A Phase III Study to Evaluate the Port Delivery System With Ranibizumab Compared With Monthly Ranibizumab Injections in Participants With Wet Age-Related Macular Degeneration
- Conditions
- Neovascular Age-Related Macular Degeneration
- Interventions
- Drug: PDS Implant filled with 100 mg/mL RanibizumabDrug: Intravitreal Injections of 10 mg/mL Ranibizumab
- Registration Number
- NCT03677934
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
Study GR40548 is a Phase III, randomized, multicenter, open-label (visual assessor \[VA\]-masked), active-comparator study designed to assess the efficacy, safety, and pharmacokinetics (PK) of 100mg/ml delivered via the Port Delivery System with ranibizumab (PDS) compared with ranibizumab intravitreal injections at 0.5 mg (10 mg/mL) in participants with neovascular age-related macular degeneration (nAMD).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 415
- Age ≥50 years, at time of signing Informed Consent Form
- Initial diagnosis of exudative neovascular age-related macular degeneration (nAMD) within 9 months prior to the screening visit
- Previous treatment with at least three anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections for nAMD per standard of care within 6 months prior to the screening visit
- Demonstrated response to prior anti-VEGF intravitreal treatment since diagnosis
- Best-corrected visual acuity (BCVA) of 34 letters or better
- Subfoveal fibrosis or subfoveal atrophy in study eye
- Subretinal hemorrhage that involves the center of the fovea in study eye
- History of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD in study eye
- Prior treatment with Visudyne®, external-beam radiation therapy, or transpupillary thermotherapy in study eye
- Previous intraocular device implantation in study eye
- Previous laser (any type) used for AMD treatment in study eye
- Treatment with anti-VEGF agents other than ranibizumab within 1 month prior to the randomization visit in either eye
- Prior participation in a clinical trial involving anti-VEGF drugs within 6 months prior to the randomization visit, other than ranibizumab in either eye
- CNV due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia in either eye
- Uncontrolled blood pressure
- History of stroke within the last 3 months prior to informed consent
- Uncontrolled atrial fibrillation within 3 months of informed consent
- History of myocardial infarction within the last 3 months prior to informed consent
- History of other disease, metabolic dysfunction, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of ranibizumab or placement of the Implant and that might affect interpretation of the results of the study or renders the participant at high risk of treatment complications in the opinion of the investigator
- Current systemic treatment for a confirmed active systemic infection
- Chronic use of oral corticosteroids
- Active cancer within 12 months of randomization
- Previous participation in any non-ocular (systemic) disease studies of investigational drugs within 1 month preceding the informed consent (excluding vitamins and minerals)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PDS Implant Arm PDS Implant filled with 100 mg/mL Ranibizumab Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals Intravitreal Arm Intravitreal Injections of 10 mg/mL Ranibizumab Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
- Primary Outcome Measures
Name Time Method Change From Baseline in Best-Corrected Visual Acuity (BCVA) Score at the Average of Week 36 and Week 40, as Assessed Using the ETDRS Visual Acuity Chart at a Starting Distance of 4 Meters Baseline, and the average of Week 36 and Week 40 The primary efficacy endpoint is the change in BCVA score from baseline averaged over Weeks 36 and 40 with BCVA assessed using the ETDRS chart at a starting distance of 4 meters. ETDRS = Early Treatment Diabetic Retinopathy Study.
The primary objective is to determine the NI and equivalence between the two treatment groups, as measured by the primary efficacy endpoint with a NI margin of 4.5 letters and equivalence margins of ± 4.5 letters.
A vision score of 20/20 vision is considered normal. A score of 20/200 is considered being legally blind.
