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

NCT04503551 | Completed Phase 3 Results FDA Drug

• 1 other identifier: GR41675
• Study Type: interventional
• Target: 174
• Locations: 2 countries
• Sites: 65

Brief Summary

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

Conditions

Diabetic Retinopathy

Keywords

Port Delivery System; ranibizumab; Diabetic Retinopathy; anti-VEGF, nonproliferative diabetic retinopathy, retina, vision loss, retinal disease, eye disease

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With a ≥2-Step Improvement From Baseline on the Early Treatment Diabetic Retinopathy Study-Diabetic Retinopathy Severity Scale (ETDRS-DRSS) at Week 52

  ETDRS-DRSS classifies diabetic retinopathy (DR) into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy (PDR). DRSS grades= 10 (DR absent) - 85 (very advanced PDR), DRSS 90 = ungradable. All DRSS values are converted into a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR), allowing derivation of ≥2-step change from baseline for post-baseline assessment. A lower score represents less advanced diabetic retinopathy. The Cochran-Mantel Haenszel (CMH) method was used for analysis and weighted percentage of participants are estimated and reported in this outcome measure. Participants receiving supplemental treatments, prohibited therapy, or panretinal photocoagulation (PRP) were considered non-responders. Missing values not preceded by these intercurrent events were imputed using the last observation carried forward method. SD OCT= spectral-domain optical coherence tomography.

  Baseline, Week 52

Secondary Outcomes (34)

• Rate of Participants Developing a Vision-Threatening Complication or Center-involved Diabetic Macular Edema (CI-DME) Through Week 52

  From Baseline through Week 52

• Rate of Participants Developing PDR or ASNV Through Week 52

  From Baseline through Week 52

• Rate of Participants Developing CI-DME Through Week 52

  From Baseline through Week 52

• Rate of Participants Developing a ≥ 2-Step Worsening From Baseline on the ETDRS-DRSS Through Week 52

  From Baseline through Week 52

• Percentage of Participants With a ≥ 3-Step Improvement From Baseline on the ETDRS-DRSS at Week 52

  Week 52

Study Arms (2)

PDS Arm

EXPERIMENTAL

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

Drug: PDS Implant Pre-Filled with 100 mg/mL Ranibizumab; Drug: Intravitreal Ranibizumab 0.5 mg Injection

Comparator Arm

OTHER

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.

Drug: PDS Implant Pre-Filled with 100 mg/mL Ranibizumab; Drug: Intravitreal Ranibizumab 0.5 mg Injection

Interventions

Intravitreal Ranibizumab 0.5 mg Injection DRUG

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

Comparator Arm; PDS Arm

PDS Implant Pre-Filled with 100 mg/mL Ranibizumab DRUG

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

Comparator Arm; PDS Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (65)

Barnet Dulaney Perkins Eye Center

Mesa, Arizona, 85206, United States

Location

Retinal Consultants of Arizona;Opthalmology

Phoenix, Arizona, 85014, United States

Location

Associated Retina Consultants

Phoenix, Arizona, 85020, United States

Location

California Retina Consultants

Bakersfield, California, 93309, United States

Location

The Retina Partners

Encino, California, 91436, United States

Location

Retina Consultants of Orange County;Clinical Research

Fullerton, California, 92835, United States

Location

Jules Stein Eye Institute/ UCLA

Los Angeles, California, 90095, United States

Location

California Eye Specialists Medical Group

Pasadena, California, 91107, United States

Location

Kaiser Permanente;RESEARCH AND EVALUATION

Riverside, California, 92505, United States

Location

Retina Consultants Medical Group

Sacramento, California, 95841, United States

Location

Orange County Retina Medical Group

Santa Ana, California, 92705, United States

Location

Southwest Retina Research Center

Durango, Colorado, 81303, United States

Location

Colorado Clinical Research

Lakewood, Colorado, 80228, United States

Location

Retina Group of New England

Waterford, Connecticut, 06385, United States

Location

Retina Specialty Institute

Pensacola, Florida, 32503, United States

Location

Fort Lauderdale Eye Institute

Plantation, Florida, 33324, United States

Location

Retina Associates of Florida;Retina Associates of Florida

Tampa, Florida, 33609, United States

Location

Southeast Retina Center

Augusta, Georgia, 30909, United States

Location

Georgia Retina

Marietta, Georgia, 30060, United States

Location

Retina Consultants of Hawaii at Pali Momi Medical Center

‘Aiea, Hawaii, 96701, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Illinois Retina Associates

