Diabetic Macular EdemaPhase 3PagodaNCT04108156
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
A Phase 3 study testing PDS Implant Pre-Filled with 100 mg/mL Ranibizumab, Intravitreal Ranibizumab 0.5 mg Injection and Ranibizumab refill exchange in people with Diabetic Macular Edema, run by Hoffmann-La Roche at 89 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Macular Edema
- What is being tested?
- PDS Implant Pre-Filled with 100 mg/mL Ranibizumab, Intravitreal Ranibizumab 0.5 mg Injection and Ranibizumab refill exchange
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 672 participants
- Where
- 89 sitesUnited States
- Study dates
- 30 Sep 2019to 20 Jul 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 24Show fewer
- 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
- Ocular Exclusion Criteria for Study Eye:
- 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
- Ongoing ocular complications that might affect participant safety Ocular Exclusion Criteria for Either Eye
- Suspected or active ocular or periocular infection (e.g., infectious conjunctivitis or endophthalmitis)
- Any history of uveitis
- Active blepharitis
Trial locations and contacts
89 sites in 1 country.
89 sites in 1 country
United States89 sites
Retina Research Institute of Texas
Abilene, Texas, 79606
Texas Retina Associates
Arlington, Texas, 76012
Asheville Eye Associates Western Carolina Retinal Associates;Clinical Research
Asheville, North Carolina, 28803
Southeast Retina Center
Augusta, Georgia, 30909
Austin Research Center for Retina
Austin, Texas, 78705
Austin Retina Associates;Opthalmology
Austin, Texas, 78705
Austin Clinical Research, LLC
Austin, Texas, 78750
California Retina Consultants
Bakersfield, California, 93309
The Retina Care Center
Baltimore, Maryland, 21209
Johns Hopkins Hospital;Johns Hopkins Med;Wilmer Eye Inst
Baltimore, Maryland, 21287
Retina & Vitreous of Texas
Bellaire, Texas, 77401
Retina-Vitreous Associates Medical Group
Beverly Hills, California, 90211
Envision Ocular, LLC
Bloomfield, New Jersey, 07003
Tufts Medical Center
Boston, Massachusetts, 02111
Ophthalmic Consultants of Boston
Boston, Massachusetts, 02114
Charlotte Eye Ear Nose and Throat Associates- SouthPark;Retina
Charlotte, North Carolina, 28210
Pepose Vision Institute
Chesterfield, Missouri, 63017
The Retina Group of Washington;Retinal Disease
Chevy Chase, Maryland, 20815
Northwestern Memorial Hospital
Chicago, Illinois, 60611
Cincinnati Eye Institute;Retina
Cincinnati, Ohio, 45242
Cleveland Clinic
Cleveland, Ohio, 44195
Ohio State Havener Eye Institute;Ophthalmology Research
Columbus, Ohio, 43212
Texas Retina Associates;Research
Dallas, Texas, 75231
Midwest Retina;Retina/Vitreous
Dublin, Ohio, 43016
Duke Eye Center
Durham, North Carolina, 27705
Retina Vitreous Center - Glen Eagles
Edmond, Oklahoma, 73013
The Retina Partners
Encino, California, 91436
Eye Center of Northern Colorado
Fort Collins, Colorado, 80528
Retina Group of Florida
Fort Lauderdale, Florida, 33308
National Ophthalmic Research Institute
Fort Myers, Florida, 33912
Texas Retina Associates
Fort Worth, Texas, 76104
Retina Consultants of Orange County;Clinical Research
Fullerton, California, 92835
Charles Retina Institution;Retina surgery
Germantown, Tennessee, 38138
Retina Specialists Of Michigan
Grand Rapids, Michigan, 49546
Long Island Vitreoretinal Consultants;Opthalmology
Great Neck, New York, 11021
Cumberland Valley Retina Consultants;Clinical Research
Hagerstown, Maryland, 21740
Graystone Eye;Clinical Research
Hickory, North Carolina, 28602
Retina Consultants of Texas
