibizumab for neovascular age-related macular degeneration. [2023]

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

ROLE OF ADDITIONAL DEXAMETHASONE FOR THE MANAGEMENT OF PERSISTENT OR RECURRENT NEOVASCULAR AGE-RELATED MACULAR DEGENERATION UNDER RANIBIZUMAB TREATMENT. [2022]

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

Effectiveness of Continued Ranibizumab Therapy in Neovascular Age-Related Macular Degeneration versus Switch to Aflibercept: Real World Evidence. [2019]

6. Poland pubmed.ncbi.nlm.nih.gov

Safety of ranibizumab therapy in wet AMD and the role of vascular endothelial growth factors in physiological angiogenesis. [2015]

7. 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]

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

Ranibizumab treatment patterns in prior ranibizumab-treated neovascular age-related macular degeneration patients: Real-world outcomes from the LUMINOUS study. [2021]

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

HORIZON: an open-label extension trial of ranibizumab for choroidal neovascularization secondary to age-related macular degeneration. [2022]

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

The SECURE study: long-term safety of ranibizumab 0.5 mg in neovascular age-related macular degeneration. [2022]

11. 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]

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

Prevalence and Progression of Macular Atrophy in Eyes with Neovascular Age-Related Macular Degeneration in the Phase 2 Ladder Trial of the Port Delivery System with Ranibizumab. [2022]

13. Australia pubmed.ncbi.nlm.nih.gov

Visual acuity outcomes in ranibizumab-treated neovascular age-related macular degeneration; stratified by baseline vision. [2016]