Clinical trial NCT03677934: 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
Official title: Phase III, Multicenter, Randomized, Visual Assessor-Masked, Active-Comparator Study of the Efficacy, Safety, and Pharmacokinetics of the Port Delivery System With Ranibizumab in Patients With Neovascular Age-Related Macular Degeneration
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Neovascular Age-Related Macular Degeneration
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2018-09-19
Enrollment: 415
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: 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).


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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)

Primary outcomes:
measure: 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
timeFrame: Baseline, and the average of Week 36 and Week 40
Secondary outcomes:
measure: Change From Baseline in BCVA Score Averaged Over Week 60 and Week 64
timeFrame: Baseline, Week60, Week 64
measure: Change From Baseline in BCVA Score Over Time
timeFrame: Baseline up to Week 96
measure: 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
timeFrame: Baseline, and the average of Week 36 and Week 40
measure: Percentage of Participants With BCVA Score of 38 Letters (20/200 Approximate Snellen Equivalent) or Worse Over Time
timeFrame: Baseline up to Week 96
measure: 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
timeFrame: Baseline, and the average of Week 36 and Week 40
measure: Percentage of Participants With BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better Over Time
timeFrame: Baseline up to Week 96
measure: Percentage of Participants Who Lose <10 or <5 Letters in BCVA Score From Baseline to the Average Over Week 36 and Week 40
timeFrame: Baseline, and the average of Week 36 and Week 40
measure: Percentage of Participants Who Lose <10 or <5 Letters in BCVA Score From Baseline Over Time
timeFrame: Baseline up to Week 96
measure: Percentage of Participants Who Gain ≥0 Letters in BCVA Score From Baseline to the Average Over Week 36 and Week 40
timeFrame: Baseline up to Week 40
measure: Percentage of Participants Who Gain ≥0 Letters in BCVA Score From Baseline Over Time
timeFrame: Baseline up to Week 96
measure: Change From Baseline in Center Point Thickness (CPT) at Week 36
timeFrame: Baseline to Week 36
measure: Change From Baseline in CPT Over Time
timeFrame: Baseline up to Week 96
measure: 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
timeFrame: Day 1 to Week 24, Week 25 to Week 48, Week 49 to Week 72, Week73 to Week 96
measure: Percentage of Participants in the PDS Implant Arm Who Undergo a Supplemental Treatment That Requires Subsequent Additional Supplemental Treatments During the Study
timeFrame: Week 16 to Week 92
measure: Percentage of Participants With Ocular and Systemic (Non-Ocular) AEs
timeFrame: Randomization to Week 96
measure: Percentage of Participants With Adverse Events of Special Interest
timeFrame: Randomization to Week 96
measure: Observed Serum Ranibizumab Concentrations at Specified Timepoints
timeFrame: Randomization to Week 96
measure: Estimated PK Parameter Values AUC0-6M
timeFrame: Randomization to Week 96
measure: Estimated PK Parameter Value t1/2 After PDS Implant Insertion
timeFrame: Randomization to Week 96
measure: Estimated PK Parameter Value Cmin
timeFrame: Randomization to Week 96
measure: Estimated PK Parameter Value Cmax
timeFrame: Randomization to Week 96
measure: Baseline Prevalence and Incidence of Treatment-Emergent ADA
timeFrame: Randomization to Week 96
Other outcomes:
Locations:
city: Mesa
country: United States
facility: Barnet Dulaney Perkins Eye Center
state: Arizona
city: Phoenix
country: United States
facility: Associated Retina Consultants
state: Arizona
city: Phoenix
country: United States
facility: Arizona Retina and Vitreous Consultants
state: Arizona
city: Phoenix
country: United States
facility: Retinal Consultants of Arizona
state: Arizona
city: Bakersfield
country: United States
facility: California Retina Consultants
state: California
city: Beverly Hills
country: United States
facility: Retina-Vitreous Associates Medical Group
state: California
city: Encino
country: United States
facility: The Retina Partners
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: Poway
country: United States
facility: Retina Consultants, San Diego
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: Walnut Creek
country: United States
facility: Bay Area Retina Associates
state: California
city: Durango
country: United States
facility: Southwest Retina Consultants
state: Colorado
city: Fort Collins
country: United States
facility: Eye Center of Northern CO
state: Colorado
city: Lakewood
country: United States
facility: Colorado Retina Associates, PC
state: Colorado
city: Waterford
country: United States
facility: Retina Group of New England
state: Connecticut
city: Fort Myers
country: United States
facility: National Ophthalmic Research Institute
state: Florida
city: Melbourne
country: United States
facility: Florida Eye Associates
state: Florida
city: Palm Beach Gardens
country: United States
