A Multicenter, Randomized Study in Participants With Diabetic Retinopathy Without Center-involved Diabetic Macular Edema To Evaluate the Efficacy, Safety, and Pharmacokinetics of Ranibizumab Delivered Via the Port Delivery System Relative to the Comparator Arm

NCT ID: NCT04503551

Last Updated: 2025-11-25

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

174 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-08-10

Study Completion Date

2026-01-31

Brief Summary

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Study GR41675 is a Multicenter, Randomized Study in Participants with Diabetic Retinopathy (DR) Without Center-Involved Diabetic Macular Edema (CI-DME) to Evaluate the Efficacy, Safety of the Port Delivery System with Ranibizumab (PDS) Relative to the Comparator Arm

Detailed Description

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Conditions

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Diabetic Retinopathy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
The visual acuity examiner will only conduct refraction and visual acuity assessments and will be masked, as best as possible, to the following items: study eye assignment; study visit type; and treatment assignment.

Study Groups

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PDS Arm

Participants randomized to the PDS arm will receive two intravitreal ranibizumab injections 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 every 36-weeks (Q36W) 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.

Intravitreal Ranibizumab 0.5 mg Injection

Intervention Type DRUG

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

Comparator Arm

Participants randomized to the comparator arm will undergo study visits every 4 weeks (Q4W) for comprehensive clinical monitoring until they receive the PDS implant (pre-filled with ranibizumab). PDS implant refill-exchange procedures will be performed on a fixed interval Q36W thereafter. Participants will be eligible to receive intravitreal ranibizumab 0.5 mg injections if treatment eligibility criteria are met.

Group Type OTHER

PDS Implant Pre-Filled with 100 mg/mL Ranibizumab

Intervention Type DRUG

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

Intravitreal Ranibizumab 0.5 mg Injection

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

Eligibility Criteria

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Inclusion Criteria

* Age ≥18 years at time of signing Informed Consent Form
* Documented diagnosis of diabetes mellitus (Type 1 or Type 2)
* HbA1c level of ≤12% within 2 months prior to screening or at screening


* Moderately severe or severe NPDR (ETDRS-DRSS level 47 or 53)
* BCVA score of ≥ 69 letters (20/40 approximate Snellen equivalent or better)

Exclusion Criteria

* Uncontrolled blood pressure
* Cerebrovascular accident or myocardial infarction within 6 months prior to randomization
* Atrial fibrillation diagnosis or worsening within 6 months prior to randomization
* Current systemic treatment for a confirmed active systemic infection
* Renal failure requiring renal transplant, hemodialysis, or peritoneal dialysis, or anticipated to require hemodialysis or peritoneal dialysis at any time during the study
* History 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 patient at high risk for treatment complications in the opinion of the investigator or Sponsor


* Presence of center-involved diabetic macular edema (defined as CST ≥325 µm)
* Any intravitreal anti-VEGF treatment at any time prior to randomization
* Any use of medicated intraocular implants, including Ozurdex® or Iluvien® implants at any time prior to randomization
* Any intravitreal corticosteroid treatment at any time prior to randomization
* Any periocular (e.g., subtenon) corticosteroid treatment at any time prior to randomization
* Any PRP at any time prior to randomization
* Any macular laser photocoagulation (such as micropulse and focal or grid laser) at any time prior to randomization
* Active intraocular inflammation (grade trace or above)
* Clinically significant abnormalities of the vitreous-retinal interface involving the macular area or disrupting the macular architecture, such as vitreous-retinal traction or epiretinal membrane (assessed by the investigator and confirmed by the central reading center)
* Uncontrolled ocular hypertension or glaucoma and any such condition the investigator determines may require a glaucoma-filtering surgery during a participant's participation in the study
* History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery
* Any concurrent ocular condition (e.g., cataract, epiretinal membrane) that would require surgical intervention during the study to prevent or treat visual loss that might result from that condition
* Any concurrent ocular condition (e.g., amblyopia, strabismus) that may affect interpretation of study results
* History of other ocular diseases that gives reasonable suspicion of a disease or condition that contraindicates the use of ranibizumab, that might affect interpretation of study results, or that renders the participant at high risk for treatment complications


* Suspected or active ocular or periocular infection of either eye
* Any history uveitis including idiopathic, drug-associated or autoimmune-associated uveitis
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