- Secondary Outcome Measures
Name Time Method Change From Baseline in BCVA Score Averaged Over Week 60 and Week 64 Baseline, Week60, Week 64 Change From Baseline in BCVA Score Over Time Baseline up to Week 96 Percentage of Participants Who Lose <10 or <5 Letters in BCVA Score From Baseline to the Average Over Week 36 and Week 40 Baseline, and the average of Week 36 and Week 40 Percentage of Participants Who Gain ≥0 Letters in BCVA Score From Baseline Over Time Baseline up to Week 96 Change From Baseline in CPT Over Time Baseline up to Week 96 Percentage of Participants With Ocular and Systemic (Non-Ocular) AEs Randomization to Week 96 Percentage of Participants With Adverse Events of Special Interest Randomization to Week 96 Percentage of Participants with Adverse Events of Special Interest
Observed Serum Ranibizumab Concentrations at Specified Timepoints Randomization to Week 96 Percentage of Participants in the PDS Implant Arm Who Undergo Supplemental Treatment With Intravitreal Ranibizumab 0.5 mg Before the First, Second, Third, and Fourth Fixed Refill-Exchange Intervals Day 1 to Week 24, Week 25 to Week 48, Week 49 to Week 72, Week73 to Week 96 Percentage of Participants With BCVA Score of 38 Letters (20/200 Approximate Snellen Equivalent) or Worse Over Time Baseline up to Week 96 Percentage of Participants With BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better at the Average Over Week 36 and Week 40 Baseline, and the average of Week 36 and Week 40 Percentage of Participants With BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better Over Time Baseline up to Week 96 Percentage of Participants Who Gain ≥0 Letters in BCVA Score From Baseline to the Average Over Week 36 and Week 40 Baseline up to Week 40 Percentage of Participants in the PDS Implant Arm Who Undergo a Supplemental Treatment That Requires Subsequent Additional Supplemental Treatments During the Study Week 16 to Week 92 Estimated PK Parameter Values AUC0-6M Randomization to Week 96 AUC0-6M = Area Under the Concentration-Time Curve From 0 to 6 Months
Estimated PK Parameter Value t1/2 After PDS Implant Insertion Randomization to Week 96 Apparent terminal half-life
Estimated PK Parameter Value Cmin Randomization to Week 96 Cmin = Minimum Serum Concentration
Estimated PK Parameter Value Cmax Randomization to Week 96 Cmax = Maximum Serum Concentration
Percentage of Participants Who Lose <10 or <5 Letters in BCVA Score From Baseline Over Time Baseline up to Week 96 Baseline Prevalence and Incidence of Treatment-Emergent ADA Randomization to Week 96 Percentage of Participants With BCVA Score of 38 Letters (20/200 Approximate Snellen Equivalent) or Worse at the Average Over Week 36 and Week 40 Baseline, and the average of Week 36 and Week 40 Change From Baseline in Center Point Thickness (CPT) at Week 36 Baseline to Week 36
Trial Locations
- Locations (75)
Retina Specialists
🇺🇸Towson, Maryland, United States
N CA Retina Vitreous Assoc
🇺🇸Mountain View, California, United States
Sierra Eye Associates
🇺🇸Reno, Nevada, United States
Long Is. Vitreoretinal Consult
🇺🇸Great Neck, New York, United States
Georgia Retina PC
🇺🇸Marietta, Georgia, United States
Retinal Consultants of Arizona
🇺🇸Phoenix, Arizona, United States
Retinal Consultants Med Group
🇺🇸Sacramento, California, United States
Barnet Dulaney Perkins Eye Center
🇺🇸Mesa, Arizona, United States
Jules Stein Eye Institute/ UCLA
🇺🇸Los Angeles, California, United States
Southwest Retina Consultants
🇺🇸Durango, Colorado, United States
The Retina Care Center
🇺🇸Baltimore, Maryland, United States
Retina Vitreous Assoc of FL
🇺🇸Saint Petersburg, Florida, United States
Orange County Retina Med Group
🇺🇸Santa Ana, California, United States
Retina-Vitreous Associates Medical Group
🇺🇸Beverly Hills, California, United States
Eye Center of Northern CO
🇺🇸Fort Collins, Colorado, United States
Retina Specialty Institute
🇺🇸Pensacola, Florida, United States
UCSF; Ophthalmology
🇺🇸San Francisco, California, United States
The Retina Partners
🇺🇸Encino, California, United States
Retina Consultants, San Diego
🇺🇸Poway, California, United States
Tennessee Retina PC
🇺🇸Nashville, Tennessee, United States
Maine Eye Center
🇺🇸Portland, Maine, United States
Colorado Retina Associates, PC
🇺🇸Lakewood, Colorado, United States
Char Eye Ear &Throat Assoc
🇺🇸Charlotte, North Carolina, United States
Foundation for Vision Research
🇺🇸Grand Rapids, Michigan, United States
Texas Retina Associates
🇺🇸Fort Worth, Texas, United States
NJ Retina Teaneck Clinic
🇺🇸Toms River, New Jersey, United States
Retina Northwest
🇺🇸Portland, Oregon, United States
Retina Vitreous Center
🇺🇸Edmond, Oklahoma, United States
Ophthalmic Consultants of Long Island
🇺🇸Rockville Centre, New York, United States
OSU Eye Physicians & Surgeons
🇺🇸Columbus, Ohio, United States
Retina Center Northwest
🇺🇸Silverdale, Washington, United States
Spokane Eye Clinical Research
🇺🇸Spokane, Washington, United States
Austin Clinical Research LLC
🇺🇸Austin, Texas, United States
Charles Retina Institute
🇺🇸Memphis, Tennessee, United States
Retina Associates of Utah
🇺🇸Salt Lake City, Utah, United States
Rocky Mountain Retina
🇺🇸Salt Lake City, Utah, United States
Retina Institute of Virginia
🇺🇸Richmond, Virginia, United States
Palmetto Retina Center
🇺🇸Florence, South Carolina, United States
Ophthalmic Consultants of Boston
🇺🇸Boston, Massachusetts, United States
Cincinnati Eye Institute
🇺🇸Cincinnati, Ohio, United States
Associated Retina Consultants
🇺🇸Phoenix, Arizona, United States
Arizona Retina and Vitreous Consultants
🇺🇸Phoenix, Arizona, United States
California Retina Consultants
🇺🇸Santa Barbara, California, United States
West Coast Retina Medical Group
🇺🇸San Francisco, California, United States
Retina Care Specialists
🇺🇸Palm Beach Gardens, Florida, United States
Florida Eye Associates
🇺🇸Melbourne, Florida, United States
Retina Group of New England
🇺🇸Waterford, Connecticut, United States
Fort Lauderdale Eye Institute
🇺🇸Plantation, Florida, United States
Southeast Retina Center
🇺🇸Augusta, Georgia, United States
Retina Associates
🇺🇸Lenexa, Kansas, United States
Retina Associates of Kentucky
🇺🇸Lexington, Kentucky, United States
Paducah Retinal Center
🇺🇸Paducah, Kentucky, United States
Johns Hopkins Med; Wilmer Eye Inst
🇺🇸Baltimore, Maryland, United States
Retina Group of Washington
🇺🇸Chevy Chase, Maryland, United States
Vitreous-Retina-Macula
🇺🇸New York, New York, United States
The Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Med Center Ophthalmology Assoc
🇺🇸San Antonio, Texas, United States
Retina Consultants of Texas
🇺🇸Bellaire, Texas, United States
Bay Area Retina Associates
🇺🇸Walnut Creek, California, United States
Wolfe Eye Clinic
🇺🇸West Des Moines, Iowa, United States
VitreoRetinal Surgery, PLLC.; DBA Retina Consultants of Minnesota
🇺🇸Edina, Minnesota, United States
Retina Associates of Florida, LLC
🇺🇸Tampa, Florida, United States
National Ophthalmic Research Institute
🇺🇸Fort Myers, Florida, United States
The Retina Institute - Chesterfield
🇺🇸Chesterfield, Missouri, United States
University Retina and Macula Associates, PC
🇺🇸Lemont, Illinois, United States
Southern Vitreoretinal Assoc
🇺🇸Tallahassee, Florida, United States
Associated Retinal Consultants
🇺🇸Grand Rapids, Michigan, United States
Vitreo-Retinal Associates, PC
🇺🇸Worcester, Massachusetts, United States
Austin Retina Associates
🇺🇸Austin, Texas, United States
Midwest Vision Research Foundation
🇺🇸Chesterfield, Missouri, United States
Mid Atlantic Retina - Wills Eye Hospital
🇺🇸Cherry Hill, New Jersey, United States
Envision Ocular, LLC
🇺🇸Bloomfield, New Jersey, United States
Retina Vit Surgeons/Central NY
🇺🇸Liverpool, New York, United States
Wagner Macula & Retina Center
🇺🇸Norfolk, Virginia, United States
Illinois Retina Associates
🇺🇸Joliet, Illinois, United States