facility: Retina Care Specialists
state: Florida
city: Pensacola
country: United States
facility: Retina Specialty Institute
state: Florida
city: Plantation
country: United States
facility: Fort Lauderdale Eye Institute
state: Florida
city: Saint Petersburg
country: United States
facility: Retina Vitreous Assoc of FL
state: Florida
city: Tallahassee
country: United States
facility: Southern Vitreoretinal Assoc
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: Marietta
country: United States
facility: Georgia Retina PC
state: Georgia
city: Joliet
country: United States
facility: Illinois Retina Associates
state: Illinois
city: Lemont
country: United States
facility: University Retina and Macula Associates, PC
state: Illinois
city: West Des Moines
country: United States
facility: Wolfe Eye Clinic
state: Iowa
city: Lenexa
country: United States
facility: Retina Associates
state: Kansas
city: Lexington
country: United States
facility: Retina Associates of Kentucky
state: Kentucky
city: Paducah
country: United States
facility: Paducah Retinal Center
state: Kentucky
city: Portland
country: United States
facility: Maine Eye Center
state: Maine
city: Baltimore
country: United States
facility: The Retina Care Center
state: Maryland
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: Boston
country: United States
facility: Ophthalmic Consultants of Boston
state: Massachusetts
city: Worcester
country: United States
facility: Vitreo-Retinal Associates, PC
state: Massachusetts
city: Grand Rapids
country: United States
facility: Associated Retinal Consultants
state: Michigan
city: Grand Rapids
country: United States
facility: Foundation for Vision Research
state: Michigan
city: Edina
country: United States
facility: VitreoRetinal Surgery, PLLC.; DBA Retina Consultants of Minnesota
state: Minnesota
city: Chesterfield
country: United States
facility: Midwest Vision Research Foundation
state: Missouri
city: Chesterfield
country: United States
facility: The Retina Institute - Chesterfield
state: Missouri
city: Reno
country: United States
facility: Sierra Eye Associates
state: Nevada
city: Bloomfield
country: United States
facility: Envision Ocular, LLC
state: New Jersey
city: Cherry Hill
country: United States
facility: Mid Atlantic Retina - Wills Eye Hospital
state: New Jersey
city: Toms River
country: United States
facility: NJ Retina Teaneck Clinic
state: New Jersey
city: Great Neck
country: United States
facility: Long Is. Vitreoretinal Consult
state: New York
city: Liverpool
country: United States
facility: Retina Vit Surgeons/Central NY
state: New York
city: New York
country: United States
facility: Vitreous-Retina-Macula
state: New York
city: Rockville Centre
country: United States
facility: Ophthalmic Consultants of Long Island
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: Columbus
country: United States
facility: OSU Eye Physicians & Surgeons
state: Ohio
city: Edmond
country: United States
facility: Retina Vitreous Center
state: Oklahoma
city: Portland
country: United States
facility: Retina Northwest
state: Oregon
city: Florence
country: United States
facility: Palmetto Retina Center
state: South Carolina
city: Memphis
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: Austin Retina Associates
state: Texas
city: Austin
country: United States
facility: Austin Clinical Research LLC
state: Texas
city: Bellaire
country: United States
facility: Retina Consultants of Texas
state: Texas
city: Fort Worth
country: United States
facility: Texas Retina Associates
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: Salt Lake City
country: United States
facility: Rocky Mountain Retina
state: Utah
city: Norfolk
country: United States
facility: Wagner Macula & Retina Center
state: Virginia
city: Richmond
country: United States
facility: Retina Institute of Virginia
state: Virginia
city: Silverdale
country: United States
facility: Retina Center Northwest
state: Washington
city: Spokane
country: United States
facility: Spokane Eye Clinical Research
state: Washington
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Chang MA, Kapre A, Kaufman D, Kardatzke DR, Rabena M, Patel S, Bobbala A, Gune S, Fung A, Wallenstein G. Patient Preference and Treatment Satisfaction With a Port Delivery System for Ranibizumab vs Intravitreal Injections in Patients With Neovascular Age-Related Macular Degeneration: A Randomized Clinical Trial. JAMA Ophthalmol. 2022 Aug 1;140(8):771-778. doi: 10.1001/jamaophthalmol.2022.1091.
citation: Awh CC, Barteselli G, Makadia S, Chang RT, Stewart JM, Wieland MR, Brassard R, Callaway NF, Gune S, Heatherton P, Malhotra V, Willis JR, Pieramici DJ. Management of Key Ocular Adverse Events in Patients Implanted with the Port Delivery System with Ranibizumab. Ophthalmol Retina. 2022 Nov;6(11):1028-1043. doi: 10.1016/j.oret.2022.05.011. Epub 2022 May 16.
citation: Heimann F, Barteselli G, Brand A, Dingeldey A, Godard L, Hochstetter H, Schneider M, Rothkegel A, Wagner C, Horvath J, Ranade S. A custom virtual reality training solution for ophthalmologic surgical clinical trials. Adv Simul (Lond). 2021 Apr 16;6(1):12. doi: 10.1186/s41077-021-00167-z.