Pagoda: 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
Study Details
Study Description
Brief Summary
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).
Condition or Disease | Intervention/Treatment | Phase |
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Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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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.
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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.
|
Outcome Measures
Primary Outcome Measures
- 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 [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.
Secondary Outcome Measures
- 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]
ETDRS-DRSS = ETDRS Diabetic Retinopathy Severity Scale
- 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 [Baseline up to Week 120]
DME = diabetic macular edema
- Time to PDR (defined as a score ≥60 on the ETDRS-DRSS) [Baseline up to Week 120]
PDR = proliferative diabetic retinopathy
- 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 [Baseline to Week 64]
As measured by the PDS Patient Preference Questionnaire at Week 64 among patients in the PDS arm efficacy population, mITT population
- 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 [Baseline to 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
- Patient-reported vision-related functioning and health-related quality of life (HRQoL) among patients in both treatment arms, as measured by changes from baseline [, Baseline Week 48, Week 96]
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
- 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]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age ≥18 years at time of signing Informed Consent Form
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Documented diagnosis of diabetes mellitus (Type 1 or Type 2)
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HbA1c level of ≤10% within 2 months prior to screening or at screening
Study eye
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Macular thickening secondary to DME involving the center of the fovea with CST ≥325 um on SD-OCT at screening
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BCVA score of 78 to 25 letters (20/32 to 20/320 approximate Snellen equivalent)
Exclusion Criteria:
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High-risk proliferative diabetic retinopathy
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Active intraocular inflammation (grade trace or above)
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Suspected or active ocular or periocular infection of either eye
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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
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Cerebrovascular accident or myocardial infarction within 6 months prior to randomization
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Atrial fibrillation diagnosis or worsening within 6 months prior to randomization
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Uncontrolled blood pressure
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Barnet Dulaney Perkins Eye Center | Mesa | Arizona | United States | 85206 |
2 | Associated Retina Consultants | Phoenix | Arizona | United States | 85020 |
3 | Arizona Retina and Vitreous Consultants | Phoenix | Arizona | United States | 85021 |
4 | Retinal Consultants of Arizona | Phoenix | Arizona | United States | 85053 |
5 | California Retina Consultants | Bakersfield | California | United States | 93309 |
6 | Retina-Vitreous Associates Medical Group | Beverly Hills | California | United States | 90211 |
7 | The Retina Partners | Encino | California | United States | 91436 |
8 | Retina Consultants of Orange County | Fullerton | California | United States | 92835 |
9 | N CA Retina Vitreous Assoc | Mountain View | California | United States | 94040 |
10 | East Bay Retina Consultants | Oakland | California | United States | 94609 |
11 | Doheny Eye Institute | Pasadena | California | United States | 91105 |
12 | California Eye Specialists Medical group Inc. | Pasadena | California | United States | 91107 |
13 | Retinal Consultants Med Group | Sacramento | California | United States | 95825 |
14 | Zuckerberg San Francisco General Hospital | San Francisco | California | United States | 94110 |
15 | Orange County Retina Med Group | Santa Ana | California | United States | 92705 |
16 | California Retina Consultants | Santa Barbara | California | United States | 93103 |
17 | Eye Center of Northern CO | Fort Collins | Colorado | United States | 80528 |
18 | Colorado Retina Associates, PC | Lakewood | Colorado | United States | 80228 |
19 | Retina Group of New England | Waterford | Connecticut | United States | 06385 |
20 | Retina Group of Florida | Fort Lauderdale | Florida | United States | 33308 |
21 | National Ophthalmic Research Institute | Fort Myers | Florida | United States | 33912 |
22 | Retina Specialty Institute | Pensacola | Florida | United States | 32503 |
23 | Fort Lauderdale Eye Institute | Plantation | Florida | United States | 33324 |
24 | Retina Vitreous Assoc of FL | Saint Petersburg | Florida | United States | 33711 |
25 | Southern Vitreoretinal Assoc | Tallahassee | Florida | United States | 32308 |
