This Study Will Evaluate the Efficacy, Safety, and Pharmacokinetics of the Port Delivery System With Ranibizumab in Participants With Diabetic Macular Edema Compared With Intravitreal Ranibizumab (Pagoda)

A Phase III, Multicenter, Randomized, Visual Assessor-Masked, Active-comparator Study of the Efficacy, Safety, and Pharmacokinetics of the Port Delivery System With Ranibizumab in Patients With Diabetic Macular Edema (Pagoda)

This study will evaluate the efficacy, safety, and pharmacokinetics of the Port Delivery System with Ranibizumab (PDS) in Participants with Diabetic Macular Edema (DME) when treated every 24 weeks (Q24W) compared with intravitreal ranibizumab 0.5 mg every 4 weeks (Q4W).

Study Overview

• Status: Active, not recruiting
• Conditions: Diabetic Macular Edema
• Intervention / Treatment: Drug: PDS Implant Pre-Filled with 100 mg/mL Ranibizumab; Drug: Intravitreal Ranibizumab 0.5 mg Injection

• Study Type: Interventional
• Enrollment (Actual): 634
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Mesa, Arizona, United States, 85206
      • Barnet Dulaney Perkins Eye Center
    • Phoenix, Arizona, United States, 85020
      • Associated Retina Consultants
    • Phoenix, Arizona, United States, 85053
      • Retinal Consultants of Arizona
    • Phoenix, Arizona, United States, 85016
      • Arizona Retina and Vitreous Consultants
  • California
    • Bakersfield, California, United States, 93309
      • California Retina Consultants
    • Beverly Hills, California, United States, 90211
      • Retina-Vitreous Associates Medical Group
    • Encino, California, United States, 91436
      • The Retina Partners
    • Fullerton, California, United States, 92835-3424
      • Retina Consultants of Orange County
    • Mountain View, California, United States, 94040
      • N CA Retina Vitreous Assoc
    • Oakland, California, United States, 94609
      • East Bay Retina Consultants
    • Pasadena, California, United States, 91107
      • California Eye Specialists Medical group Inc.
    • Pasadena, California, United States, 91105
      • Doheny Eye Institute
    • Sacramento, California, United States, 95825
      • Retinal Consultants Med Group
    • San Francisco, California, United States, 94110
      • Zuckerberg San Francisco General Hospital
    • Santa Ana, California, United States, 92705
      • Orange County Retina Med Group
    • Santa Barbara, California, United States, 93103
      • California Retina Consultants
  • Colorado
    • Fort Collins, Colorado, United States, 80528
      • Eye Center of Northern CO
    • Lakewood, Colorado, United States, 80228
      • Colorado Retina Associates, PC
  • Connecticut
    • Waterford, Connecticut, United States, 06385
      • Retina Group of New England
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Retina Group of Florida
    • Fort Myers, Florida, United States, 33912
      • National Ophthalmic Research Institute
    • Pensacola, Florida, United States, 32503
      • Retina Specialty Institute
    • Plantation, Florida, United States, 33324
      • Fort Lauderdale Eye Institute
    • Saint Petersburg, Florida, United States, 33711
      • Retina Vitreous Assoc of FL
    • Tallahassee, Florida, United States, 32308
      • Southern Vitreoretinal Assoc
    • Tampa, Florida, United States, 33609
      • Retina Associates of Florida, LLC
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Southeast Retina Center
    • Marietta, Georgia, United States, 30060-1137
      • Georgia Retina PC
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Medical Group/Northwestern University
    • Joliet, Illinois, United States, 60435
      • Illinois Retina Associates
    • Oak Forest, Illinois, United States, 60452
      • University Retina and Macula Associates, PC
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Wolfe Eye Clinic
  • Kansas
    • Lenexa, Kansas, United States, 66215
      • Retina Associates
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Retina Associates of Kentucky
  • Maine
    • Portland, Maine, United States, 04101
      • Maine Eye Center
  • Maryland
    • Baltimore, Maryland, United States, 21209
      • The Retina Care Center
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Med; Wilmer Eye Inst
    • Chevy Chase, Maryland, United States, 20815
      • Retina Group of Washington
    • Hagerstown, Maryland, United States, 21740
