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PAVILION: A Multicenter, Randomized Study in Participants With Diabetic Retinopathy Without Center-involved Diabetic Macular Edema To Evaluate the Efficacy, Safety, and Pharmacokinetics of Ranibizumab Delivered Via the Port Delivery System Relative to the Comparator Arm

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04503551
Collaborator
(none)
174
Enrollment
76
Locations
2
Arms
44.9
Anticipated Duration (Months)
2.3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Study GR41675 is a Multicenter, Randomized Study in Participants with Diabetic Retinopathy (DR) Without Center-Involved Diabetic Macular Edema (CI-DME) to Evaluate the Efficacy, Safety of the Port Delivery System with Ranibizumab (PDS) Relative to the Comparator Arm

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 :
174 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Outcomes Assessor)
Masking Description:
The visual acuity examiner will only conduct refraction and visual acuity assessments and will be masked, as best as possible, to the following items: study eye assignment; study visit type; and treatment assignment.
Primary Purpose:
Treatment
Official Title:
A Phase III, Multicenter, Randomized Study of the Efficacy, Safety, and Pharmacokinetics of the Port Delivery System With Ranibizumab in Patients With Diabetic Retinopathy
Actual Study Start Date :
Aug 10, 2020
Anticipated Primary Completion Date :
Sep 30, 2022
Anticipated Study Completion Date :
May 7, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: PDS Arm

Participants randomized to the PDS arm will receive two intravitreal ranibizumab injections 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 36-weeks (Q36W) thereafter

Drug: PDS Implant Pre-Filled with 100 mg/mL Ranibizumab
Will be administered as per the schedule described in individual arm.

Drug: Intravitreal Ranibizumab 0.5 mg Injection
Will be administered as per the schedule described in individual arm.
Other: Comparator Arm

Participants randomized to the comparator arm will undergo study visits every 4 weeks (Q4W) for comprehensive clinical monitoring until they receive the PDS implant (pre-filled with ranibizumab). PDS implant refill-exchange procedures will be performed on a fixed interval Q36W thereafter. Participants will be eligible to receive intravitreal ranibizumab 0.5 mg injections if treatment eligibility criteria are met.

Drug: PDS Implant Pre-Filled with 100 mg/mL Ranibizumab
Will be administered as per the schedule described in individual arm.

Drug: Intravitreal Ranibizumab 0.5 mg Injection
Will be administered as per the schedule described in individual arm.

Outcome Measures

Primary Outcome Measures

  1. Percentage of participants with a ≥2-step improvement from baseline on the ETDRS-DRSS at Week 52 [Week 52]

    ETDRS = Early Treatment Diabetic Retinopathy Study DRSS = Diabetic Retinopathy Severity Scale The ETDRS-DRSS includes 13 score levels, ranging from the absence of retinopathy to PDR, including neovascularization and/or vitreous/preretinal hemorrhage.

Secondary Outcome Measures

  1. Rate of participants developing a vision-threatening complication (defined as PDR, ASNV, or CI-DME [defined as central foveal thickness [CST] ≥325 μm on spectral-domain optical coherence tomography [SD-OCT]) through Week 52 [From baseline through 52 weeks]

    PDR = proliferative diabetic retinopathy ASNV = Anterior segment neovascularization

  2. Rate of participants developing PDR or ASNV through Week 52 [From baseline through 52 weeks]

  3. Rate of participants developing CI-DME through Week 52 [From baseline through 52 weeks]

  4. Rate of participants developing a ≥ 2-step worsening from baseline on the ETDRS-DRSS through Week 52 [From baseline through 52 weeks]

  5. Percentage of participants with a ≥ 3-step improvement from baseline on the ETDRS-DRSS at Week 52 [Week 52]

  6. Rate of participants developing a ≥ 3-step worsening from baseline on the ETDRS-DRSS through Week 52 [Baseline up to 52 weeks]

  7. Percentage of participants with a ≥ 2-step improvement from baseline on the ETDRS-DRSS over time [Baseline up to Week 112]

  8. Percentage of participants with a ≥ 3-step improvement from baseline on the ETDRS-DRSS over time [Baseline up to Week 112]

  9. Time to first development of either PDR, ASNV, or CI-DME [Baseline up to Week 112]

  10. Time to first development of PDR or ASNV [Baseline up to Week 112]

  11. Time to first development of CI-DME [Baseline up to Week 112]

  12. Time to first development of a ≥ 2-step worsening from baseline on the ETDRS-DRSS [Baseline up to Week 112]

  13. Time to first development of a ≥ 3-step worsening from baseline on the ETDRS-DRSS [Baseline up to Week 112]

  14. Change from baseline in Best-Corrected Visual Acuity (BCVA) as measured on the ETDRS chart over time [Baseline up to Week 112]

    A vision score of 20/20 vision is considered normal. A score of 20/200 is considered being legally blind.