26 | Retina Associates of Florida, LLC | Tampa | Florida | United States | 33609 |
27 | Southeast Retina Center | Augusta | Georgia | United States | 30909 |
28 | Georgia Retina PC | Marietta | Georgia | United States | 30060 |
29 | Northwestern Medical Group/Northwestern University | Chicago | Illinois | United States | 60611 |
30 | Illinois Retina Associates | Joliet | Illinois | United States | 60435 |
31 | University Retina and Macula Associates, PC | Lemont | Illinois | United States | 60439 |
32 | Wolfe Eye Clinic | West Des Moines | Iowa | United States | 50266 |
33 | Retina Associates | Lenexa | Kansas | United States | 66215 |
34 | Retina Associates of Kentucky | Lexington | Kentucky | United States | 40509 |
35 | Maine Eye Center | Portland | Maine | United States | 04101 |
36 | The Retina Care Center | Baltimore | Maryland | United States | 21209 |
37 | Johns Hopkins Med; Wilmer Eye Inst | Baltimore | Maryland | United States | 21287 |
38 | Retina Group of Washington | Chevy Chase | Maryland | United States | 20815 |
39 | Cumberland Valley Retina Associates | Hagerstown | Maryland | United States | 21740 |
40 | Retina Specialists | Towson | Maryland | United States | 21204 |
41 | Tufts Medical Center | Boston | Massachusetts | United States | 02111 |
42 | Ophthalmic Consultants of Boston | Boston | Massachusetts | United States | 02114 |
43 | Vitreo-Retinal Associates, PC | Worcester | Massachusetts | United States | 01605 |
44 | Associated Retinal Consultants | Grand Rapids | Michigan | United States | 49546 |
45 | Foundation for Vision Research | Grand Rapids | Michigan | United States | 49546 |
46 | Vitreo Retinal Surgery | Minneapolis | Minnesota | United States | 55435 |
47 | Midwest Vision Research Foundation | Chesterfield | Missouri | United States | 63017 |
48 | The Retina Institute | Saint Louis | Missouri | United States | 63128 |
49 | Sierra Eye Associates | Reno | Nevada | United States | 89502 |
50 | Envision Ocular, LLC | Bloomfield | New Jersey | United States | 07003 |
51 | Retina Associates of NJ | Teaneck | New Jersey | United States | 07666 |
52 | Long Is. Vitreoretinal Consult | Great Neck | New York | United States | 11021 |
53 | Retina Vit Surgeons/Central NY | Liverpool | New York | United States | 13088 |
54 | New York University | New York | New York | United States | 10017 |
55 | Ophthalmic Cons of Long Island | Oceanside | New York | United States | 11572 |
56 | Western Carolina Retinal Associate PA | Asheville | North Carolina | United States | 28803 |
57 | Char Eye Ear &Throat Assoc | Charlotte | North Carolina | United States | 28210 |
58 | Duke Eye Center | Durham | North Carolina | United States | 27705 |
59 | Graystone Eye | Hickory | North Carolina | United States | 28602 |
60 | Cape Fear Retinal Associates | Wilmington | North Carolina | United States | 28401 |
61 | Cincinnati Eye Institute | Cincinnati | Ohio | United States | 45242 |
62 | Cleveland Clinic Foundation; Cole Eye Institute | Cleveland | Ohio | United States | 44195 |
63 | The Ohio State University | Columbus | Ohio | United States | 43210 |
64 | Midwest Retina | Dublin | Ohio | United States | 43016 |
65 | Retina Vitreous Center | Edmond | Oklahoma | United States | 73013 |
66 | Retina Northwest | Portland | Oregon | United States | 97221 |
67 | Cumberland Valley Retina Consultants; Chambersburg | Chambersburg | Pennsylvania | United States | 17201 |
68 | Mid Atlantic Retina | Philadelphia | Pennsylvania | United States | 19107 |
69 | Palmetto Retina Center | Florence | South Carolina | United States | 29501 |
70 | Charleston Neuroscience Inst | Ladson | South Carolina | United States | 29456 |
71 | Carolina Eyecare Physicians | Mount Pleasant | South Carolina | United States | 29464 |
72 | Charles Retina Institute | Memphis | Tennessee | United States | 38119 |
73 | Tennessee Retina PC | Nashville | Tennessee | United States | 37203 |
74 | Retina Res Institute of Texas | Abilene | Texas | United States | 79606 |
75 | Texas Retina Associates | Arlington | Texas | United States | 76012 |
76 | Austin Research Center for Retina | Austin | Texas | United States | 78705 |
77 | Austin Retina Associates | Austin | Texas | United States | 78705 |
78 | Austin Clinical Research LLC | Austin | Texas | United States | 78750 |
79 | Retina Consultants of Texas | Bellaire | Texas | United States | 77401 |
80 | Texas Retina Associates | Dallas | Texas | United States | 75231 |
81 | Texas Retina Associates | Fort Worth | Texas | United States | 76104 |
82 | Retina & Vitreous of Texas | Houston | Texas | United States | 77025 |
83 | Med Center Ophthalmology Assoc | San Antonio | Texas | United States | 78240 |
84 | Retina Associates of Utah | Salt Lake City | Utah | United States | 84107 |
85 | Rocky Mountain Retina | Salt Lake City | Utah | United States | 84107 |
86 | Piedmont Eye Center | Lynchburg | Virginia | United States | 24502 |
87 | Wagner Macula & Retina Center | Norfolk | Virginia | United States | 23502 |
88 | Retina Institute of Virginia | Richmond | Virginia | United States | 23235 |
89 | Retina Center Northwest | Silverdale | Washington | United States | 98383 |
90 | Spokane Eye Clinical Research | Spokane | Washington | United States | 99204 |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GR40550