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 (Archway)

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 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).

Study Overview

• Status: Completed
• Conditions: Neovascular Age-Related Macular Degeneration
• Intervention / Treatment: Drug: PDS Implant filled with 100 mg/mL Ranibizumab; Drug: Intravitreal Injections of 10 mg/mL Ranibizumab

• Study Type: Interventional
• Enrollment (Actual): 415
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Mesa, Arizona, United States, 85206
      • Barnet Dulaney Perkins Eye Center
    • Phoenix, Arizona, United States, 85021
      • Arizona Retina and Vitreous Consultants
    • Phoenix, Arizona, United States, 85020
      • Associated Retina Consultants
    • Phoenix, Arizona, United States, 85053
      • Retinal Consultants of Arizona
  • California
    • Bakersfield, California, United States, 93309
      • California Retina Consultants
    • Beverly Hills, California, United States, 90211
      • Retina-Vitreous Associates Medical Group
    • Encino, California, United States, 91436
      • The Retina Partners
    • Los Angeles, California, United States, 90095-7000
      • Jules Stein Eye Institute/ UCLA
    • Mountain View, California, United States, 94040
      • N CA Retina Vitreous Assoc
    • Poway, California, United States, 92064
      • Retina Consultants, San Diego
    • Sacramento, California, United States, 95825
      • Retinal Consultants Med Group
    • San Francisco, California, United States, 94143
      • UCSF; Ophthalmology
    • San Francisco, California, United States, 94109
      • West Coast Retina Medical Group
    • Santa Ana, California, United States, 92705
      • Orange County Retina Med Group
    • Santa Barbara, California, United States, 93103
      • California Retina Consultants
    • Walnut Creek, California, United States, 94598
      • Bay Area Retina Associates
  • Colorado
    • Durango, Colorado, United States, 81303
      • Southwest Retina Consultants
    • Fort Collins, Colorado, United States, 80528
      • Eye Center of Northern CO
    • Lakewood, Colorado, United States, 80228
      • Colorado Retina Associates, PC
  • Connecticut
    • Waterford, Connecticut, United States, 06385
      • Retina Group of New England
  • Florida
    • Fort Myers, Florida, United States, 33912
      • National Ophthalmic Research Institute
    • Melbourne, Florida, United States, 32901
      • Florida Eye Associates
    • Palm Beach Gardens, Florida, United States, 33410
      • Retina Care Specialists
    • Pensacola, Florida, United States, 32503
      • Retina Specialty Institute
    • Plantation, Florida, United States, 33324
      • Fort Lauderdale Eye Institute
    • Saint Petersburg, Florida, United States, 33711
      • Retina Vitreous Assoc of FL
    • Tallahassee, Florida, United States, 32308
      • Southern Vitreoretinal Assoc
    • Tampa, Florida, United States, 33609
      • Retina Associates of Florida, LLC
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Southeast Retina Center
    • Marietta, Georgia, United States, 30060
      • Georgia Retina PC
  • Illinois
    • Joliet, Illinois, United States, 60435
      • Illinois Retina Associates
    • Lemont, Illinois, United States, 60439
      • University Retina and Macula Associates, PC
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Wolfe Eye Clinic
  • Kansas
    • Lenexa, Kansas, United States, 66215
      • Retina Associates
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Retina Associates of Kentucky
    • Paducah, Kentucky, United States, 42001
      • Paducah Retinal Center
  • Maine
    • Portland, Maine, United States, 04101
      • Maine Eye Center
  • Maryland
    • Baltimore, Maryland, United States, 21209
      • The Retina Care Center
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Med; Wilmer Eye Inst
    • Chevy Chase, Maryland, United States, 20815
      • Retina Group of Washington
    • Towson, Maryland, United States, 21204
      • Retina Specialists
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Ophthalmic Consultants of Boston
    • Worcester, Massachusetts, United States, 01605
      • Vitreo-Retinal Associates, PC
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Foundation for Vision Research
    • Grand Rapids, Michigan, United States, 49546
      • Associated Retinal Consultants
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • VitreoRetinal Surgery, PLLC.; DBA Retina Consultants of Minnesota
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • Midwest Vision Research Foundation
    • Chesterfield, Missouri, United States, 63017
      • The Retina Institute - Chesterfield
  • Nevada
    • Reno, Nevada, United States, 89502
      • Sierra Eye Associates
  • New Jersey
    • Bloomfield, New Jersey, United States, 07003
      • Envision Ocular, LLC
    • Cherry Hill, New Jersey, United States, 08034