Houston, Texas, 77401
Illinois Retina Associates
Joliet, Illinois, 60435
Charleston Neuroscience
Ladson, South Carolina, 29456
Colorado Clinical Research
Lakewood, Colorado, 80228
University Retina
Lemont, Illinois, 60439
Retina Associates
Lenexa, Kansas, 66215
Retina & Vitreous Associates of Kentucky
Lexington, Kentucky, 40509
Retina Vitreous Surgeons of Central New York
Liverpool, New York, 13088
Jules Stein Eye Institute/ UCLA
Los Angeles, California, 90095
Piedmont Eye Center
Lynchburg, Virginia, 24502
Georgia Retina
Marietta, Georgia, 30060
Barnet Dulaney Perkins Eye Center
Mesa, Arizona, 85206
VitreoRetinal Surgery PLLC;DBA Retina Consultants of Minnesota
Minneapolis, Minnesota, 55435
Northern California Retina-Vitreous Associates
Mountain View, California, 94040
Carolina Eyecare Physicians
Mt. Pleasant, South Carolina, 29464
Rocky Mountain Retina Consultants
Murray, Utah, 84107
Tennessee Retina
Nashville, Tennessee, 37203
New York University (NYU)
New York, New York, 10017
Wagner Kapoor Institute;Opthalmology
Norfolk, Virginia, 23502
East Bay Retina Consultants
Oakland, California, 94609
Ophthalmic Consultants of Long Island
Oceanside, New York, 11572
Doheny Eye Institute
Pasadena, California, 91105
California Eye Specialists Medical Group
Pasadena, California, 91107
Retina Specialty Institute
Pensacola, Florida, 32503
Mid Atlantic Retina
Philadelphia, Pennsylvania, 19107
Retinal Consultants of Arizona;Opthalmology
Phoenix, Arizona, 85014
Arizona Retina and Vitreous Consultants
Phoenix, Arizona, 85016
Associated Retina Consultants
Phoenix, Arizona, 85020
Fort Lauderdale Eye Institute
Plantation, Florida, 33324
Maine Eye Center
Portland, Maine, 04605
Retina Northwest;Research Department
Portland, Oregon, 97221
Sierra Eye Associates
Reno, Nevada, 89502
Retina Institute of Virginia
Richmond, Virginia, 23235
Associated Retinal Consultants - Royal Oak
Royal Oak, Michigan, 48073
Retina Consultants Medical Group
Sacramento, California, 95841
Retina Associates of Utah, PLLC;Clinical Research
Salt Lake City, Utah, 84107
Medical Center Ophthalmology Associates
San Antonio, Texas, 78240
Zuckerberg San Francisco General Hospital and Trauma Center
San Francisco, California, 94110
Orange County Retina Medical Group
Santa Ana, California, 92705
California Retina Consultants;Research Department
Santa Barbara, California, 93103
Pacific Northwest Retina
Silverdale, Washington, 98383
Spokane Eye Clinical Research;Spokane Eye Surgery Center
Spokane, Washington, 99204
Retina Institute
St Louis, Missouri, 63128
Retina Vitreous Associates of Florida
St. Petersburg, Florida, 33711
Southern Vitreoretinal Associates;Research
Tallahassee, Florida, 32308
Retina Associates of Florida;Retina Associates of Florida
Tampa, Florida, 33609
Retina Associates of New Jersey
Teaneck, New Jersey, 07666
Retina Specialist
Towson, Maryland, 21204
Retina Group of New England
Waterford, Connecticut, 06385
Palmetto Retina Center
West Columbia, South Carolina, 29169
Wolfe Eye Clinic
West Des Moines, Iowa, 50266
Vitreo Retinal Associates
Worcester, Massachusetts, 01605
About this study
Official title: 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 (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
- Being tested
- PDS Implant Pre-Filled with 100 mg/mL Ranibizumab, Intravitreal Ranibizumab 0.5 mg Injection, Ranibizumab refill exchange
- Keywords
- Port Delivery System
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PDS Implant Pre-Filled with 100 mg/mL RanibizumabDrug
Will be administered as per the schedule described in individual arm.
