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) - Full Text View

Purpose

This is a Phase II clinical study to evaluate the efficacy, safety and pharmacokinetics of three different formulations of ranibizumab delivered via RPDS implant compared with the standard of care (SOC) intravitreal (ITV) injections of ranibizumab, in participants with subfoveal neovascular AMD.

Condition	Intervention	Phase
Macular Degeneration	Drug: Ranibizumab	Phase 2


Study Type:	Interventional
Study Design:	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

Resource links provided by NLM:

Genetics Home Reference related topics: age-related macular degeneration

MedlinePlus related topics: Macular Degeneration

Drug Information available for: Ranibizumab

U.S. FDA Resources

Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:

Time Until a Participant First Requires the RPDS Implant Refill According to Protocol-Defined Refill Criteria [ Time Frame: Baseline up to approximately 38 months ]

Secondary Outcome Measures:

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) ]


Estimated Enrollment:	220
Actual Study Start Date:	September 28, 2015
Estimated Study Completion Date:	March 31, 2019
Estimated Primary Completion Date:	September 30, 2018 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.	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®

Eligibility


Ages Eligible for Study:	50 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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)

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02510794

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Sponsors and Collaborators

Genentech, Inc.

Investigators


Study Director:	Clinical Trials	Hoffmann-La Roche

More Information


Responsible Party:	Genentech, Inc.
ClinicalTrials.gov Identifier:	NCT02510794 History of Changes
Other Study ID Numbers:	GX28228
Study First Received:	July 17, 2015
Last Updated:	September 15, 2017

Additional relevant MeSH terms:


Ranibizumab Macular Degeneration Wet Macular Degeneration Retinal Degeneration Retinal Diseases Eye Diseases Immunologic Factors	Physiological Effects of Drugs Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Growth Inhibitors Antineoplastic Agents

ClinicalTrials.gov processed this record on September 19, 2017