      • Mid Atlantic Retina - Wills Eye Hospital
    • Toms River, New Jersey, United States, 08755
      • NJ Retina Teaneck Clinic
  • New York
    • Great Neck, New York, United States, 11021
      • Long Is. Vitreoretinal Consult
    • Liverpool, New York, United States, 13088
      • Retina Vit Surgeons/Central NY
    • New York, New York, United States, 10022
      • Vitreous-Retina-Macula
    • Rockville Centre, New York, United States, 11570
      • Ophthalmic Consultants of Long Island
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • Char Eye Ear &Throat Assoc
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Cincinnati Eye Institute
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43212
      • OSU Eye Physicians & Surgeons
  • Oklahoma
    • Edmond, Oklahoma, United States, 73013
      • Retina Vitreous Center
  • Oregon
    • Portland, Oregon, United States, 97221
      • Retina Northwest
  • South Carolina
    • Florence, South Carolina, United States, 29501
      • Palmetto Retina Center
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Charles Retina Institute
    • Nashville, Tennessee, United States, 37203
      • Tennessee Retina PC
  • Texas
    • Arlington, Texas, United States, 76012
      • Texas Retina Associates
    • Austin, Texas, United States, 78705
      • Austin Retina Associates
    • Austin, Texas, United States, 78750
      • Austin Clinical Research LLC
    • Bellaire, Texas, United States, 77401
      • Retina Consultants of Texas
    • Fort Worth, Texas, United States, 76104
      • Texas Retina Associates
    • San Antonio, Texas, United States, 78240
      • Med Center Ophthalmology Assoc
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Retina Associates of Utah
    • Salt Lake City, Utah, United States, 84107
      • Rocky Mountain Retina
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Wagner Macula & Retina Center
    • Richmond, Virginia, United States, 23235
      • Retina Institute of Virginia
  • Washington
    • Silverdale, Washington, United States, 98383
      • Retina Center Northwest
    • Spokane, Washington, United States, 99204
      • Spokane Eye Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: PDS Implant Arm; 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	Drug: PDS Implant filled with 100 mg/mL Ranibizumab; Will be administered as per the schedule described in individual arm.
ACTIVE_COMPARATOR: Intravitreal Arm; Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.	Drug: Intravitreal Injections of 10 mg/mL Ranibizumab; Will be administered as per the schedule described in individual arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 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
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 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 Lose <10 or <5 Letters in BCVA Score From Baseline 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 Who Gain ≥0 Letters in BCVA Score From Baseline Over Time		Baseline up to Week 96
Change From Baseline in Center Point Thickness (CPT) at Week 36		Baseline to Week 36
Change From Baseline in CPT Over Time		Baseline up 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 in the PDS Implant Arm Who Undergo a Supplemental Treatment That Requires Subsequent Additional Supplemental Treatments During the Study		Week 16 to Week 92
Percentage of Participants With Ocular and Systemic (Non-Ocular) AEs		Randomization to Week 96
Percentage of Participants With Adverse Events of Special Interest	Percentage of Participants with Adverse Events of Special Interest	Randomization to Week 96
Observed Serum Ranibizumab Concentrations at Specified Timepoints		Randomization to Week 96
Estimated PK Parameter Values AUC0-6M	AUC0-6M = Area Under the Concentration-Time Curve From 0 to 6 Months	Randomization to Week 96
Estimated PK Parameter Value t1/2 After PDS Implant Insertion	Apparent terminal half-life	Randomization to Week 96
Estimated PK Parameter Value Cmin	Cmin = Minimum Serum Concentration	Randomization to Week 96
Estimated PK Parameter Value Cmax	Cmax = Maximum Serum Concentration	Randomization to Week 96
Baseline Prevalence and Incidence of Treatment-Emergent ADA		Randomization to Week 96

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 12, 2018
• Primary Completion (ACTUAL): May 22, 2020
• Study Completion (ACTUAL): June 9, 2021

Study Registration Dates

• First Submitted: September 11, 2018
• First Submitted That Met QC Criteria: September 18, 2018
• First Posted (ACTUAL): September 19, 2018

Study Record Updates

• Last Update Posted (ACTUAL): October 4, 2022
• Last Update Submitted That Met QC Criteria: September 6, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Wet Macular Degeneration; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab
• Other Study ID Numbers: GR40548

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No