A Study to Evaluate Efficacy, Safety & Pharmacokinetics of the Port Delivery System (PDS) With Ranibizumab in Participants With Diabetic Macular Edema (DME) Compared With Intravitreal Ranibizumab; A Substudy to Evaluate the Safety of Re-implanting the PDS With Ranibizumab in Participants With DME

NCT ID: NCT04108156

Last Updated: 2026-01-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

634 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-09-30

Study Completion Date

2027-11-16

Brief Summary

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This study will evaluate the efficacy, safety, and Pharmacokinetics (PK) of the PDS with ranibizumab in participants with DME when treated every 24 weeks (Q24W) compared with intravitreal (IVT) ranibizumab 0.5 milligrams (mg) every 4 weeks (Q4W).

The substudy will evaluate safety of re-implanting the updated PDS with ranibizumab and the refill-exchange procedures following re-implantation in participants with DME who were previously enrolled in the main study, GR40550. Up to 100 participants from the main study will be enrolled and followed for a maximum of 72 weeks post-re-implantation in the substudy.

Detailed Description

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Conditions

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Diabetic Macular Edema

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
The substudy is a non-randomized, open-label study.

Study Groups

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PDS Arm

Participants randomized to the PDS arm will receive IVT ranibizumab injection Q4W (loading phase) and will then have the PDS implant (pre-filled with ranibizumab) surgically inserted. PDS implant refill-exchange procedures will be performed on a fixed interval Q24W thereafter.

Group Type EXPERIMENTAL

PDS Implant Pre-Filled with 100 mg/mL Ranibizumab

Intervention Type DRUG

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

Ranibizumab refill exchange

Intervention Type DRUG

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

Intravitreal Arm

Participants randomized to the intravitreal arm will receive IVT ranibizumab injection Q4W until they receive the PDS implant (pre-filled with ranibizumab). PDS implant refill-exchange procedures will be performed on a fixed interval Q24W thereafter.

Group Type ACTIVE_COMPARATOR

Intravitreal Ranibizumab 0.5 mg Injection

Intervention Type DRUG

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

Ranibizumab refill exchange

Intervention Type DRUG

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

Substudy: Cohort 1

Participants will undergo re-implantation with the updated PDS implant (pre-filled with ranibizumab 100 milligrams per milliliter \[mg/mL\]) on Day 1 (or enrollment visit) and then will have two refill-exchanges (ranibizumab 100 mg/mL) Q24W up to 48 weeks.

Group Type EXPERIMENTAL

PDS Implant Pre-Filled with 100 mg/mL Ranibizumab

Intervention Type DRUG

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

Ranibizumab refill exchange

Intervention Type DRUG

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

Substudy: Cohort 2a

Participants who received an updated PDS implant, have \< 24 weeks post-re-implantation follow-up and no scheduled refill-exchange visit in the main study, will undergo two refill-exchange procedures (ranibizumab 100 mg/mL) Q24W, post main study re-implantation visit.

Group Type EXPERIMENTAL

Ranibizumab refill exchange

Intervention Type DRUG

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

Substudy: Cohort 2b

Participants who received an updated PDS implant, have \< 48 weeks post-re-implantation follow-up and one refill exchange visit in the main study, regardless of whether the refill exchange was administered or the visit was missed, will undergo one refill-exchange procedure (ranibizumab 100 mg/mL) Q24W, post main study re-implantation visit.

Group Type EXPERIMENTAL

Ranibizumab refill exchange

Intervention Type DRUG

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

Interventions

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PDS Implant Pre-Filled with 100 mg/mL Ranibizumab

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

Intervention Type DRUG

Intravitreal Ranibizumab 0.5 mg Injection

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

Intervention Type DRUG

Ranibizumab refill exchange

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Age ≥18 years at time of signing informed consent form (ICF)
* Documented diagnosis of diabetes mellitus (Type 1 or Type 2)
* Glycated haemoglobin (HbA1c) level of ≤10% within 2 months prior to screening or at screening

Study eye

* Macular thickening secondary to DME involving the center of the fovea with CST ≥325 micrometer (µm) on SD-OCT at screening
* BCVA score of 78 to 25 letters (20/32 to 20/320 approximate Snellen equivalent)


