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

Macular Degeneration Clinical Trial

— LADDER  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02510794
• Other study ID #: GX28228
• Status: Completed
• Phase: Phase 2
• Start date: September 28, 2015
• Est. completion date: March 28, 2019

Study information

• Verified date: April 2021
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase II multicenter, dose-ranging, randomized, active treatment (monthly ITV injection)-controlled study to evaluate the efficacy, safety, and pharmacokinetics of ranibizumab delivered through the Implant using three ranibizumab formulation arms (10 mg/mL, 40 mg/mL, and 100 mg/mL) compared with the control arm (0.5-mg monthly ITV injections of 10-mg/mL formulation) in participants with subfoveal neovascular age-related macular degeneration (nAMD).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 225
• Est. completion date: March 28, 2019
• Est. primary completion date: April 10, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Macular Degeneration

Intervention

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.

Locations

Country	Name	City	State
United States	Eye Associates of New Mexico	Albuquerque	New Mexico
United States	University of New Mexico; School of Med	Albuquerque	New Mexico
United States	Texas Retina Associates	Arlington	Texas
United States	Southeast Retina Center	Augusta	Georgia
United States	Retina Research Center	Austin	Texas
United States	Johns Hopkins Med; Wilmer Eye Inst	Baltimore	Maryland
United States	Retina Consultants of Texas	Bellaire	Texas
United States	Retina Center of New Jersey	Bloomfield	New Jersey
United States	Florida Eye Microsurgical Inst	Boynton Beach	Florida
United States	Char Eye Ear &Throat Assoc	Charlotte	North Carolina
United States	Mid Atlantic Retina - Wills Eye Hospital	Cherry Hill	New Jersey
United States	Retina Group of Washington	Chevy Chase	Maryland
United States	Cincinnati Eye Institute	Cincinnati	Ohio
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	Retina Consultants of Southern	Colorado Springs	Colorado
United States	Vitreoretinal Surgery	Edina	Minnesota
United States	The Retina Partners	Encino	California
United States	Palmetto Retina Center	Florence	South Carolina
United States	National Ophthalmic Research Institute	Fort Myers	Florida
United States	Charles Retina Institute	Germantown	Tennessee
United States	Foundation for Vision Research	Grand Rapids	Michigan
United States	Illinois Retina Associates	Joliet	Illinois
United States	Jacobs Retina center at the Shiley eye Institute UCSD	La Jolla	California
United States	Colorado Retina Associates, PC	Lakewood	Colorado
United States	Retina Associates of Kentucky	Lexington	Kentucky
United States	Jules Stein Eye Institute/ UCLA	Los Angeles	California
United States	Barnet Dulaney Perkins Eye Center	Mesa	Arizona
United States	N CA Retina Vitreous Assoc	Mountain View	California
United States	Tennessee Retina PC.	Nashville	Tennessee
United States	Wagner Macula & Retina Center	Norfolk	Virginia
United States	Paducah Retinal Center	Paducah	Kentucky
United States	Retina Specialty Institute	Pensacola	Florida
United States	Associated Retina Consultants	Phoenix	Arizona
United States	Retinal Research Institute, LLC	Phoenix	Arizona
United States	Oregon HSU; Casey Eye Institute	Portland	Oregon
United States	Retina Northwest	Portland	Oregon
United States	Sierra Eye Associates	Reno	Nevada
United States	Retina Assoc of Western NY	Rochester	New York
United States	Retinal Consultants Med Group	Sacramento	California
United States	Retina Vitreous Assoc of FL	Saint Petersburg	Florida
United States	Retina Associates of Utah	Salt Lake City	Utah
United States	Med Center Ophthalmology Assoc	San Antonio	Texas
United States	UCSF; Ophthalmology	San Francisco	California
United States	West Coast Retina Medical Group	San Francisco	California
United States	Orange County Retina Med Group	Santa Ana	California
United States	California Retina Consultants	Santa Barbara	California
United States	Retina Associates of Florida, LLC	Tampa	Florida
United States	Retina Specialists	Towson	Maryland
United States	Wolfe Eye Clinic	West Des Moines	Iowa