Joliet, Illinois, 60435, United States

Location

University Retina

Lemont, Illinois, 60439, United States

Location

Retina Associates

Lenexa, Kansas, 66215, United States

Location

Maine Eye Center

Portland, Maine, 04605, United States

Location

The Retina Care Center

Baltimore, Maryland, 21209, United States

Location

Johns Hopkins Hospital;Johns Hopkins Med;Wilmer Eye Inst

Baltimore, Maryland, 21287, United States

Location

Cumberland Valley Retina Consultants;Clinical Research

Hagerstown, Maryland, 21740, United States

Location

Associated Retinal Consultants - Royal Oak

Royal Oak, Michigan, 48073, United States

Location

VitreoRetinal Surgery PLLC;DBA Retina Consultants of Minnesota

Minneapolis, Minnesota, 55435, United States

Location

Pepose Vision Institute

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

Retina Associates of New Jersey

Teaneck, New Jersey, 07666, United States

Location

Retina Vitreous Surgeons of Central New York

Liverpool, New York, 13088, United States

Location

New York University (NYU)

New York, New York, 10012, United States

Location

Asheville Eye Associates Western Carolina Retinal Associates;Clinical Research

Asheville, North Carolina, 28803, United States

Location

Charlotte Eye Ear Nose and Throat Associates- SouthPark;Retina

Charlotte, North Carolina, 28210, United States

Location

Duke Eye Center

Durham, North Carolina, 27705, United States

Location

Cape Fear Retinal Associates

Wilmington, North Carolina, 28401, United States

Location

Ohio State Havener Eye Institute;Ophthalmology Research

Columbus, Ohio, 43212, United States

Location

Retina Vitreous Center - Glen Eagles

Edmond, Oklahoma, 73013, United States

Location

Retina Northwest;Research Department

Portland, Oregon, 97221, United States

Location

Mid Atlantic Retina;Retina Research

Philadelphia, Pennsylvania, 19107, United States

Location

Charleston Neuroscience

Ladson, South Carolina, 29456, United States

Location

Palmetto Retina Center

West Columbia, South Carolina, 29169, United States

Location

Charles Retina Institution;Retina surgery

Germantown, Tennessee, 38138, United States

Location

Southeastern Retina Associates

Knoxville, Tennessee, 37922, United States

Location

Tennessee Retina

Nashville, Tennessee, 37203, United States

Location

Retina Research Institute of Texas

Abilene, Texas, 79606, United States

Location

Austin Retina Associates;Opthalmology

Austin, Texas, 78705, United States

Location

Retina & Vitreous of Texas

Bellaire, Texas, 77401, United States

Location

Texas Retina Associates;Research

Dallas, Texas, 75231, United States

Location

Retina Center of Texas

Grapevine, Texas, 76051, United States

Location

Retina Consultants of Texas

Houston, Texas, 77401, United States

Location

Medical Center Ophthalmology Associates

San Antonio, Texas, 78240, United States

Location

Retina Consultants of Texas

The Woodlands, Texas, 77384, United States

Location

Rocky Mountain Retina Consultants

Murray, Utah, 84107, United States

Location

Retina Associates of Utah, PLLC;Clinical Research

Salt Lake City, Utah, 84107, United States

Location

Piedmont Eye Center

Lynchburg, Virginia, 24502, United States

Location

Wagner Kapoor Institute;Opthalmology

Norfolk, Virginia, 23502, United States

Location

Retina Institute of Virginia

Richmond, Virginia, 23235, United States

Location

Pacific Northwest Retina

Silverdale, Washington, 98383, United States

Location

Spokane Eye Clinical Research;Spokane Eye Surgery Center

Spokane, Washington, 99204, United States

Location

Emanuelli Research & Development Center

Arecibo, 612, Puerto Rico

Location

Related Publications (1)

• 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.

  PMID: 40048178 DERIVED

MeSH Terms

Conditions

Diabetic Retinopathy; Vision Disorders; Retinal Diseases; Eye Diseases

Interventions

Ranibizumab; Injections

Condition Hierarchy (Ancestors)

Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Drug Administration Routes; Drug Therapy; Therapeutics

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

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
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2020
• First Posted: August 7, 2020
• Study Start: August 10, 2020
• Primary Completion: October 3, 2022
• Study Completion: February 23, 2026
• Last Updated: April 2, 2026
• Results First Posted: November 25, 2025

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

PR (1); US (64)