* Having experienced a septum dislodgement in the original implant while in the main study or after exiting the main study
* Sufficiently clear ocular media and adequate pupillary dilation to allow for analysis and grading by central reading center

Exclusion Criteria

* High-risk PDR
* Active intraocular inflammation (grade trace or above)
* Suspected or active ocular or periocular infection of either eye
* Uncontrolled ocular hypertension or glaucoma and any such condition the investigator determines may require a glaucoma-filtering surgery during a patient's participation in the study
* Cerebrovascular accident or myocardial infarction within 6 months prior to randomization
* Atrial fibrillation diagnosis or worsening within 6 months prior to randomization
* Uncontrolled blood pressure

Substudy:


* Recent history (in the last 3 months prior to enrollment) of other disease, other non-diabetic metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a condition that contraindicates the use of ranibizumab or surgical placement of the PDS implant; that might affect interpretation of the results of the study; or that renders the participant at high risk for treatment complications
* Active cancer within the last 12 months, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or prostate cancer
* Current systemic treatment for a confirmed active systemic infection
* Participation in an investigational trial that involves treatment with any drug or device (with the exception of vitamins and minerals or enrollment in Study GR40550) within 6 months prior to enrollment
* Use of antimitotic or antimetabolite therapy within 30 days


* Any ocular condition that may render the participant at high risk for surgical or treatment complications
* Intraocular surgery (including cataract surgery) within 1 month preceding the enrollment visit
* Any use of medicated intraocular implants (other than the PDS implant), at any time prior to enrollment
* History of rhegmatogenous retinal tears or peripheral retinal breaks within 3 months prior to the enrollment visit
* Any concurrent ocular condition that would require surgical intervention during the study to prevent or treat visual loss
* Concurrent conjunctival, tenon's capsule, and/or scleral condition in the supero-temporal quadrant of the eye (e.g., scarring, thinning, mass) that may affect the refill-exchange procedure of the PDS implant
* Suspected or active ocular or periocular infection (e.g., infectious conjunctivitis or endophthalmitis)
* Any history of uveitis
* Active blepharitis
Minimum Eligible Age

