Study of the Efficacy and Safety of the Ranibizumab Port Delivery System (RPDS) for Sustained Delivery of Ranibizumab in Participants With Subfoveal Neovascular Age-Related Macular Degeneration (AMD) (LADDER)
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ClinicalTrials.gov Identifier: NCT02510794 |
Recruitment Status :
Completed
First Posted : July 29, 2015
Last Update Posted : June 10, 2019
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Macular Degeneration | Drug: Ranibizumab | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 238 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | A Phase II, Multicenter, Randomized, Active Treatment-Controlled Study of the Efficacy and Safety of the Ranibizumab Port Delivery System for Sustained Delivery of Ranibizumab in Patients With Subfoveal Neovascular Age-Related Macular Degeneration |
Actual Study Start Date : | September 28, 2015 |
Actual Primary Completion Date : | April 10, 2018 |
Actual Study Completion Date : | March 28, 2019 |

Arm | Intervention/treatment |
---|---|
Experimental: Ranibizumab Dose 1
Participants will receive ranibizumab delivered through the implant with Dose 1 formulation in the study eye on Day 1 and if required, implant refill will be done starting from Month 1 according to protocol-defined refill criteria.
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Drug: Ranibizumab
Ranibizumab will be administered at dose of 0.5 mg monthly ITV injections of 10-mg/mL formulation or delivered through the implant with three different formulations (Dose 1, 2 and 3).
Other Name: Lucentis® |
Experimental: Ranibizumab Dose 2
Participants will receive ranibizumab delivered through the implant with Dose 2 formulation in the study eye on Day 1 and if required, implant refill will be done starting from Month 1 according to protocol-defined refill criteria.
|
Drug: Ranibizumab
Ranibizumab will be administered at dose of 0.5 mg monthly ITV injections of 10-mg/mL formulation or delivered through the implant with three different formulations (Dose 1, 2 and 3).
Other Name: Lucentis® |
Experimental: Ranibizumab Dose 3
Participants will receive ranibizumab delivered through the implant with Dose 3 formulation in the study eye on Day 1 and if required, implant refill will be done starting from Month 1 according to protocol-defined refill criteria.
|
Drug: Ranibizumab
Ranibizumab will be administered at dose of 0.5 mg monthly ITV injections of 10-mg/mL formulation or delivered through the implant with three different formulations (Dose 1, 2 and 3).
Other Name: Lucentis® |
Active Comparator: Ranibizumab 0.5 mg ITV injection
Participants will receive ranibizumab 0.5 mg monthly ITV injections of 10 mg/mL formulation at Day 1 and every month thereafter.
|
Drug: Ranibizumab
Ranibizumab will be administered at dose of 0.5 mg monthly ITV injections of 10-mg/mL formulation or delivered through the implant with three different formulations (Dose 1, 2 and 3).
Other Name: Lucentis® |
- Time Until a Participant First Requires the RPDS Implant Refill According to Protocol-Defined Refill Criteria [ Time Frame: Baseline up to approximately 38 months ]
- Change From Baseline in Best Corrected Visual Acuity (BCVA) at Month 9 [ Time Frame: Baseline, Month 9 ]
- Change From Baseline in BCVA Over Time [ Time Frame: Baseline up to Month 38 ]
- Average Change From Baseline in BCVA Over Time [ Time Frame: Baseline up to Month 38 ]
- Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) [ Time Frame: Baseline up to Month 38 ]
- Number of Implant Clogging at Month 9 [ Time Frame: Month 9 ]
- Observed Maximum Serum concentration (Cmax) of Ranibizumab [ Time Frame: Predose (0 hour) on Day 1 up to approximately 38 months (detailed timeframe is provided in description field) ]ITV: Predose (0 hour) on Day 1 and Months 1,3,6,9, and at study completion (up to approximately 38 months); RPDS: Predose (0 hour) on Day 1, 1 hour post treatment on Day 1, Day 2, Day 7, and Day 14, Predose (0 hour) Monthly and as applicable on Day 1 and 7 post treatment starting at Month 2 (up to approximately 38 months)
- Area Under the Concentration-Time Curve (AUC) of Ranibizumab [ Time Frame: Predose (0 hour) on Day 1 up to approximately 38 months (detailed timeframe is provided in description field) ]ITV: Predose (0 hour) on Day 1 and Months 1,3,6,9, and at study completion (up to approximately 38 months); RPDS: Predose (0 hour) on Day 1, 1 hour post treatment on Day 1, Day 2, Day 7, and Day 14, Predose (0 hour) Monthly and as applicable on Day 1 and 7 post treatment starting at Month 2 (up to approximately 38 months)
- Time to Maximum Concentration (Tmax) of Ranibizumab [ Time Frame: Predose (0 hour) on Day 1 up to approximately 38 months (detailed timeframe is provided in description field) ]ITV: Predose (0 hour) on Day 1 and Months 1,3,6,9, and at study completion (up to approximately 38 months); RPDS: Predose (0 hour) on Day 1, 1 hour post treatment on Day 1, Day 2, Day 7, and Day 14, Predose (0 hour) Monthly and as applicable on Day 1 and 7 post treatment starting at Month 2 (up to approximately 38 months)
- Terminal Half-Life (t1/2) of Ranibizumab [ Time Frame: Predose (0 hour) on Day 1 up to approximately 38 months (detailed timeframe is provided in description field) ]ITV: Predose (0 hour) on Day 1 and Months 1,3,6,9, and at study completion (up to approximately 38 months); RPDS: Predose (0 hour) on Day 1, 1 hour post treatment on Day 1, Day 2, Day 7, and Day 14, Predose (0 hour) Monthly and as applicable on Day 1 and 7 post treatment starting at Month 2 (up to approximately 38 months)
- Observed Serum Concentration (Ct) of Ranibizumab Over Time [ Time Frame: Predose (0 hour) on Day 1 up to approximately 38 months (detailed timeframe is provided in description field) ]ITV: Predose (0 hour) on Day 1 and Months 1,3,6,9, and at study completion (up to approximately 38 months); RPDS: Predose (0 hour) on Day 1, 1 hour post treatment on Day 1, Day 2, Day 7, and Day 14, Predose (0 hour) Monthly and as applicable on Day 1 and 7 post treatment starting at Month 2 (up to approximately 38 months)
- Observed Steady-State Serum Concentration at the end of a Dosing Interval (Ctrough) of Ranibizumab [ Time Frame: Predose (0 hour) on Day 1 up to approximately 38 months (detailed timeframe is provided in description field) ]ITV: Predose (0 hour) on Day 1 and Months 1,3,6,9, and at study completion (up to approximately 38 months); RPDS: Predose (0 hour) on Day 1, 1 hour post treatment on Day 1, Day 2, Day 7, and Day 14, Predose (0 hour) Monthly and as applicable on Day 1 and 7 post treatment starting at Month 2 (up to approximately 38 months)
- Percentage of Participants With Ocular and Non-Ocular Adverse Events (AEs) and Serious AEs (SAEs) [ Time Frame: Baseline up to approximately Month 38 ]
- Percentage of Participants With Positive Serum Antibodies to Ranibizumab [ Time Frame: Baseline, Predose (0 hour) on Day 14, Months 1, 3, 6, 9, and at early termination (up to approximately 38 months) ]

