NCT03677934

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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
415

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Sep 2018

Typical duration for phase_3

Geographic Reach
1 country

77 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 11, 2018

Completed
1 day until next milestone

Study Start

First participant enrolled

September 12, 2018

Completed
7 days until next milestone

First Posted

Study publicly available on registry

September 19, 2018

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 22, 2020

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

June 9, 2021

Completed
10 months until next milestone

Results Posted

Study results publicly available

March 25, 2022

Completed
Last Updated

October 4, 2022

Status Verified

September 1, 2022

Enrollment Period

1.7 years

First QC Date

September 11, 2018

Results QC Date

November 18, 2021

Last Update Submit

September 6, 2022

Conditions

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (22)

  • 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

  • +17 more secondary outcomes

Study Arms (2)

PDS Implant Arm

EXPERIMENTAL

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

Intravitreal Arm

ACTIVE COMPARATOR

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

Interventions

Will be administered as per the schedule described in individual arm.

PDS Implant Arm

Will be administered as per the schedule described in individual arm.

Intravitreal Arm

Eligibility Criteria

Age50 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (77)

Barnet Dulaney Perkins Eye Center

Mesa, Arizona, 85206, United States

Location

Associated Retina Consultants

Phoenix, Arizona, 85020, United States

Location

Arizona Retina and Vitreous Consultants

Phoenix, Arizona, 85021, United States

Location

Retinal Consultants of Arizona

Phoenix, Arizona, 85053, United States

Location

California Retina Consultants

Bakersfield, California, 93309, United States

Location

Retina-Vitreous Associates Medical Group

Beverly Hills, California, 90211, United States

Location

The Retina Partners

Encino, California, 91436, United States

Location

Jules Stein Eye Institute/ UCLA

Los Angeles, California, 90095-7000, United States

Location

N CA Retina Vitreous Assoc

Mountain View, California, 94040, United States

Location

Retina Consultants, San Diego

Poway, California, 92064, United States

Location

Retinal Consultants Med Group

Sacramento, California, 95825, United States

Location

West Coast Retina Medical Group

San Francisco, California, 94109, United States

Location

UCSF; Ophthalmology

San Francisco, California, 94143, United States

Location

Orange County Retina Med Group

Santa Ana, California, 92705, United States

Location

California Retina Consultants

Santa Barbara, California, 93103, United States

Location

Bay Area Retina Associates

Walnut Creek, California, 94598, United States

Location

Southwest Retina Consultants

Durango, Colorado, 81303, United States

Location

Eye Center of Northern CO

Fort Collins, Colorado, 80528, United States

Location

Colorado Retina Associates, PC

Lakewood, Colorado, 80228, United States

Location

Retina Group of New England

Waterford, Connecticut, 06385, United States

Location

National Ophthalmic Research Institute

Fort Myers, Florida, 33912, United States

Location

Florida Eye Associates

Melbourne, Florida, 32901, United States

Location

Retina Care Specialists

Palm Beach Gardens, Florida, 33410, United States

Location

Retina Specialty Institute

Pensacola, Florida, 32503, United States

Location

Fort Lauderdale Eye Institute

Plantation, Florida, 33324, United States

Location

Retina Vitreous Assoc of FL

St. Petersburg, Florida, 33711, United States

Location

Southern Vitreoretinal Assoc

Tallahassee, Florida, 32308, United States

Location

Retina Associates of Florida, LLC

Tampa, Florida, 33609, United States

Location

Southeast Retina Center

Augusta, Georgia, 30909, United States

Location

Georgia Retina PC

Marietta, Georgia, 30060, United States

Location

Illinois Retina Associates

Joliet, Illinois, 60435, United States

Location

University Retina and Macula Associates, PC

Lemont, Illinois, 60439, United States

Location

Wolfe Eye Clinic

West Des Moines, Iowa, 50266, United States

Location

Retina Associates

Lenexa, Kansas, 66215, United States

Location

Retina Associates of Kentucky

Lexington, Kentucky, 40509, United States

Location

Paducah Retinal Center

Paducah, Kentucky, 42001, United States

Location

Maine Eye Center

Portland, Maine, 04101, United States

Location

The Retina Care Center

Baltimore, Maryland, 21209, United States

Location

Johns Hopkins Med; Wilmer Eye Inst

Baltimore, Maryland, 21287, United States

Location

Retina Group of Washington

Chevy Chase, Maryland, 20815, United States

Location

Retina Specialists

Towson, Maryland, 21204, United States

Location

Ophthalmic Consultants of Boston

Boston, Massachusetts, 02114, United States