Retinal Consultants of Arizona;Opthalmology

Phoenix, Arizona, United States

Site Status

Associated Retina Consultants

Phoenix, Arizona, United States

Site Status

California Retina Consultants

Bakersfield, California, United States

Site Status

The Retina Partners

Encino, California, United States

Site Status

Retina Consultants of Orange County;Clinical Research

Fullerton, California, United States

Site Status

Jules Stein Eye Institute/ UCLA

Los Angeles, California, United States

Site Status

California Eye Specialists Medical Group

Pasadena, California, United States

Site Status

Kaiser Permanente;RESEARCH AND EVALUATION

Riverside, California, United States

Site Status

Retina Consultants Medical Group

Sacramento, California, United States

Site Status

Orange County Retina Medical Group

Santa Ana, California, United States

Site Status

Southwest Retina Research Center

Durango, Colorado, United States

Site Status

Colorado Clinical Research

Lakewood, Colorado, United States

Site Status

Retina Group of New England

Waterford, Connecticut, United States

Site Status

Retina Specialty Institute

Pensacola, Florida, United States

Site Status

Fort Lauderdale Eye Institute

Plantation, Florida, United States

Site Status

Retina Associates of Florida;Retina Associates of Florida

Tampa, Florida, United States

Site Status

Southeast Retina Center

Augusta, Georgia, United States

Site Status

Georgia Retina

Marietta, Georgia, United States

Site Status

Retina Consultants of Hawaii at Pali Momi Medical Center

‘Aiea, Hawaii, United States

Site Status

Northwestern Memorial Hospital

Chicago, Illinois, United States

Site Status

Illinois Retina Associates

Joliet, Illinois, United States

Site Status

University Retina

Lemont, Illinois, United States

Site Status

Retina Associates

Lenexa, Kansas, 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 Hospital;Johns Hopkins Med;Wilmer Eye Inst

Baltimore, Maryland, United States

Site Status

Cumberland Valley Retina Consultants;Clinical Research

Hagerstown, Maryland, United States

Site Status

Associated Retinal Consultants - Royal Oak

Royal Oak, Michigan, United States

Site Status

VitreoRetinal Surgery PLLC;DBA Retina Consultants of Minnesota

Minneapolis, Minnesota, United States

Site Status

Pepose Vision Institute

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

Retina Associates of New Jersey

Teaneck, New Jersey, United States

Site Status

Retina Vitreous Surgeons of Central New York

Liverpool, New York, United States

Site Status

New York University (NYU)

New York, New York, United States

Site Status

Asheville Eye Associates Western Carolina Retinal Associates;Clinical Research

Asheville, North Carolina, United States

Site Status

Charlotte Eye Ear Nose and Throat Associates- SouthPark;Retina

Charlotte, North Carolina, United States

Site Status

Duke Eye Center

Durham, North Carolina, United States

Site Status

Cape Fear Retinal Associates

Wilmington, North Carolina, United States

Site Status

Ohio State Havener Eye Institute;Ophthalmology Research

Columbus, Ohio, United States

Site Status

Retina Vitreous Center - Glen Eagles

Edmond, Oklahoma, United States

Site Status

Retina Northwest;Research Department

Portland, Oregon, United States

Site Status

Mid Atlantic Retina;Retina Research

Philadelphia, Pennsylvania, United States

Site Status

Charleston Neuroscience

Ladson, South Carolina, United States

Site Status

Palmetto Retina Center

West Columbia, South Carolina, United States

Site Status

Charles Retina Institution;Retina surgery

Germantown, Tennessee, United States

Site Status

Southeastern Retina Associates

Knoxville, Tennessee, United States

Site Status

Tennessee Retina

Nashville, Tennessee, United States

Site Status

Retina Research Institute of Texas

Abilene, Texas, United States

Site Status

Austin Retina Associates;Opthalmology

Austin, Texas, United States

Site Status

Retina & Vitreous of Texas

Bellaire, Texas, United States

Site Status

Texas Retina Associates;Research

Dallas, Texas, United States

Site Status

Retina Center of Texas

Grapevine, Texas, United States

Site Status

Retina Consultants of Texas

Houston, Texas, United States

Site Status

Medical Center Ophthalmology Associates

San Antonio, Texas, United States

Site Status

Rocky Mountain Retina Consultants

Murray, Utah, United States

Site Status

Retina Associates of Utah, PLLC;Clinical Research

Salt Lake City, Utah, United States

Site Status

Piedmont Eye Center

Lynchburg, Virginia, United States

Site Status

Wagner Kapoor Institute;Opthalmology

Norfolk, Virginia, United States

Site Status

Retina Institute of Virginia

Richmond, Virginia, United States

Site Status

Pacific Northwest Retina

Silverdale, Washington, United States

Site Status

Spokane Eye Clinical Research;Spokane Eye Surgery Center

Spokane, Washington, United States

Site Status

Emanuelli Research & Development Center

Arecibo, , Puerto Rico

Site Status

Countries

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United States Puerto Rico

References

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Pieramici DJ, Awh CC, Chang M, Emanuelli A, Holekamp NM, Hu AY, Suner IJ, Wykoff CC, Brittain C, Howard D, Quezada-Ruiz C, Santhanakrishnan A, Latkany P. Port Delivery System With Ranibizumab vs Monitoring in Nonproliferative Diabetic Retinopathy Without Macular Edema: The Pavilion Randomized Clinical Trial. JAMA Ophthalmol. 2025 Apr 1;143(4):317-325. doi: 10.1001/jamaophthalmol.2025.0001.

Reference Type DERIVED
PMID: 40048178 (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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GR41675

Identifier Type: -

Identifier Source: org_study_id

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