United States	Vitreo-Retinal Associates, PC	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time Until a Participant First Requires the Implant Refill According to Protocol-Defined Refill Criteria	Protocol-Defined Refill Criteria; At 1 month after initial fill: Decrease of = 10 letters in BCVA at the current visit compared with the baseline BCVA, due to nAMD disease activity OR; Increase in CFT of = 100 um at the current visit compared with the baseline CFT, due to nAMD disease activity OR; Presence of new macular hemorrhage, due to nAMD disease activity; For subsequent assessments: Increase in CFT of = 75 µm on SD-OCT at the current visit compared with the average CFT over the last 2 available measurements, due to nAMD disease activity OR; Increase in CFT of = 100 um from the lowest CFT measurement on study, due to nAMD disease activity OR; Decrease of = 5 letters in BCVA at the current visit compared with the average BCVA over the last 2 available measurements, due to nAMD disease activity OR; Decrease of = 10 letters from best recorded BCVA on study, due to nAMD disease activity OR; Presence of new macular hemorrhage, due to nAMD disease activity	Baseline up to approximately 38 months
Secondary	Change From Baseline in Best Corrected Visual Acuity (BCVA) Averaged At Month 9 and 10	Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. The minimum score possible is 0 and maximum possible is 100. A higher score represents better functioning.	Baseline, Months 9, 10
Secondary	Change From Baseline in BCVA Over Time	Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. The minimum score possible is 0 and maximum possible is 100. A higher score represents better functioning.	Baseline up to Month 10
Secondary	Adjusted Average Change From Baseline in BCVA Over Time (MMRM Analysis)	Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. The minimum score possible is 0 and maximum possible is 100. A higher score represents better functioning. Here, the adjusted mean from MMRM analysis is presented).	Baseline up to Month 10
Secondary	Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT)	Central foveal thickness (CFT) is defined as the retinal thickness in the center of the fovea	Baseline up to Month 9
Secondary	Number of Implant Clogging at Month 9	Removed implants identified as meeting serum PK criteria for possible clogging were assessed via lab-based investigation (in vitro drug release testing) to determine whether there was any implant clogging.	Month 9
Secondary	Observed Maximum Serum Concentration (Cmax) of Ranibizumab	The serum pharmacokinetics of ranibizumab were characterized by estimating Cmax between dose intervals. Estimates for these parameters were tabulated and summarized by descriptive statistics.	Predose (0 hour) on Day 1 up to 38 months
Secondary	Area Under the Concentration-Time Curve From Dosing to Last Observation (AUClast) of Ranibizumab	AUCLast is defined as area under the concentration-time curve from dosing (implant or refill) to last observation before next refill or exiting the study. The serum pharmacokinetics of ranibizumab were characterized by estimating AUC between dose intervals. Estimates for these parameters were tabulated and summarized by descriptive statistics.	Predose (0 hour) on Day 1 up to approximately 38 months (detailed timeframe is provided in description field)
Secondary	Time to Maximum Concentration (Tmax) of Ranibizumab	The serum pharmacokinetics of ranibizumab were characterized by estimating Tmax between dose intervals. Estimates for these parameters were tabulated and summarized by descriptive statistics.	Predose (0 hour) on Day 1 up to 38 months
Secondary	Terminal Half-Life (t1/2) of Ranibizumab	The serum pharmacokinetics of ranibizumab were characterized by estimating t1/2 between dose intervals. Estimates for these parameters were tabulated and summarized by descriptive statistics.	Predose (0 hour) on Day 1 up to 38 months
Secondary	Observed Steady-State Serum Concentration at the End of a Dosing Interval (Ctrough) of Ranibizumab		Predose (0 hour) on Day 1 up to 38 months
Secondary	Number of Participants With Ocular and Non-Ocular Adverse Events (AEs) and Serious AEs (SAEs)		Baseline up to approximately Month 38
Secondary	Percentage of Participants With Positive Serum Antibodies to Ranibizumab		Baseline up to 38 months