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

NCT04108156 | Active Not Recruiting Phase 3 FDA Drug

• 1 other identifier: GR40550
• Study Type: interventional
• Target: 672
• Locations: 1 country
• Sites: 88

Brief Summary

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.

Conditions

Diabetic Macular Edema

Keywords

Port Delivery System

Outcome Measures

Primary Outcomes (12)

• Change in BCVA Score From Baseline Averaged Over Weeks 60 and 64 as Measured Using the ETDRS Chart in the Efficacy Population Using a Treatment Policy Strategy for all Intercurrent Events

  BCVA = Best-Corrected Visual Acuity ETDRS = Early Treatment Diabetic Retinopathy Study A vision score of 20/20 vision is considered normal. A score of 20/200 is considered being legally blind.

  Baseline to Week 64

• Substudy: Number of Participants With Ocular and Systemic (Non-ocular) Adverse Events (AEs) and Severity of Ocular and Systemic AEs

  Baseline to Week 72

• Substudy: Number of Participants With Adverse Events of Special Interests (AESIs) and Severity of AESIs

  Baseline to Week 72

• Substudy: Duration of AESIs

  Baseline to Week 72

• Substudy: Number of Participants With Ocular AESIs and Severity of Ocular AESIs During the Post-operative Period

  Up to Day 37 post re-implantation

• Substudy: Number of Participants With Ocular AESIs and Severity of Ocular AESIs During the Follow-up Period

  > 37 days post-implantation (up to approximately 72 weeks)

• Substudy: Duration of Ocular AESIs During the Post-operative Period

  Up to Day 37 post re-implantation

• Substudy: Duration of Ocular AESIs During the Follow-up Period

  > 37 days post-implantation (up to approximately 72 weeks)

• Substudy: Number of Participants With Adverse Device Effects (ADEs) and Severity of ADEs

  Baseline to Week 72

• Substudy: Number of Participants With Anticipated Serious ADEs

  Baseline to Week 72

• Substudy: Duration of Serious ADEs

  Baseline to Week 72

• Substudy: Number of Device Deficiencies

  Baseline to Week 72

Secondary Outcomes (48)

• Change in BCVA Score From Baseline Averaged Over Weeks 60 and 64 as Measured With Use of the ETDRS Chart in the Modified Intent-to-treat (mITT) Population Using a Treatment Policy Strategy for All Intercurrent Events

  Baseline to Week 64

• Change in BCVA Score From Baseline Averaged Over Weeks 60 and 64 as Measured With Use of the ETDRS Chart in the mITT Population Using a Hypothetical Strategy for All Intercurrent Events

  Baseline to Week 64

• Percentage of Participants With a ≥2-step Improvement From Baseline on the ETDRS-DRSS at Week 64 in the Efficacy Population

  Baseline to Week 64

• Percentage of Participants With a ≥2-step Improvement From Baseline on the ETDRS-DRSS at Week 64 in the mITT population

  Baseline to Week 64

• Change from Baseline in BCVA as Measured on the ETDRS Chart Over Time

  Baseline up to Week 120

Study Arms (5)

PDS Arm

EXPERIMENTAL

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.

Drug: PDS Implant Pre-Filled with 100 mg/mL Ranibizumab; Drug: Ranibizumab refill exchange

Intravitreal Arm

ACTIVE COMPARATOR

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.

Drug: Intravitreal Ranibizumab 0.5 mg Injection; Drug: Ranibizumab refill exchange

Substudy: Cohort 1

EXPERIMENTAL

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.

Drug: PDS Implant Pre-Filled with 100 mg/mL Ranibizumab; Drug: Ranibizumab refill exchange

Substudy: Cohort 2a

EXPERIMENTAL

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.

Drug: Ranibizumab refill exchange

Substudy: Cohort 2b

EXPERIMENTAL

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.

Drug: Ranibizumab refill exchange

Interventions

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

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

PDS Arm; Substudy: Cohort 1

Intravitreal Ranibizumab 0.5 mg Injection DRUG

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

Intravitreal Arm

Ranibizumab refill exchange DRUG

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

Intravitreal Arm; PDS Arm; Substudy: Cohort 1; Substudy: Cohort 2a; Substudy: Cohort 2b

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 (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)

You may not qualify if:

• 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:
• 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
• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (88)