Location

Vitreo-Retinal Associates, PC

Worcester, Massachusetts, 01605, United States

Location

Associated Retinal Consultants

Grand Rapids, Michigan, 49546, United States

Location

Foundation for Vision Research

Grand Rapids, Michigan, 49546, United States

Location

VitreoRetinal Surgery, PLLC.; DBA Retina Consultants of Minnesota

Edina, Minnesota, 55435, United States

Location

Midwest Vision Research Foundation

Chesterfield, Missouri, 63017, United States

Location

The Retina Institute - Chesterfield

Chesterfield, Missouri, 63017, United States

Location

Sierra Eye Associates

Reno, Nevada, 89502, United States

Location

Envision Ocular, LLC

Bloomfield, New Jersey, 07003, United States

Location

Mid Atlantic Retina - Wills Eye Hospital

Cherry Hill, New Jersey, 08034, United States

Location

NJ Retina Teaneck Clinic

Toms River, New Jersey, 08755, United States

Location

Long Is. Vitreoretinal Consult

Great Neck, New York, 11021, United States

Location

Retina Vit Surgeons/Central NY

Liverpool, New York, 13088, United States

Location

Vitreous-Retina-Macula

New York, New York, 10022, United States

Location

Ophthalmic Consultants of Long Island

Rockville Centre, New York, 11570, United States

Location

Char Eye Ear &Throat Assoc

Charlotte, North Carolina, 28210, United States

Location

Cincinnati Eye Institute

Cincinnati, Ohio, 45242, United States

Location

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

OSU Eye Physicians & Surgeons

Columbus, Ohio, 43212, United States

Location

Retina Vitreous Center

Edmond, Oklahoma, 73013, United States

Location

Retina Northwest

Portland, Oregon, 97221, United States

Location

Palmetto Retina Center

Florence, South Carolina, 29501, United States

Location

Charles Retina Institute

Memphis, Tennessee, 38119, United States

Location

Tennessee Retina PC

Nashville, Tennessee, 37203, United States

Location

Texas Retina Associates

Arlington, Texas, 76012, United States

Location

Austin Retina Associates

Austin, Texas, 78705, United States

Location

Austin Clinical Research LLC

Austin, Texas, 78750, United States

Location

Retina Consultants of Texas

Bellaire, Texas, 77401, United States

Location

Texas Retina Associates

Fort Worth, Texas, 76104, United States

Location

Med Center Ophthalmology Assoc

San Antonio, Texas, 78240, United States

Location

Retina Associates of Utah

Salt Lake City, Utah, 84107, United States

Location

Rocky Mountain Retina

Salt Lake City, Utah, 84107, United States

Location

Wagner Macula & Retina Center

Norfolk, Virginia, 23502, United States

Location

Retina Institute of Virginia

Richmond, Virginia, 23235, United States

Location

Retina Center Northwest

Silverdale, Washington, 98383, United States

Location

Spokane Eye Clinical Research

Spokane, Washington, 99204, United States

Location

Related Publications (7)

  • Sheth VS, Holekamp NM, Khanani AM, Rachitskaya A, Blotner S, Gune S, Heinrich D, Maass KF, Chakravarthy U. Retinal Fluid and Thickness Fluctuations in Archway Trial for Port Delivery System with Ranibizumab versus Monthly Ranibizumab Injections. Ophthalmol Retina. 2025 Apr;9(4):330-342. doi: 10.1016/j.oret.2024.10.015. Epub 2024 Oct 22.

  • Campochiaro PA, Eichenbaum D, Chang MA, Clark WL, Graff JM, Le Pogam S, Cavichini Cordeiro M, Gune S, Rabena M, Singh N, Lin S, Callaway N. Interim Results of the Phase III Portal Extension Trial of the Port Delivery System with Ranibizumab in Neovascular Age-Related Macular Degeneration. Ophthalmol Retina. 2025 Feb;9(2):144-155. doi: 10.1016/j.oret.2024.05.021. Epub 2024 Aug 30.

  • Eichenbaum DA, Freeman WR, Chang MA, Brooks L, Chaudhry N, Dadgostar H, McCannel CA, Michels M, Mittra RA, Wolfe JD, Beindl VC, Jaycock P, Bobbala A, Gune S, Spicer G, Callaway N. Endophthalmitis in Eyes Treated with the Port Delivery System with Ranibizumab: Summary of Cases during Clinical Trial Development. Ophthalmol Retina. 2025 Feb;9(2):127-143. doi: 10.1016/j.oret.2024.08.005. Epub 2024 Aug 16.

  • Nielsen JS, Chang A, Holekamp NM, Cavichini-Cordeiro M, Lin SL, Heinrich D, Maass KF, Menezes A, Singh N, Pieramici DJ. Supplemental Intravitreal Ranibizumab Injections in Eyes Treated with the Port Delivery System with Ranibizumab in the Archway Trial. Ophthalmol Retina. 2024 Dec;8(12):1127-1139. doi: 10.1016/j.oret.2024.06.012. Epub 2024 Jun 22.

  • 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.

MeSH Terms

Interventions

Ranibizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Results Point of Contact

Title
Medical Communications
Organization
Hoffmann-La Roche

Study Officials

  • Clinical Trials

    Hoffmann-La Roche

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 11, 2018

First Posted

September 19, 2018

Study Start

September 12, 2018

Primary Completion

May 22, 2020

Study Completion

June 9, 2021

Last Updated

October 4, 2022

Results First Posted

March 25, 2022

Record last verified: 2022-09

Data Sharing

IPD Sharing
Will share

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).

Locations