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

NCT ID: NCT03677934

Last Updated: 2022-10-04

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

415 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-09-12

Study Completion Date

2021-06-09

Brief Summary

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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

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Conditions

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Neovascular Age-Related Macular Degeneration

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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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

Group Type EXPERIMENTAL

PDS Implant filled with 100 mg/mL Ranibizumab

Intervention Type DRUG

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

Intravitreal Arm

Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.

Group Type ACTIVE_COMPARATOR

Intravitreal Injections of 10 mg/mL Ranibizumab

Intervention Type DRUG

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

Interventions

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PDS Implant filled with 100 mg/mL Ranibizumab

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

Intervention Type DRUG

Intravitreal Injections of 10 mg/mL Ranibizumab

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

Intervention Type DRUG

Eligibility Criteria

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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)
Minimum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Barnet Dulaney Perkins Eye Center

Mesa, Arizona, United States

Site Status

Associated Retina Consultants

Phoenix, Arizona, United States

Site Status

Arizona Retina and Vitreous Consultants

Phoenix, Arizona, United States

Site Status

Retinal Consultants of Arizona

Phoenix, Arizona, United States

Site Status

California Retina Consultants

Bakersfield, California, United States

Site Status

Retina-Vitreous Associates Medical Group

Beverly Hills, California, United States

Site Status

The Retina Partners

Encino, California, United States

Site Status

Jules Stein Eye Institute/ UCLA

Los Angeles, California, United States

Site Status

N CA Retina Vitreous Assoc

Mountain View, California, United States

Site Status

Retina Consultants, San Diego

Poway, California, United States

Site Status

Retinal Consultants Med Group

Sacramento, California, United States

Site Status

West Coast Retina Medical Group

San Francisco, California, United States

Site Status

UCSF; Ophthalmology

San Francisco, California, United States

Site Status

Orange County Retina Med Group

Santa Ana, California, United States

Site Status

California Retina Consultants

Santa Barbara, California, United States

Site Status

Bay Area Retina Associates

Walnut Creek, California, United States

Site Status

Southwest Retina Consultants

Durango, Colorado, United States

Site Status

Eye Center of Northern CO

Fort Collins, Colorado, United States

Site Status

Colorado Retina Associates, PC

Lakewood, Colorado, United States

Site Status

Retina Group of New England

Waterford, Connecticut, United States

Site Status

National Ophthalmic Research Institute

Fort Myers, Florida, United States

Site Status

Florida Eye Associates

Melbourne, Florida, United States

Site Status

Retina Care Specialists

Palm Beach Gardens, Florida, United States

Site Status

Retina Specialty Institute

Pensacola, Florida, United States

Site Status

Fort Lauderdale Eye Institute

Plantation, Florida, United States

Site Status

Retina Vitreous Assoc of FL

St. Petersburg, Florida, United States

Site Status

Southern Vitreoretinal Assoc

Tallahassee, Florida, United States

Site Status

Retina Associates of Florida, LLC

Tampa, Florida, United States

Site Status

Southeast Retina Center

Augusta, Georgia, United States

Site Status

Georgia Retina PC

Marietta, Georgia, United States

Site Status

Illinois Retina Associates

Joliet, Illinois, United States

Site Status

University Retina and Macula Associates, PC

Lemont, Illinois, United States

Site Status

Wolfe Eye Clinic

West Des Moines, Iowa, United States

Site Status

Retina Associates

Lenexa, Kansas, United States

Site Status

Retina Associates of Kentucky

Lexington, Kentucky, United States

Site Status

Paducah Retinal Center

Paducah, Kentucky, United States

Site Status

Maine Eye Center

Portland, Maine, United States

Site Status

The Retina Care Center

Baltimore, Maryland, United States

Site Status

Johns Hopkins Med; Wilmer Eye Inst

Baltimore, Maryland, United States

Site Status

Retina Group of Washington

Chevy Chase, Maryland, United States

Site Status

Retina Specialists

Towson, Maryland, United States

Site Status

Ophthalmic Consultants of Boston

Boston, Massachusetts, United States

Site Status

Vitreo-Retinal Associates, PC

Worcester, Massachusetts, United States

Site Status

Associated Retinal Consultants

Grand Rapids, Michigan, United States

Site Status

Foundation for Vision Research

Grand Rapids, Michigan, United States

Site Status

VitreoRetinal Surgery, PLLC.; DBA Retina Consultants of Minnesota

Edina, Minnesota, United States

Site Status

Midwest Vision Research Foundation

Chesterfield, Missouri, United States

Site Status

The Retina Institute - Chesterfield

Chesterfield, Missouri, United States

Site Status

Sierra Eye Associates

Reno, Nevada, United States

Site Status

Envision Ocular, LLC

Bloomfield, New Jersey, United States

Site Status

Mid Atlantic Retina - Wills Eye Hospital

Cherry Hill, New Jersey, United States

Site Status

NJ Retina Teaneck Clinic

Toms River, New Jersey, United States

Site Status

Long Is. Vitreoretinal Consult

Great Neck, New York, United States

Site Status

Retina Vit Surgeons/Central NY

Liverpool, New York, United States

Site Status

Vitreous-Retina-Macula

New York, New York, United States

Site Status

Ophthalmic Consultants of Long Island

Rockville Centre, New York, United States

Site Status

Char Eye Ear &Throat Assoc

Charlotte, North Carolina, United States

Site Status

Cincinnati Eye Institute

Cincinnati, Ohio, United States

Site Status

The Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

OSU Eye Physicians & Surgeons

Columbus, Ohio, United States

Site Status

Retina Vitreous Center

Edmond, Oklahoma, United States

Site Status

Retina Northwest

Portland, Oregon, United States

Site Status

Palmetto Retina Center

Florence, South Carolina, United States

Site Status

Charles Retina Institute

Memphis, Tennessee, United States

Site Status

Tennessee Retina PC

Nashville, Tennessee, United States

Site Status

Texas Retina Associates

Arlington, Texas, United States

Site Status

Austin Retina Associates

Austin, Texas, United States

Site Status

Austin Clinical Research LLC

Austin, Texas, United States

Site Status

Retina Consultants of Texas

Bellaire, Texas, United States

Site Status

Texas Retina Associates

Fort Worth, Texas, United States

Site Status

Med Center Ophthalmology Assoc

San Antonio, Texas, United States

Site Status

Retina Associates of Utah

Salt Lake City, Utah, United States

Site Status

Rocky Mountain Retina

Salt Lake City, Utah, United States

Site Status

Wagner Macula & Retina Center

Norfolk, Virginia, United States

Site Status

Retina Institute of Virginia

Richmond, Virginia, United States

Site Status

Retina Center Northwest

Silverdale, Washington, United States

Site Status

Spokane Eye Clinical Research

Spokane, Washington, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 39447871 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39209113 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39154860 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38914294 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35708706 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35589078 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33863399 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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GR40548

Identifier Type: -

Identifier Source: org_study_id

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