      • Cumberland Valley Retina Associates
    • Towson, Maryland, United States, 21204
      • Retina Specialists
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Boston, Massachusetts, United States, 02114
      • Ophthalmic Consultants of Boston
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Foundation for Vision Research
    • Grand Rapids, Michigan, United States, 49546
      • Associated Retinal Consultants
  • Minnesota
    • Minneapolis, Minnesota, United States, 55435
      • Vitreo Retinal Surgery
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • Midwest Vision Research Foundation
    • Saint Louis, Missouri, United States, 63128
      • The Retina Institute
  • Nevada
    • Reno, Nevada, United States, 89502
      • Sierra Eye Associates
  • New Jersey
    • Bloomfield, New Jersey, United States, 07003
      • Envision Ocular, LLC
    • Cherry Hill, New Jersey, United States, 08034
      • Mid Atlantic Retina
    • Teaneck, New Jersey, United States, 07666
      • Retina Associates of NJ
  • New York
    • Hauppauge, New York, United States, 11788
      • Long Is. Vitreoretinal Consult
    • Liverpool, New York, United States, 13088
      • Retina Vit Surgeons/Central NY
    • New York, New York, United States, 10017
      • New York University
    • Oceanside, New York, United States, 11572
      • Ophthalmic Cons of Long Island
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Western Carolina Retinal Associate PA
    • Charlotte, North Carolina, United States, 28210
      • Char Eye Ear &Throat Assoc
    • Durham, North Carolina, United States, 27705
      • Duke Eye Center
    • Hickory, North Carolina, United States, 28602
      • Graystone Eye
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Cincinnati Eye Institute
    • Cleveland, Ohio, United States, 44195-0001
      • Cleveland Clinic Foundation; Cole Eye Institute
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
    • Dublin, Ohio, United States, 43016
      • Midwest Retina
  • Oklahoma
    • Edmond, Oklahoma, United States, 73013
      • Retina Vitreous Center
  • Oregon
    • Portland, Oregon, United States, 97221
      • Retina Northwest
  • Pennsylvania
    • Chambersburg, Pennsylvania, United States, 17201
      • Cumberland Valley Retina Consultants; Chambersburg
  • South Carolina
    • Ladson, South Carolina, United States, 29456
      • Charleston Neuroscience Inst
    • Mount Pleasant, South Carolina, United States, 29464
      • Carolina Eyecare Physicians
    • West Columbia, South Carolina, United States, 29169
      • Palmetto Retina Center, LLC
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Charles Retina Institute
    • Nashville, Tennessee, United States, 37203
      • Tennessee Retina PC
  • Texas
    • Abilene, Texas, United States, 79606
      • Retina Res Institute of Texas
    • Arlington, Texas, United States, 76012
      • Texas Retina Associates
    • Austin, Texas, United States, 78750
      • Austin Clinical Research LLC
    • Austin, Texas, United States, 78705-1169
      • Austin Retina Associates
    • Austin, Texas, United States, 78705
      • Austin Research Center for Retina
    • Bellaire, Texas, United States, 77401-3510
      • Retina & Vitreous of Texas
    • Dallas, Texas, United States, 75231
      • Texas Retina Associates
    • Fort Worth, Texas, United States, 76104
      • Texas Retina Associates
    • San Antonio, Texas, United States, 78240
      • Med Center Ophthalmology Assoc
    • The Woodlands, Texas, United States, 77384-4167
      • Retina Consultants of Texas
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Rocky Mountain Retina
    • Salt Lake City, Utah, United States, 84107
      • Retina Associates of Utah, PLLC
  • Virginia
    • Lynchburg, Virginia, United States, 24502
      • Piedmont Eye Center
    • Norfolk, Virginia, United States, 23502
      • Wagner Kapoor Institute
    • Richmond, Virginia, United States, 23235
      • Retina Institute of Virginia
  • Washington
    • Silverdale, Washington, United States, 98383
      • Retina Center Northwest
    • Spokane, Washington, United States, 99204
      • Spokane Eye Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 ≤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 um on SD-OCT at screening
• BCVA score of 78 to 25 letters (20/32 to 20/320 approximate Snellen equivalent)

Exclusion Criteria:

• High-risk proliferative diabetic retinopathy
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PDS Arm; Participants randomized to the PDS arm will receive intravitreal ranibizumab injection every 4 weeks (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 every 24-weeks (Q24W) thereafter	Drug: PDS Implant Pre-Filled with 100 mg/mL Ranibizumab; Will be administered as per the schedule described in individual arm.
Active Comparator: Intravitreal Arm; Participants randomized to the intravitreal arm will receive intravitreal ranibizumab injection every 4 weeks 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; Will be administered as per the schedule described in individual arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	ETDRS-DRSS = ETDRS Diabetic Retinopathy Severity Scale	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
Percentage of participants who lose <15, <10, and <5 letters in BCVA from baseline over time		Baseline up to Week 120
Percentage of participants who gain ≥15, ≥10, ≥5, ≥0 letters in BCVA from baseline over time		Baseline up to Week 120
Percentage of participants with a BCVA Snellen equivalent of 20/40 or better over time		Baseline up to Week 120
Percentage of participants with a BCVA Snellen equivalent of 20/200 or worse over time		Baseline up to Week 120
Percentage of participants with a ≥2-step improvement from baseline on the ETDRS-DRSS over time		Baseline up to Week 120
Percentage of participants with a ≥3-step improvement from baseline on the ETDRS-DRSS over time		Baseline up to Week 120
Time to ≥2-step worsening from baseline on the ETDRS-DRSS		Baseline up to Week 120
Time to ≥3-step worsening from baseline on the ETDRS-DRSS		Baseline up to Week 120
Change from baseline in ETDRS-DRSS score over time		Baseline up to Week 120
Change from baseline in CST as measured on SD-OCT over time		Baseline up to Week 120
Change from baseline in total macular volume as measured on SD-OCT over time		Baseline up to Week 120
Percentage of participants with absence of intraretinal fluid over time (intraretinal fluid as measured in the central 1 mm subfield)		Baseline up to Week 120
Percentage of participants with absence of subretinal fluid over time (subretinal fluid as measured in the central 1 mm subfield)		Baseline up to Week 120
Percentage of participants with absence of intraretinal fluid and subretinal fluid over time		Baseline up to Week 120
Percentage of participants with absence DME (defined as CST ≥325 μm on SD-OCT) over time	DME = diabetic macular edema	Baseline up to Week 120
Time to PDR (defined as a score ≥60 on the ETDRS-DRSS)	PDR = proliferative diabetic retinopathy	Baseline up to Week 120
Percentage of participants who do not undergo supplemental treatment with intravitreal ranibizumab within each refill-exchange interval		Baseline up to Week 120
Percentage of participants who report preferring PDS treatment compared with intravitreal ranibizumab treatment	As measured by the PDS Patient Preference Questionnaire at Week 64 among patients in the PDS arm efficacy population, mITT population	Baseline to Week 64
Percentage of participants who report preferring PDS treatment compared with intravitreal ranibizumab treatment, as measured by the PDS Patient Preference Questionnaire (PPPQ) at Week 64	Participants in in a subset of patients with bilateral disease who are simultaneously receiving ranibizumab via study eye PDS implant and fellow eye intravitreal injection	Baseline to Week 64
Patient-reported vision-related functioning and health-related quality of life (HRQoL) among patients in both treatment arms, as measured by changes from baseline	As measured by in the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) composite score and Near Activities, Distance Activities, and Driving subscale scores	, Baseline Week 48, Week 96
Patient-reported vision-related functioning and HRQoL, as measured by the proportion of patients with a ≥ 4-point improvement from baseline in the NEI VFQ-25 composite score at Weeks 48 and 96 among patients in both treatment arms		Baseline, Week 48, Week 96
Incidence and severity of ocular adverse events		Baseline to Week 120
Incidence and severity of non-ocular adverse events		Baseline up to Week 120
Incidence, severity, and duration of adverse events of special interest		Baseline up to Week 120
Serum concentration of ranibizumab observed over time		Baseline up to Week 120
PK parameter value area under the concentration- time curve over 24 weeks (AUC24W)		Baseline to Week 24
Pharmacokinetic (PK) parameter maximum serum concentration (Cmax)		Baseline up to Week 120
PK Parameter minimum serum concentration (Cmin)		Baseline up to Week 120
Time of maximum observed serum concentration (Tmax) after PDS implant insertion		Baseline up to Week 120
Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs during the study		Baseline up to Week 120
Prevalence of neutralizing antibodies at baseline and incidence of neutralizing antibodies during the study		Baseline up to Week 120
Reported incidence of device deficiencies		Baseline up to Week 120
Incidence and severity of ocular adverse events		Baseline up to Week 120
Incidence, severity, and duration of ocular adverse events of special interest during the postoperative period (up to 37 days after initial implantation) and follow-up period (> 37 days after implantation surgery)		Baseline up to Week 120
Incidence and severity of adverse device effects		Baseline up to Week 120
Incidence, causality, severity, and duration of anticipated serious adverse device effects		Baseline up to Week 120

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2019
• Primary Completion (Actual): September 19, 2022
• Study Completion (Estimated): February 28, 2025

Study Registration Dates

• First Submitted: September 26, 2019
• First Submitted That Met QC Criteria: September 26, 2019
• First Posted (Actual): September 30, 2019

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Port Delivery System
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Macular Edema; Edema; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab
• Other Study ID Numbers: GR40550

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No