Intravitreal Ranibizumab 0.5 mg InjectionDrug
Will be administered as per the schedule described in individual arm.
Ranibizumab refill exchangeDrug
Will be administered as per the schedule described in individual arm.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Ranibizumab refill exchange |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to Week 64
Substudy: Number of Participants With Ocular and Systemic (Non-ocular) Adverse Events (AEs) and Severity of Ocular and Systemic AEs
Measured: Baseline to Week 72
Substudy: Number of Participants With Adverse Events of Special Interests (AESIs) and Severity of AESIs
Measured: Baseline to Week 72
Substudy: Duration of AESIs
Measured: Baseline to Week 72
Substudy: Number of Participants With Ocular AESIs and Severity of Ocular AESIs During the Post-operative Period
Measured: Up to Day 37 post re-implantation
Substudy: Number of Participants With Ocular AESIs and Severity of Ocular AESIs During the Follow-up Period
Measured: > 37 days post-implantation (up to approximately 72 weeks)
Substudy: Duration of Ocular AESIs During the Post-operative Period
Measured: Up to Day 37 post re-implantation
Substudy: Duration of Ocular AESIs During the Follow-up Period
Measured: > 37 days post-implantation (up to approximately 72 weeks)
Substudy: Number of Participants With Adverse Device Effects (ADEs) and Severity of ADEs
Measured: Baseline to Week 72
Substudy: Number of Participants With Anticipated Serious ADEs
Measured: Baseline to Week 72
Substudy: Duration of Serious ADEs
Measured: Baseline to Week 72
Substudy: Number of Device Deficiencies
Measured: 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
ETDRS-DRSS = ETDRS Diabetic Retinopathy Severity Scale
Measured: 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
Measured: 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
Measured: 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
Measured: Baseline to Week 64
Change from Baseline in BCVA as Measured on the ETDRS Chart Over Time
Measured: Baseline up to Week 120
Percentage of Participants Who Lose <15, <10, and <5 letters in BCVA From Baseline Over Time
Measured: Baseline up to Week 120
Percentage of Participants Who Gain ≥15, ≥10, ≥5, ≥0 Letters in BCVA From Baseline Over Time
Measured: Baseline up to Week 120
Percentage of Participants With a BCVA Snellen Equivalent of 20/40 or Better Over Time
Measured: Baseline up to Week 120
Percentage of Participants With a BCVA Snellen Equivalent of 20/200 or Worse Over Time
Measured: Baseline up to Week 120
Percentage of Participants With a ≥2-step Improvement From Baseline on the ETDRS-DRSS Over Time
Measured: Baseline up to Week 120
Percentage of Participants With a ≥3-step Improvement From Baseline on the ETDRS-DRSS Over Time
Measured: Baseline up to Week 120
Time to ≥2-step Worsening From Baseline on the ETDRS-DRSS
Measured: Baseline up to Week 120
Time to ≥3-step Worsening From Baseline on the ETDRS-DRSS
Measured: Baseline up to Week 120
Change From Baseline in ETDRS-DRSS Score Over Time
Measured: Baseline up to Week 120
Change From Baseline in Central Subfield Thickness (CST) as Measured on Spectral Domain Optical Coherence Tomography (SD-OCT) Over Time
Measured: Baseline up to Week 120
Change From Baseline in Total Macular Volume as Measured on SD-OCT Over Time
Measured: Baseline up to Week 120
Percentage of Participants With Absence of Intraretinal Fluid (IRF) Over Time (IRF as Measured in the Central 1 mm Subfield)
Measured: Baseline up to Week 120
Percentage of Participants With Absence of Subretinal Fluid (SRF) Over Time (SRF as Measured in the Central 1 mm Subfield)
Measured: Baseline up to Week 120
Percentage of Participants With Absence of IRF and SRF Over Time
Measured: 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
Measured: Baseline up to Week 120
Time to PDR (Defined as a Score ≥60 on the ETDRS-DRSS)
PDR = proliferative diabetic retinopathy
Measured: Baseline up to Week 120
Percentage of Participants Who do not Undergo Supplemental Treatment With IVT Ranibizumab Within Each Refill-exchange Interval
Measured: Baseline up to Week 120
Percentage of Participants Who Report Preferring PDS Treatment Compared With IVT Ranibizumab Treatment
As measured by the PDS patient preference questionnaire (PPPQ) at Week 64 among participants in the PDS arm efficacy population, mITT population
Measured: Baseline to Week 64
Percentage of Participants Who Report Preferring PDS Treatment Compared With IVT Ranibizumab Treatment, as Measured by the PPPQ at Week 64
Participants in a subset of patients with bilateral disease who are simultaneously receiving ranibizumab via study eye PDS implant and fellow eye IVT injection.
Measured: Baseline to Week 64
Participant-reported Vision-related Functioning and Health-Related Quality of Life (HRQoL) Among Participants 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
Measured: , Baseline Week 48, Week 96
Participant-reported Vision-related Functioning and HRQoL, as Measured by the Proportion of Participants With a ≥ 4-Point Improvement From Baseline in the NEI VFQ-25 Composite Score at Weeks 48 and 96 Among Participants in Both Treatment Arms
Measured: Baseline, Week 48, Week 96
Incidence and Severity of Ocular AEs
Measured: Baseline to Week 120
Incidence and Severity of Non-ocular AEs
Measured: Baseline up to Week 120
Incidence, Severity, and Duration of AEs of Special Interest
Measured: Baseline up to Week 120
Serum Concentration of Ranibizumab Observed Over Time
Measured: Baseline up to Week 120
PK Parameter: Value Area Under the Concentration- Time Curve Over 24 weeks (AUC24W)
Measured: Baseline to Week 24
PK Parameter: Maximum Serum Concentration (Cmax)
Measured: Baseline up to Week 120
PK Parameter: Minimum Serum Concentration (Cmin)
Measured: Baseline up to Week 120
Time of Maximum Observed Serum Concentration (Tmax) After PDS Implant Insertion
Measured: Baseline up to Week 120
Prevalence of Anti-drug Antibodies (ADAs) at Baseline and Incidence of ADAs During the Study
Measured: Baseline up to Week 120
Prevalence of Neutralizing Antibodies at Baseline and Incidence of Neutralizing Antibodies During the Study
Measured: Baseline up to Week 120
Reported Incidence of Device Deficiencies
Measured: Baseline up to Week 120
Incidence and Severity of Ocular AEs
Measured: Baseline up to Week 120
Incidence, Severity, and Duration of AESIs
Measured: Baseline up to Week 120
Incidence, Severity, and Duration of Ocular AESIs During the Postoperative Period (up to 37 Days After Initial Implantation) and Follow-up Period (> 37 days After Implantation Surgery)
Measured: Baseline up to Week 120
Incidence and Severity of ADEs
Measured: Baseline up to Week 120
Incidence, Causality, Severity, and Duration of Anticipated Serious ADEs
Measured: Baseline up to Week 120
Substudy: Number of Participants With Ocular AESIs and Severity of Ocular AESIs After Refill-exchange Procedure
Measured: Up to approximately 72 weeks
Substudy: Duration of AESIs After Refill-exchange Procedure
Measured: Up to approximately 72 weeks
Substudy: Number of Participants With ADEs and Severity of ADEs After Refill-exchange Procedure
Measured: Up to approximately 72 weeks
Substudy: Number of Participants With Anticipated Serious ADEs After Refill-exchange Procedure
Measured: Up to approximately 72 weeks
Substudy: Duration of Serious ADEs After Refill-exchange Procedure
Measured: Up to approximately 72 weeks
Substudy: Number of Device Deficiencies After Refill-exchange Procedure
Measured: Up to approximately 72 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2019
- Study start30 Sep 2019
- Primary completion20 Jul 2027 (estimated)
