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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 : Active, not recruiting
First Posted : July 29, 2015
Last Update Posted : August 8, 2018
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

July 17, 2015
July 29, 2015
August 8, 2018
September 28, 2015
May 30, 2018   (Final data collection date for primary outcome measure)
Time Until a Participant First Requires the RPDS Implant Refill According to Protocol-Defined Refill Criteria [ Time Frame: Baseline up to approximately 38 months ]
Time until a patient first requires the RPDS Implant refill according to protocol-defined refill criteria [ Time Frame: Up to 19 months ]
Complete list of historical versions of study NCT02510794 on ClinicalTrials.gov Archive Site
  • 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) ]
  • Mean Change in BCVA [ Time Frame: From baseline to Month 9 ]
  • Mean Average Change in BCVA [ Time Frame: Up to 19 months ]
  • Mean change from baseline in central foveal thickness over time, as assessed on SD-OCT [ Time Frame: Up to 19 months ]
  • Incidence of ocular and non-ocular AEs and SAEs [ Time Frame: Up to 19 months ]
  • Incidence of AEs of Special Interest [ Time Frame: Up to 19 months ]
Not Provided
Not Provided
 
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)
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
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.
Not Provided
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Macular Degeneration
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 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.
    Intervention: Drug: Ranibizumab
  • 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.
    Intervention: Drug: Ranibizumab
  • 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.
    Intervention: Drug: Ranibizumab
  • 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.
    Intervention: Drug: Ranibizumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
220
Same as current
February 2, 2019
May 30, 2018   (Final data collection date for primary outcome measure)

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)
Sexes Eligible for Study: All
50 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT02510794
GX28228
Not Provided
Not Provided
Not Provided
Genentech, Inc.
Genentech, Inc.
Not Provided
Study Director: Clinical Trials Hoffmann-La Roche
Genentech, Inc.
August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP