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

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04108156
Collaborator
(none)
634
90
2
52.8
7
0.1

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
  • Drug: PDS Implant Pre-Filled with 100 mg/mL Ranibizumab
  • Drug: Intravitreal Ranibizumab 0.5 mg Injection
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
634 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Outcomes Assessor)
Primary Purpose:
Treatment
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)
Actual Study Start Date :
Sep 30, 2019
Anticipated Primary Completion Date :
Sep 16, 2022
Anticipated Study Completion Date :
Feb 23, 2024

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

  1. 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

  1. 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

  2. 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]

  3. 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]

  4. 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]

  5. Change from baseline in BCVA as measured on the ETDRS chart over time [Baseline up to Week 120]

  6. Percentage of participants who lose <15, <10, and <5 letters in BCVA from baseline over time [Baseline up to Week 120]

  7. Percentage of participants who gain ≥15, ≥10, ≥5, ≥0 letters in BCVA from baseline over time [Baseline up to Week 120]

  8. Percentage of participants with a BCVA Snellen equivalent of 20/40 or better over time [Baseline up to Week 120]

  9. Percentage of participants with a BCVA Snellen equivalent of 20/200 or worse over time [Baseline up to Week 120]

  10. Percentage of participants with a ≥2-step improvement from baseline on the ETDRS-DRSS over time [Baseline up to Week 120]

  11. Percentage of participants with a ≥3-step improvement from baseline on the ETDRS-DRSS over time [Baseline up to Week 120]

  12. Time to ≥2-step worsening from baseline on the ETDRS-DRSS [Baseline up to Week 120]

  13. Time to ≥3-step worsening from baseline on the ETDRS-DRSS [Baseline up to Week 120]

  14. Change from baseline in ETDRS-DRSS score over time [Baseline up to Week 120]

  15. Change from baseline in CST as measured on SD-OCT over time [Baseline up to Week 120]

  16. Change from baseline in total macular volume as measured on SD-OCT over time [Baseline up to Week 120]

  17. 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]

  18. 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]

  19. Percentage of participants with absence of intraretinal fluid and subretinal fluid over time [Baseline up to Week 120]

  20. 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

  21. Time to PDR (defined as a score ≥60 on the ETDRS-DRSS) [Baseline up to Week 120]

    PDR = proliferative diabetic retinopathy

  22. Percentage of participants who do not undergo supplemental treatment with intravitreal ranibizumab within each refill-exchange interval [Baseline up to Week 120]

  23. 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

  24. 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

  25. 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

  26. 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]

  27. Incidence and severity of ocular adverse events [Baseline to Week 120]

  28. Incidence and severity of non-ocular adverse events [Baseline up to Week 120]

  29. Incidence, severity, and duration of adverse events of special interest [Baseline up to Week 120]

  30. Serum concentration of ranibizumab observed over time [Baseline up to Week 120]

  31. PK parameter value area under the concentration- time curve over 24 weeks (AUC24W) [Baseline to Week 24]

  32. Pharmacokinetic (PK) parameter maximum serum concentration (Cmax) [Baseline up to Week 120]

  33. PK Parameter minimum serum concentration (Cmin) [Baseline up to Week 120]

  34. Time of maximum observed serum concentration (Tmax) after PDS implant insertion [Baseline up to Week 120]

  35. Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs during the study [Baseline up to Week 120]

  36. Prevalence of neutralizing antibodies at baseline and incidence of neutralizing antibodies during the study [Baseline up to Week 120]

  37. Reported incidence of device deficiencies [Baseline up to Week 120]

  38. Incidence and severity of ocular adverse events [Baseline up to Week 120]

  39. 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]

  40. Incidence and severity of adverse device effects [Baseline up to Week 120]

  41. Incidence, causality, severity, and duration of anticipated serious adverse device effects [Baseline up to Week 120]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
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.
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT04108156
Other Study ID Numbers:
  • GR40550
First Posted:
Sep 30, 2019
Last Update Posted:
Aug 15, 2022
Last Verified:
Jul 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Hoffmann-La Roche
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 15, 2022