- Study completion20 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Diabetic Macular EdemaStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 672 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04108156
- Sponsor's protocol ID
- GR40550
- Acronym
- Pagoda
- Status last verified
- Oct 2026
- First submitted
- 26 Sep 2019
- Last updated
- 8 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing
Publications
Rustam Z, Khanani AM, Mojumder O, Huddleston S, Scott M, Marcus DM, Kapoor KG, Whitaker S, Awh CC, Walden L, Clark WL, Saini AM, Graff J, Miranda MC, Lin A, Blotner S, Rabena M, Gune S, Campochiaro PA. Time Course of Resolution of Diabetic Macular Edema by Sustained Suppression of VEGF-A with the Port Delivery Platform with Ranibizumab. Am J Ophthalmol. 2026 Oct 27:S0002-9394(26)00589-1. doi: 10.1016/j.ajo.2026.10.021. Online ahead of print.
PubMed 42946032Khanani 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.
PubMed 40048197Stockwell 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.
PubMed 37585454
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT04108156
- Acronym / sponsor ID
- Pagoda / GR40550
- Conditions
- Diabetic Macular Edema
- Keywords
- Port Delivery System
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 672 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 30 Sep 2019 (actual)
- Primary completion
- 20 Jul 2027 (estimated)
- Study completion
- 20 Jul 2027 (estimated)
- First posted
- 30 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| PDS Arm | Experimental | Drug: PDS Implant Pre-Filled with 100 mg/mL Ranibizumab, Drug: Ranibizumab refill exchangeParticipants 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. |
| Intravitreal Arm | Active comparator | Drug: Intravitreal Ranibizumab 0.5 mg Injection, Drug: Ranibizumab refill exchangeParticipants 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. |
| Substudy: Cohort 1 | Experimental | Drug: PDS Implant Pre-Filled with 100 mg/mL Ranibizumab, Drug: Ranibizumab refill exchangeParticipants 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. |
| Substudy: Cohort 2a | Experimental | Drug: Ranibizumab refill exchangeParticipants 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. |
| Substudy: Cohort 2b | Experimental | Drug: Ranibizumab refill exchangeParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PDS Implant Pre-Filled with 100 mg/mL RanibizumabWill be administered as per the schedule described in individual arm. | Drug | PDS Arm, Substudy: Cohort 1 |
| Intravitreal Ranibizumab 0.5 mg InjectionWill be administered as per the schedule described in individual arm. | Drug | Intravitreal Arm |
| Ranibizumab refill exchangeWill be administered as per the schedule described in individual arm. | Drug | Intravitreal Arm, PDS Arm, Substudy: Cohort 1, Substudy: Cohort 2a, Substudy: Cohort 2b |
Primary outcome
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
Time frame: Baseline to Week 64
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.