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Ages Eligible for Study: | 50 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Newly diagnosed with wet AMD within 9 months of screening visit
- Participant must have received at least 2 prior ITV anti-vascular endothelial growth factor (VEGF) injections. However, the most recent anti-VEGF injection must have been ranibizumab and must have occurred at least 7 days prior to the screening visit
- Demonstrated response to prior ITV anti-VEGF treatment
- Best Corrected Visual Acuity (BCVA) using Early Treatment Diabetic Retinopathy Study (ETDRS) charts of 20/20-20/200 Snellen equivalent
Exclusion Criteria:
- Treatment with ITV anti-VEGF agents other than ranibizumab within 1 month prior to the randomization visit in either eye
- Study eye treatment with ITV anti-VEGF agents other than ranibizumab within 1 month prior to the randomization visit
- History of laser photocoagulation, Visudyne®, ITV corticosteroid injection, vitrectomy surgery, submacular surgery, device implantation, or other surgical intervention for AMD in the study eye
- Prior participation in a clinical trial involving anti-angiogenic drugs, other than ranibizumab, in either eye within 2 months of the randomization visit
- Subretinal hemorrhage in the study eye that involves the center of the fovea
- Subfoveal fibrosis, or atrophy in the study eye
- Choroidal neovascularization (CNV) in either eye due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia
- Uncontrolled ocular hypertension or glaucoma in the study eye
- History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery in the study eye
- Uncontrolled blood pressure
- Uncontrolled atrial fibrillation within 3 months of informed consent
- History of myocardial infarction or stroke within the last 3 months prior to informed consent
- History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of ranibizumab or placement of the Implant, that might affect interpretation of the results of the study or renders the participant at high risk of treatment complications
- Use of oral corticosteroids
- Current treatment for any active systemic infection
- Use of anticoagulants, anti-platelets (other than aspirin), or medications known to exert similar effects
- Active malignancy within 12 months of randomization
- History of allergy to fluorescein
- Previous participation in any non-ocular (systemic) disease studies of investigational drugs within 1 month preceding the informed consent (excluding vitamins and minerals)

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02510794

Study Director: | Clinical Trials | Hoffmann-La Roche |
Responsible Party: | Genentech, Inc. |
ClinicalTrials.gov Identifier: | NCT02510794 |
Other Study ID Numbers: |
GX28228 |
First Posted: | July 29, 2015 Key Record Dates |
Last Update Posted: | June 10, 2019 |
Last Verified: | June 2019 |
Ranibizumab Macular Degeneration Retinal Degeneration Retinal Diseases Eye Diseases Angiogenesis Inhibitors |
Angiogenesis Modulating Agents Growth Substances Physiological Effects of Drugs Growth Inhibitors Antineoplastic Agents |