Clinical trial NCT02510794: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Macular Degeneration
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2015-07-29
Enrollment: 225
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).


Eligibility 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)

Primary outcomes:
measure: Time Until a Participant First Requires the Implant Refill According to Protocol-Defined Refill Criteria
timeFrame: Baseline up to approximately 38 months
Secondary outcomes:
measure: Change From Baseline in Best Corrected Visual Acuity (BCVA) Averaged At Month 9 and 10
timeFrame: Baseline, Months 9, 10
measure: Change From Baseline in BCVA Over Time
timeFrame: Baseline up to Month 10
measure: Adjusted Average Change From Baseline in BCVA Over Time (MMRM Analysis)
timeFrame: Baseline up to Month 10
measure: Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT)
timeFrame: Baseline up to Month 9
measure: Number of Implant Clogging at Month 9
timeFrame: Month 9
measure: Observed Maximum Serum Concentration (Cmax) of Ranibizumab
timeFrame: Predose (0 hour) on Day 1 up to 38 months
measure: Area Under the Concentration-Time Curve From Dosing to Last Observation (AUClast) of Ranibizumab
timeFrame: Predose (0 hour) on Day 1 up to approximately 38 months (detailed timeframe is provided in description field)
measure: Time to Maximum Concentration (Tmax) of Ranibizumab
timeFrame: Predose (0 hour) on Day 1 up to 38 months
measure: Terminal Half-Life (t1/2) of Ranibizumab
timeFrame: Predose (0 hour) on Day 1 up to 38 months
measure: Observed Steady-State Serum Concentration at the End of a Dosing Interval (Ctrough) of Ranibizumab
timeFrame: Predose (0 hour) on Day 1 up to 38 months
measure: Number of Participants With Ocular and Non-Ocular Adverse Events (AEs) and Serious AEs (SAEs)
timeFrame: Baseline up to approximately Month 38
measure: Percentage of Participants With Positive Serum Antibodies to Ranibizumab
timeFrame: Baseline up to 38 months
Other outcomes:
Locations:
city: Mesa
country: United States
facility: Barnet Dulaney Perkins Eye Center
state: Arizona
city: Phoenix
country: United States
facility: Retinal Research Institute, LLC
state: Arizona
city: Phoenix
country: United States
facility: Associated Retina Consultants
state: Arizona
city: Encino
country: United States
facility: The Retina Partners
state: California
city: La Jolla
country: United States
facility: Jacobs Retina center at the Shiley eye Institute UCSD
state: California
city: Los Angeles
country: United States
facility: Jules Stein Eye Institute/ UCLA
state: California
city: Mountain View
country: United States
facility: N CA Retina Vitreous Assoc
state: California
city: Sacramento
country: United States
facility: Retinal Consultants Med Group
state: California
city: San Francisco
country: United States
facility: West Coast Retina Medical Group
state: California
city: San Francisco
country: United States
facility: UCSF; Ophthalmology
state: California
city: Santa Ana
country: United States
facility: Orange County Retina Med Group
state: California
city: Santa Barbara
country: United States
facility: California Retina Consultants
state: California
city: Colorado Springs
country: United States
facility: Retina Consultants of Southern
state: Colorado
city: Lakewood
country: United States
facility: Colorado Retina Associates, PC
state: Colorado
city: Boynton Beach
country: United States
facility: Florida Eye Microsurgical Inst
state: Florida
city: Fort Myers
country: United States
facility: National Ophthalmic Research Institute
state: Florida
city: Pensacola
country: United States
facility: Retina Specialty Institute
state: Florida
city: Saint Petersburg
country: United States
facility: Retina Vitreous Assoc of FL
state: Florida
city: Tampa
country: United States
facility: Retina Associates of Florida, LLC
state: Florida
city: Augusta
country: United States
facility: Southeast Retina Center
state: Georgia
city: Joliet
country: United States
facility: Illinois Retina Associates
state: Illinois
city: West Des Moines
country: United States
facility: Wolfe Eye Clinic
state: Iowa
city: Lexington
country: United States
facility: Retina Associates of Kentucky
state: Kentucky
city: Paducah
country: United States
facility: Paducah Retinal Center
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Med; Wilmer Eye Inst
state: Maryland
city: Chevy Chase
country: United States
facility: Retina Group of Washington
state: Maryland
city: Towson
country: United States
facility: Retina Specialists
state: Maryland
city: Worcester
country: United States
facility: Vitreo-Retinal Associates, PC
state: Massachusetts
city: Grand Rapids
country: United States
facility: Foundation for Vision Research
state: Michigan
city: Edina
country: United States
facility: Vitreoretinal Surgery
state: Minnesota
city: Reno
country: United States
facility: Sierra Eye Associates
state: Nevada
city: Bloomfield
country: United States
facility: Retina Center of New Jersey
state: New Jersey
city: Cherry Hill
country: United States
facility: Mid Atlantic Retina - Wills Eye Hospital
state: New Jersey
city: Albuquerque
country: United States
facility: Eye Associates of New Mexico
state: New Mexico
city: Albuquerque
country: United States
facility: University of New Mexico; School of Med
state: New Mexico
city: Rochester
country: United States
facility: Retina Assoc of Western NY
state: New York
city: Charlotte
country: United States
facility: Char Eye Ear &Throat Assoc
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Eye Institute
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Portland
country: United States
facility: Retina Northwest
state: Oregon
city: Portland
country: United States
facility: Oregon HSU; Casey Eye Institute
state: Oregon
city: Florence
country: United States
facility: Palmetto Retina Center
state: South Carolina
city: Germantown
country: United States
facility: Charles Retina Institute
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Retina PC.
state: Tennessee
city: Arlington
country: United States
facility: Texas Retina Associates
state: Texas
city: Austin
country: United States
facility: Retina Research Center
state: Texas
city: Bellaire
country: United States
facility: Retina Consultants of Texas
state: Texas
city: San Antonio
country: United States
facility: Med Center Ophthalmology Assoc
state: Texas
city: Salt Lake City
country: United States
facility: Retina Associates of Utah
state: Utah
city: Norfolk
country: United States
facility: Wagner Macula & Retina Center
state: Virginia
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Wykoff CC, Campochiaro PA, Pieramici DJ, Khanani AM, Gune S, Maia M, Kagedal M, Ding HT, Maass KF. Pharmacokinetics of the Port Delivery System with Ranibizumab in the Ladder Phase 2 Trial for Neovascular Age-Related Macular Degeneration. Ophthalmol Ther. 2022 Oct;11(5):1705-1717. doi: 10.1007/s40123-022-00532-9. Epub 2022 Jun 27.
citation: Yohe S, Maass KF, Horvath J, Rea J, Barteselli G, Ranade SV. In-vitro characterization of ranibizumab release from the Port Delivery System. J Control Release. 2022 May;345:101-107. doi: 10.1016/j.jconrel.2022.03.005. Epub 2022 Mar 4.