Substudy: Number of Participants With Ocular and Systemic (Non-ocular) Adverse Events (AEs) and Severity of Ocular and Systemic AEs
Time frame: Baseline to Week 72
Substudy: Number of Participants With Adverse Events of Special Interests (AESIs) and Severity of AESIs
Time frame: Baseline to Week 72
Substudy: Duration of AESIs
Time frame: Baseline to Week 72
Substudy: Number of Participants With Ocular AESIs and Severity of Ocular AESIs During the Post-operative Period
Time frame: Up to Day 37 post re-implantation
Substudy: Number of Participants With Ocular AESIs and Severity of Ocular AESIs During the Follow-up Period
Time frame: > 37 days post-implantation (up to approximately 72 weeks)
Substudy: Duration of Ocular AESIs During the Post-operative Period
Time frame: Up to Day 37 post re-implantation
Substudy: Duration of Ocular AESIs During the Follow-up Period
Time frame: > 37 days post-implantation (up to approximately 72 weeks)
Substudy: Number of Participants With Adverse Device Effects (ADEs) and Severity of ADEs
Time frame: Baseline to Week 72
Substudy: Number of Participants With Anticipated Serious ADEs
Time frame: Baseline to Week 72
Substudy: Duration of Serious ADEs
Time frame: Baseline to Week 72
Substudy: Number of Device Deficiencies
Time frame: Baseline to Week 72
48 secondary outcomes
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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Baseline to Week 64
Change from Baseline in BCVA as Measured on the ETDRS Chart Over Time
Time frame: Baseline up to Week 120
Percentage of Participants Who Lose <15, <10, and <5 letters in BCVA From Baseline Over Time
Time frame: Baseline up to Week 120
Percentage of Participants Who Gain ≥15, ≥10, ≥5, ≥0 Letters in BCVA From Baseline Over Time
Time frame: Baseline up to Week 120
Percentage of Participants With a BCVA Snellen Equivalent of 20/40 or Better Over Time
Time frame: Baseline up to Week 120
Percentage of Participants With a BCVA Snellen Equivalent of 20/200 or Worse Over Time
Time frame: Baseline up to Week 120
Percentage of Participants With a ≥2-step Improvement From Baseline on the ETDRS-DRSS Over Time
Time frame: Baseline up to Week 120
Percentage of Participants With a ≥3-step Improvement From Baseline on the ETDRS-DRSS Over Time
Time frame: Baseline up to Week 120
Time to ≥2-step Worsening From Baseline on the ETDRS-DRSS
Time frame: Baseline up to Week 120
Time to ≥3-step Worsening From Baseline on the ETDRS-DRSS
Time frame: Baseline up to Week 120
Change From Baseline in ETDRS-DRSS Score Over Time
Time frame: Baseline up to Week 120
Change From Baseline in Central Subfield Thickness (CST) as Measured on Spectral Domain Optical Coherence Tomography (SD-OCT) Over Time
Time frame: Baseline up to Week 120
Change From Baseline in Total Macular Volume as Measured on SD-OCT Over Time
Time frame: Baseline up to Week 120
Percentage of Participants With Absence of Intraretinal Fluid (IRF) Over Time (IRF as Measured in the Central 1 mm Subfield)
Time frame: Baseline up to Week 120
Percentage of Participants With Absence of Subretinal Fluid (SRF) Over Time (SRF as Measured in the Central 1 mm Subfield)
Time frame: Baseline up to Week 120
Percentage of Participants With Absence of IRF and SRF Over Time
Time frame: Baseline up to Week 120
Percentage of Participants With Absence DME (Defined as CST ≥325 μm on SD-OCT) Over Time
Time frame: Baseline up to Week 120
Time to PDR (Defined as a Score ≥60 on the ETDRS-DRSS)
Time frame: Baseline up to Week 120
Percentage of Participants Who do not Undergo Supplemental Treatment With IVT Ranibizumab Within Each Refill-exchange Interval
Time frame: Baseline up to Week 120
Percentage of Participants Who Report Preferring PDS Treatment Compared With IVT Ranibizumab Treatment
Time frame: Baseline to Week 64
Percentage of Participants Who Report Preferring PDS Treatment Compared With IVT Ranibizumab Treatment, as Measured by the PPPQ at Week 64
Time frame: Baseline to Week 64
Participant-reported Vision-related Functioning and Health-Related Quality of Life (HRQoL) Among Participants in Both Treatment Arms, as Measured by Changes From Baseline