Barnet Dulaney Perkins Eye Center

Mesa, Arizona, 85206, United States

Location

Retinal Consultants of Arizona;Opthalmology

Phoenix, Arizona, 85014, United States

Location

Arizona Retina and Vitreous Consultants

Phoenix, Arizona, 85016, United States

Location

Associated Retina Consultants

Phoenix, Arizona, 85020, 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

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

Northern California Retina-Vitreous Associates

Mountain View, California, 94040, United States

Location

East Bay Retina Consultants

Oakland, California, 94609, United States

Location

Doheny Eye Institute

Pasadena, California, 91105, United States

Location

California Eye Specialists Medical Group

Pasadena, California, 91107, United States

Location

Retina Consultants Medical Group

Sacramento, California, 95841, United States

Location

Zuckerberg San Francisco General Hospital and Trauma Center

San Francisco, California, 94110, United States

Location

Orange County Retina Medical Group

Santa Ana, California, 92705, United States

Location

California Retina Consultants;Research Department

Santa Barbara, California, 93103, United States

Location

Eye Center of Northern Colorado

Fort Collins, Colorado, 80528, United States

Location

Colorado Clinical Research

Lakewood, Colorado, 80228, United States

Location

Retina Group of New England

Waterford, Connecticut, 06385, United States

Location

Retina Group of Florida

Fort Lauderdale, Florida, 33308, United States

Location

National Ophthalmic Research Institute

Fort Myers, Florida, 33912, United States

Location

Retina Specialty Institute

Pensacola, Florida, 32503, United States

Location

Fort Lauderdale Eye Institute

Plantation, Florida, 33324, United States

Location

Retina Vitreous Associates of Florida

St. Petersburg, Florida, 33711, United States

Location

Southern Vitreoretinal Associates;Research

Tallahassee, Florida, 32308, 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

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

Wolfe Eye Clinic

West Des Moines, Iowa, 50266, United States

Location

Retina Associates

Lenexa, Kansas, 66215, United States

Location

Retina & Vitreous Associates of Kentucky

Lexington, Kentucky, 40509, United States

Location

Maine Eye Center

Portland, Maine, 04605, United States

Location

Johns Hopkins Hospital;Johns Hopkins Med;Wilmer Eye Inst

Baltimore, Maryland, 21287, United States

Location

The Retina Group of Washington;Retinal Disease

Chevy Chase, Maryland, 20815, United States

Location

Cumberland Valley Retina Consultants;Clinical Research

Hagerstown, Maryland, 21740, United States

Location

Retina Specialist

Towson, Maryland, 21204, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Ophthalmic Consultants of Boston

Boston, Massachusetts, 02114, United States

Location

Vitreo Retinal Associates

Worcester, Massachusetts, 01605, United States

Location

Retina Specialists Of Michigan

Grand Rapids, Michigan, 49546, 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

Retina Institute

St Louis, Missouri, 63128, 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

Long Island Vitreoretinal Consultants;Opthalmology

Great Neck, New York, 11021, 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, 10017, United States

Location

Ophthalmic Consultants of Long Island

Oceanside, New York, 11572, 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

Graystone Eye;Clinical Research

Hickory, North Carolina, 28602, United States

Location

Cincinnati Eye Institute;Retina

Cincinnati, Ohio, 45242, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ohio State Havener Eye Institute;Ophthalmology Research

Columbus, Ohio, 43212, United States

Location

Midwest Retina;Retina/Vitreous

Dublin, Ohio, 43016, 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

Philadelphia, Pennsylvania, 19107, United States

Location

Charleston Neuroscience

Ladson, South Carolina, 29456, United States

Location

Carolina Eyecare Physicians

Mt. Pleasant, South Carolina, 29464, 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

Tennessee Retina

Nashville, Tennessee, 37203, United States

Location

Retina Research Institute of Texas

Abilene, Texas, 79606, United States

Location

Texas Retina Associates

Arlington, Texas, 76012, United States

Location

Austin Research Center for Retina

Austin, Texas, 78705, United States

Location

Austin Retina Associates;Opthalmology

Austin, Texas, 78705, United States

Location

Austin Clinical Research, LLC

Austin, Texas, 78750, United States

Location

Retina & Vitreous of Texas

Bellaire, Texas, 77401, United States

Location

Texas Retina Associates;Research

Dallas, Texas, 75231, United States

Location

Texas Retina Associates

Fort Worth, Texas, 76104, United States

Location

Retina Consultants of Texas

Houston, Texas, 77401, United States

Location

Medical Center Ophthalmology Associates

San Antonio, Texas, 78240, 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

Related Publications (2)

• 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.

  PMID: 40048197 DERIVED

• 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.

  PMID: 37585454 DERIVED

MeSH Terms

Interventions

Ranibizumab; Injections

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

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The substudy is a non-randomized, open-label study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2019
• First Posted: September 30, 2019
• Study Start: September 30, 2019
• Primary Completion (Estimated): July 20, 2027
• Study Completion (Estimated): July 20, 2027
• Last Updated: July 10, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share

Locations

US (88)