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

Neovascular Age-Related Macular Degeneration Clinical Trial

— Archway  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03677934
• Other study ID #: GR40548
• Status: Completed
• Phase: Phase 3
• Start date: September 12, 2018
• Est. completion date: June 9, 2021

Study information

• Verified date: September 2022
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 415
• Est. completion date: June 9, 2021
• Est. primary completion date: May 22, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Macular Degeneration
• Neovascular Age-Related Macular Degeneration
• Wet Macular Degeneration

Intervention

Drug:
• PDS Implant filled with 100 mg/mL Ranibizumab
Will be administered as per the schedule described in individual arm.
• Intravitreal Injections of 10 mg/mL Ranibizumab
Will be administered as per the schedule described in individual arm.

Locations

Country	Name	City	State
United States	Texas Retina Associates	Arlington	Texas
United States	Southeast Retina Center	Augusta	Georgia
United States	Austin Clinical Research LLC	Austin	Texas
United States	Austin Retina Associates	Austin	Texas
United States	California Retina Consultants	Bakersfield	California
United States	Johns Hopkins Med; Wilmer Eye Inst	Baltimore	Maryland
United States	The Retina Care Center	Baltimore	Maryland
United States	Retina Consultants of Texas	Bellaire	Texas
United States	Retina-Vitreous Associates Medical Group	Beverly Hills	California
United States	Envision Ocular, LLC	Bloomfield	New Jersey
United States	Ophthalmic Consultants of Boston	Boston	Massachusetts
United States	Char Eye Ear &Throat Assoc	Charlotte	North Carolina
United States	Mid Atlantic Retina - Wills Eye Hospital	Cherry Hill	New Jersey
United States	Midwest Vision Research Foundation	Chesterfield	Missouri
United States	The Retina Institute - Chesterfield	Chesterfield	Missouri
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	OSU Eye Physicians & Surgeons	Columbus	Ohio
United States	Southwest Retina Consultants	Durango	Colorado
United States	VitreoRetinal Surgery, PLLC.; DBA Retina Consultants of Minnesota	Edina	Minnesota
United States	Retina Vitreous Center	Edmond	Oklahoma
United States	The Retina Partners	Encino	California
United States	Palmetto Retina Center	Florence	South Carolina
United States	Eye Center of Northern CO	Fort Collins	Colorado
United States	National Ophthalmic Research Institute	Fort Myers	Florida
United States	Texas Retina Associates	Fort Worth	Texas
United States	Associated Retinal Consultants	Grand Rapids	Michigan
United States	Foundation for Vision Research	Grand Rapids	Michigan
United States	Long Is. Vitreoretinal Consult	Great Neck	New York
United States	Illinois Retina Associates	Joliet	Illinois
United States	Colorado Retina Associates, PC	Lakewood	Colorado
United States	University Retina and Macula Associates, PC	Lemont	Illinois
United States	Retina Associates	Lenexa	Kansas
United States	Retina Associates of Kentucky	Lexington	Kentucky
United States	Retina Vit Surgeons/Central NY	Liverpool	New York
United States	Jules Stein Eye Institute/ UCLA	Los Angeles	California
United States	Georgia Retina PC	Marietta	Georgia
United States	Florida Eye Associates	Melbourne	Florida
United States	Charles Retina Institute	Memphis	Tennessee
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	Vitreous-Retina-Macula	New York	New York
United States	Wagner Macula & Retina Center	Norfolk	Virginia
United States	Paducah Retinal Center	Paducah	Kentucky
United States	Retina Care Specialists	Palm Beach Gardens	Florida
United States	Retina Specialty Institute	Pensacola	Florida
United States	Arizona Retina and Vitreous Consultants	Phoenix	Arizona
United States	Associated Retina Consultants	Phoenix	Arizona
United States	Retinal Consultants of Arizona	Phoenix	Arizona
United States	Fort Lauderdale Eye Institute	Plantation	Florida
United States	Maine Eye Center	Portland	Maine
United States	Retina Northwest	Portland	Oregon
United States	Retina Consultants, San Diego	Poway	California
United States	Sierra Eye Associates	Reno	Nevada
United States	Retina Institute of Virginia	Richmond	Virginia
United States	Ophthalmic Consultants of Long Island	Rockville Centre	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	Rocky Mountain Retina	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 Center Northwest	Silverdale	Washington
United States	Spokane Eye Clinical Research	Spokane	Washington
United States	Southern Vitreoretinal Assoc	Tallahassee	Florida
United States	Retina Associates of Florida, LLC	Tampa	Florida
United States	NJ Retina Teaneck Clinic	Toms River	New Jersey
United States	Retina Specialists	Towson	Maryland
United States	Bay Area Retina Associates	Walnut Creek	California
United States	Retina Group of New England	Waterford	Connecticut
United States	Wolfe Eye Clinic	West Des Moines	Iowa
United States	Vitreo-Retinal Associates, PC	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Baseline, and the average of Week 36 and Week 40
Secondary	Change From Baseline in BCVA Score Averaged Over Week 60 and Week 64		Baseline, Week60, Week 64
Secondary	Change From Baseline in BCVA Score Over Time		Baseline up to Week 96
Secondary	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
Secondary	Percentage of Participants With BCVA Score of 38 Letters (20/200 Approximate Snellen Equivalent) or Worse Over Time		Baseline up to Week 96
Secondary	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
Secondary	Percentage of Participants With BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better Over Time		Baseline up to Week 96
Secondary	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
Secondary	Percentage of Participants Who Lose <10 or <5 Letters in BCVA Score From Baseline Over Time		Baseline up to Week 96
Secondary	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
Secondary	Percentage of Participants Who Gain =0 Letters in BCVA Score From Baseline Over Time		Baseline up to Week 96
Secondary	Change From Baseline in Center Point Thickness (CPT) at Week 36		Baseline to Week 36
Secondary	Change From Baseline in CPT Over Time		Baseline up to Week 96
Secondary	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
Secondary	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
Secondary	Percentage of Participants With Ocular and Systemic (Non-Ocular) AEs		Randomization to Week 96
Secondary	Percentage of Participants With Adverse Events of Special Interest	Percentage of Participants with Adverse Events of Special Interest	Randomization to Week 96
Secondary	Observed Serum Ranibizumab Concentrations at Specified Timepoints		Randomization to Week 96
Secondary	Estimated PK Parameter Values AUC0-6M	AUC0-6M = Area Under the Concentration-Time Curve From 0 to 6 Months	Randomization to Week 96
Secondary	Estimated PK Parameter Value t1/2 After PDS Implant Insertion	Apparent terminal half-life	Randomization to Week 96
Secondary	Estimated PK Parameter Value Cmin	Cmin = Minimum Serum Concentration	Randomization to Week 96
Secondary	Estimated PK Parameter Value Cmax	Cmax = Maximum Serum Concentration	Randomization to Week 96
Secondary	Baseline Prevalence and Incidence of Treatment-Emergent ADA		Randomization to Week 96