18 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 COMPLETED

Retinal Consultants of Arizona;Opthalmology

Phoenix, Arizona, United States

Site Status COMPLETED

Arizona Retina and Vitreous Consultants

Phoenix, Arizona, United States

Site Status COMPLETED

Associated Retina Consultants

Phoenix, Arizona, United States

Site Status COMPLETED

California Retina Consultants

Bakersfield, California, United States

Site Status RECRUITING

Retina-Vitreous Associates Medical Group

Beverly Hills, California, United States

Site Status COMPLETED

The Retina Partners

Encino, California, United States

Site Status COMPLETED

Retina Consultants of Orange County;Clinical Research

Fullerton, California, United States

Site Status RECRUITING

Jules Stein Eye Institute/ UCLA

Los Angeles, California, United States

Site Status COMPLETED

Northern California Retina-Vitreous Associates

Mountain View, California, United States

Site Status COMPLETED

East Bay Retina Consultants

Oakland, California, United States

Site Status RECRUITING

Doheny Eye Institute

Pasadena, California, United States

Site Status COMPLETED

California Eye Specialists Medical Group

Pasadena, California, United States

Site Status COMPLETED

Retina Consultants Medical Group

Sacramento, California, United States

Site Status RECRUITING

Zuckerberg San Francisco General Hospital and Trauma Center

San Francisco, California, United States

Site Status COMPLETED

Orange County Retina Medical Group

Santa Ana, California, United States

Site Status RECRUITING

California Retina Consultants;Research Department

Santa Barbara, California, United States

Site Status COMPLETED

Eye Center of Northern Colorado

Fort Collins, Colorado, United States

Site Status COMPLETED

Colorado Clinical Research

Lakewood, Colorado, United States

Site Status COMPLETED

Retina Group of New England

Waterford, Connecticut, United States

Site Status ACTIVE_NOT_RECRUITING

Retina Group of Florida

Fort Lauderdale, Florida, United States

Site Status COMPLETED

National Ophthalmic Research Institute

Fort Myers, Florida, United States

Site Status COMPLETED

Retina Specialty Institute

Pensacola, Florida, United States

Site Status RECRUITING

Fort Lauderdale Eye Institute

Plantation, Florida, United States

Site Status RECRUITING

Retina Vitreous Associates of Florida

St. Petersburg, Florida, United States

Site Status RECRUITING

Southern Vitreoretinal Associates;Research

Tallahassee, Florida, United States

Site Status WITHDRAWN

Retina Associates of Florida;Retina Associates of Florida

Tampa, Florida, United States

Site Status COMPLETED

Southeast Retina Center

Augusta, Georgia, United States

Site Status RECRUITING

Georgia Retina

Marietta, Georgia, United States

Site Status COMPLETED

Northwestern Memorial Hospital

Chicago, Illinois, United States

Site Status COMPLETED

Illinois Retina Associates

Joliet, Illinois, United States

Site Status COMPLETED

University Retina

Lemont, Illinois, United States

Site Status COMPLETED

Wolfe Eye Clinic

West Des Moines, Iowa, United States

Site Status COMPLETED

Retina Associates

Lenexa, Kansas, United States

Site Status COMPLETED

Retina & Vitreous Associates of Kentucky

Lexington, Kentucky, United States

Site Status COMPLETED

Maine Eye Center

Portland, Maine, United States

Site Status ACTIVE_NOT_RECRUITING

The Retina Care Center

Baltimore, Maryland, United States

Site Status COMPLETED

Johns Hopkins Hospital;Johns Hopkins Med;Wilmer Eye Inst

Baltimore, Maryland, United States

Site Status COMPLETED

The Retina Group of Washington;Retinal Disease

Chevy Chase, Maryland, United States

Site Status RECRUITING

Cumberland Valley Retina Consultants;Clinical Research

Hagerstown, Maryland, United States

Site Status RECRUITING

Retina Specialist

Towson, Maryland, United States

Site Status COMPLETED

Tufts Medical Center

Boston, Massachusetts, United States

Site Status ACTIVE_NOT_RECRUITING

Ophthalmic Consultants of Boston

Boston, Massachusetts, United States

Site Status COMPLETED

Vitreo Retinal Associates

Worcester, Massachusetts, United States

Site Status COMPLETED

Retina Specialists Of Michigan

Grand Rapids, Michigan, United States

Site Status COMPLETED

Associated Retinal Consultants - Royal Oak

Royal Oak, Michigan, United States

Site Status COMPLETED

VitreoRetinal Surgery PLLC;DBA Retina Consultants of Minnesota

Minneapolis, Minnesota, United States

Site Status COMPLETED

Pepose Vision Institute

Chesterfield, Missouri, United States

Site Status COMPLETED

Retina Institute

St Louis, Missouri, United States

Site Status COMPLETED

Sierra Eye Associates

Reno, Nevada, United States

Site Status RECRUITING

Envision Ocular, LLC

Bloomfield, New Jersey, United States

Site Status COMPLETED

Retina Associates of New Jersey

Teaneck, New Jersey, United States

Site Status ACTIVE_NOT_RECRUITING

Long Island Vitreoretinal Consultants;Opthalmology

Great Neck, New York, United States

Site Status COMPLETED

Retina Vitreous Surgeons of Central New York

Liverpool, New York, United States

Site Status WITHDRAWN

New York University (NYU)