Time frame: , Baseline Week 48, Week 96
Participant-reported Vision-related Functioning and HRQoL, as Measured by the Proportion of Participants With a ≥ 4-Point Improvement From Baseline in the NEI VFQ-25 Composite Score at Weeks 48 and 96 Among Participants in Both Treatment Arms
Time frame: Baseline, Week 48, Week 96
Incidence and Severity of Ocular AEs
Time frame: Baseline to Week 120
Incidence and Severity of Non-ocular AEs
Time frame: Baseline up to Week 120
Incidence, Severity, and Duration of AEs of Special Interest
Time frame: Baseline up to Week 120
Serum Concentration of Ranibizumab Observed Over Time
Time frame: Baseline up to Week 120
PK Parameter: Value Area Under the Concentration- Time Curve Over 24 weeks (AUC24W)
Time frame: Baseline to Week 24
PK Parameter: Maximum Serum Concentration (Cmax)
Time frame: Baseline up to Week 120
PK Parameter: Minimum Serum Concentration (Cmin)
Time frame: Baseline up to Week 120
Time of Maximum Observed Serum Concentration (Tmax) After PDS Implant Insertion
Time frame: Baseline up to Week 120
Prevalence of Anti-drug Antibodies (ADAs) at Baseline and Incidence of ADAs During the Study
Time frame: Baseline up to Week 120
Prevalence of Neutralizing Antibodies at Baseline and Incidence of Neutralizing Antibodies During the Study
Time frame: Baseline up to Week 120
Reported Incidence of Device Deficiencies
Time frame: Baseline up to Week 120
Incidence and Severity of Ocular AEs
Time frame: Baseline up to Week 120
Incidence, Severity, and Duration of AESIs
Time frame: Baseline up to Week 120
Incidence, Severity, and Duration of Ocular AESIs During the Postoperative Period (up to 37 Days After Initial Implantation) and Follow-up Period (> 37 days After Implantation Surgery)
Time frame: Baseline up to Week 120
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2026.
- Derived from this study: PubMed 42946032Rustam Z, Khanani AM, Mojumder O, Huddleston S, Scott M, Marcus DM, Kapoor KG, Whitaker S, Awh CC, Walden L, Clark WL, Saini AM, Graff J, Miranda MC, Lin A, Blotner S, Rabena M, Gune S, Campochiaro PA. Time Course of Resolution of Diabetic Macular Edema by Sustained Suppression of VEGF-A with the Port Delivery Platform with Ranibizumab. Am J Ophthalmol. 2026 Oct 27:S0002-9394(26)00589-1. doi: 10.1016/j.ajo.2026.10.021. Online ahead of print.
- Derived from this study: PubMed 40048197Khanani 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.
- Derived from this study: PubMed 37585454Stockwell 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.
- Individual participant dataSharing planned: Yes. For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing
Related trials for Diabetic Macular Edema
Active, not recruitingObservational study
Real World Evidence in China: Faricimab Use in Diabetic Macular Edema, Retinal Vein Occlusion, and Neovascular Age-Related Macular Degeneration (The Farseeing Study)
Diabetic Macular Edema, Neovascular Age-related Macular Degeneration
Active, not recruitingPhase 2
Long-Term Follow-Up Study of RGX-314 Administered in the Suprachoroidal Space for Participants With and Without Diabetic Retinopathy
Diabetic Retinopathy, DR
RecruitingPhase 3
A Phase 3 Trial for Intravitreal Injection of 4D-150 in Adults With Diabetic Macular Edema (DME).
Diabetic Macular Edema (DME)
RecruitingPhase 2
Oral N-Acetylcysteine on Diabetic Macular Edema
Diabetic Macular Edema (DME)
Active, not recruitingPhase 3
COMO: A Phase 3 Randomized, Double-Masked Study Comparing the Efficacy of EYP-1901 Against Aflibercept in DME
Diabetic Macular Edema, DME
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
89 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing PDS Implant Pre-Filled with 100 mg/mL Ranibizumab, Intravitreal Ranibizumab 0.5 mg Injection and Ranibizumab refill exchange in people with Diabetic Macular Edema, run by Hoffmann-La Roche at 89 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 8 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 89 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: Baseline to Week 64). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04108156, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2026.