New York, New York, United States

Site Status COMPLETED

Ophthalmic Consultants of Long Island

Oceanside, New York, United States

Site Status COMPLETED

Asheville Eye Associates Western Carolina Retinal Associates;Clinical Research

Asheville, North Carolina, United States

Site Status COMPLETED

Charlotte Eye Ear Nose and Throat Associates- SouthPark;Retina

Charlotte, North Carolina, United States

Site Status COMPLETED

Duke Eye Center

Durham, North Carolina, United States

Site Status COMPLETED

Graystone Eye;Clinical Research

Hickory, North Carolina, United States

Site Status COMPLETED

Cape Fear Retinal Associates

Wilmington, North Carolina, United States

Site Status WITHDRAWN

Cincinnati Eye Institute;Retina

Cincinnati, Ohio, United States

Site Status RECRUITING

Cleveland Clinic

Cleveland, Ohio, United States

Site Status COMPLETED

Ohio State Havener Eye Institute;Ophthalmology Research

Columbus, Ohio, United States

Site Status RECRUITING

Midwest Retina;Retina/Vitreous

Dublin, Ohio, United States

Site Status COMPLETED

Retina Vitreous Center - Glen Eagles

Edmond, Oklahoma, United States

Site Status COMPLETED

Retina Northwest;Research Department

Portland, Oregon, United States

Site Status COMPLETED

Cumberland Valley Retina Consultants

Chambersburg, Pennsylvania, United States

Site Status WITHDRAWN

Mid Atlantic Retina

Philadelphia, Pennsylvania, United States

Site Status COMPLETED

Charleston Neuroscience

Ladson, South Carolina, United States

Site Status COMPLETED

Carolina Eyecare Physicians

Mt. Pleasant, South Carolina, United States

Site Status COMPLETED

Palmetto Retina Center

West Columbia, South Carolina, United States

Site Status COMPLETED

Palmetto Retina Center

West Columbia, South Carolina, United States

Site Status WITHDRAWN

Charles Retina Institution;Retina surgery

Germantown, Tennessee, United States

Site Status WITHDRAWN

Tennessee Retina

Nashville, Tennessee, United States

Site Status ACTIVE_NOT_RECRUITING

Retina Research Institute of Texas

Abilene, Texas, United States

Site Status COMPLETED

Texas Retina Associates

Arlington, Texas, United States

Site Status COMPLETED

Austin Research Center for Retina

Austin, Texas, United States

Site Status COMPLETED

Austin Retina Associates;Opthalmology

Austin, Texas, United States

Site Status COMPLETED

Austin Clinical Research, LLC

Austin, Texas, United States

Site Status COMPLETED

Retina & Vitreous of Texas

Bellaire, Texas, United States

Site Status WITHDRAWN

Texas Retina Associates;Research

Dallas, Texas, United States

Site Status COMPLETED

Texas Retina Associates

Fort Worth, Texas, United States

Site Status COMPLETED

Retina Consultants of Texas

Houston, Texas, United States

Site Status RECRUITING

Medical Center Ophthalmology Associates

San Antonio, Texas, United States

Site Status RECRUITING

Rocky Mountain Retina Consultants

Murray, Utah, United States

Site Status COMPLETED

Retina Associates of Utah, PLLC;Clinical Research

Salt Lake City, Utah, United States

Site Status COMPLETED

Piedmont Eye Center

Lynchburg, Virginia, United States

Site Status COMPLETED

Wagner Kapoor Institute;Opthalmology

Norfolk, Virginia, United States

Site Status COMPLETED

Retina Institute of Virginia

Richmond, Virginia, United States

Site Status RECRUITING

Pacific Northwest Retina

Silverdale, Washington, United States

Site Status COMPLETED

Spokane Eye Clinical Research;Spokane Eye Surgery Center

Spokane, Washington, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Reference Study ID Number: GR40550 https://forpatients.roche.com/

Role: CONTACT

888-662-6728 (U.S. and Canada)

References

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Khanani AM, Campochiaro PA, Graff JM, Marcus DM, Miller D, Mittra RA, Regillo C, Sheth VS, Bobbala A, Gune S, Lin S, Quezada-Ruiz C, Malhotra V. Continuous Ranibizumab via Port Delivery System vs Monthly Ranibizumab for Treatment of Diabetic Macular Edema: The Pagoda Randomized Clinical Trial. JAMA Ophthalmol. 2025 Apr 1;143(4):326-335. doi: 10.1001/jamaophthalmol.2025.0006.

Reference Type DERIVED
PMID: 40048197 (View on PubMed)

Stockwell AD, Chang MC, Mahajan A, Forrest W, Anegondi N, Pendergrass RK, Selvaraj S, Reeder J, Wei E, Iglesias VA, Creps NM, Macri L, Neeranjan AN, van der Brug MP, Scales SJ, McCarthy MI, Yaspan BL. Multi-ancestry GWAS analysis identifies two novel loci associated with diabetic eye disease and highlights APOL1 as a high risk locus in patients with diabetic macular edema. PLoS Genet. 2023 Aug 16;19(8):e1010609. doi: 10.1371/journal.pgen.1010609. eCollection 2023 Aug.

Reference Type DERIVED
PMID: 37585454 (View on PubMed)

Other Identifiers

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GR40550

Identifier Type: -

Identifier Source: org_study_id

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