  15. Percentage of participants who lose <15, < 10 and < 5 letters in BCVA from baseline over time [Baseline up to Week 112]

  16. Percentage of participants with a BCVA score of 69 letters (20/40 approximate Snellen equivalent) or better over time [Baseline up to Week 112]

  17. Change from baseline in CST as measured on SD-OCT over time [Baseline up to Week 112]

  18. Change from baseline in total macular volume as measured on SD-OCT over time [Baseline up to Week 112]

  19. Incidence and severity of ocular adverse events [Baseline up to Week 112]

  20. Incidence and severity of non-ocular adverse events [Baseline up to Week 112]

  21. Incidence, severity, and duration of adverse events of special interest [Baseline up to Week 112]

  22. Incidence, severity, and duration of ocular adverse events of special interest during the postoperative period (≤ 37 days after initial implant insertion) and follow-up period (> 37 days after implant insertion surgery) [Baseline up to Week 112]

  23. Serum concentration of ranibizumab observed over time [Baseline up to Week 112]

  24. Pharmacokinetic (PK) parameter value area under the concentration- time curve [Baseline up to Week 112]

  25. PK Parameter minimum serum concentration (Cmin) [Baseline up to Week 112]

  26. PK parameter half-life (t1/2) after PDS implant insertion [Baseline up to Week 112]

  27. Prevalence of anti-drug antibodies (ADAs) prior to study treatment and incidence of ADAs after study treatment [Baseline up to Week 112]

  28. Prevalence of neutralizing antibodies at baseline and incidence of neutralizing antibodies during the study [Baseline up to Week 112]

  29. Percentage of participants who do not undergo supplemental treatment with intravitreal ranibizumab within each refill-exchange interval [Baseline up to Week 112]

  30. Percentage of participants with adverse device effects [Baseline up to Week 112]

  31. Percentage of participants with serious adverse device effects [Baseline up to Week 112]

  32. Percentage of participants with absence of intraretinal fluid, subretinal fluid or both (as measured in the central 1 mm subfield) over time [Baseline up to Week 112]

  33. Percentage of participants who report preferring PDS treatment to intravitreal ranibizumab treatment, as measured by the PPPQ at Week 52 [Week 52]

  34. Reported incidence of device deficiencies [Baseline up to Week 52]

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 ≤12% within 2 months prior to screening or at screening

Inclusion Criteria for Study Eye

  • Moderately severe or severe NPDR (ETDRS-DRSS level 47 or 53)

  • BCVA score of ≥ 69 letters (20/40 approximate Snellen equivalent or better)

Exclusion Criteria:

  • Uncontrolled blood pressure

  • Cerebrovascular accident or myocardial infarction within 6 months prior to randomization

  • Atrial fibrillation diagnosis or worsening within 6 months prior to randomization

  • Current systemic treatment for a confirmed active systemic infection

  • Renal failure requiring renal transplant, hemodialysis, or peritoneal dialysis, or anticipated to require hemodialysis or peritoneal dialysis at any time during the study

  • History 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 patient at high risk for treatment complications in the opinion of the investigator or Sponsor

Ocular Exclusion Criteria for Study Eye:

  • Presence of center-involved diabetic macular edema (defined as CST ≥325 µm)

  • Any intravitreal anti-VEGF treatment at any time prior to randomization

  • Any use of medicated intraocular implants, including Ozurdex® or Iluvien® implants at any time prior to randomization

  • Any intravitreal corticosteroid treatment at any time prior to randomization

  • Any periocular (e.g., subtenon) corticosteroid treatment at any time prior to randomization

  • Any PRP at any time prior to randomization

  • Any macular laser photocoagulation (such as micropulse and focal or grid laser) at any time prior to randomization

  • Active intraocular inflammation (grade trace or above)

  • Clinically significant abnormalities of the vitreous-retinal interface involving the macular area or disrupting the macular architecture, such as vitreous-retinal traction or epiretinal membrane (assessed by the investigator and confirmed by the central reading center)

  • Uncontrolled ocular hypertension or glaucoma and any such condition the investigator determines may require a glaucoma-filtering surgery during a participant's participation in the study

  • History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery

  • Any concurrent ocular condition (e.g., cataract, epiretinal membrane) that would require surgical intervention during the study to prevent or treat visual loss that might result from that condition

  • Any concurrent ocular condition (e.g., amblyopia, strabismus) that may affect interpretation of study results

  • History of other ocular diseases that gives reasonable suspicion of a disease or condition that contraindicates the use of ranibizumab, that might affect interpretation of study results, or that renders the participant at high risk for treatment complications

Ocular Exclusion Criteria for Either Eye

  • Suspected or active ocular or periocular infection of either eye

  • Any history uveitis including idiopathic, drug-associated or autoimmune-associated uveitis

Contacts and Locations

Locations

Site City State Country Postal Code
1 Trinity Research Group Dothan Alabama United States 36301
2 Barnet Dulaney Perkins Eye Center Mesa Arizona United States 85206
3 Associated Retina Consultants Phoenix Arizona United States 85020
4 California Retina Consultants Bakersfield California United States 93309
5 The Retina Partners Encino California United States 91436
6 Retina Consultants of Orange County Fullerton California United States 92835
7 Jules Stein Eye Institute/ UCLA Los Angeles California United States 90095-7000
8 California Eye Specialists Medical group Inc. Pasadena California United States 91107
9 Kaiser Permanente Riverside Medical Center Riverside California United States 92505
10 Retinal Consultants Med Group Sacramento California United States 95825
11 Zuckerberg San Francisco General Hospital San Francisco California United States 94110
12 Orange County Retina Med Group Santa Ana California United States 92705
13 California Retina Consultants Santa Barbara California United States 93103
14 University of Colorado Aurora Colorado United States 80045
15 Southwest Retina Consultants Durango Colorado United States 81303
16 Eye Center of Northern CO Fort Collins Colorado United States 80528
17 Colorado Retina Associates, PC Lakewood Colorado United States 80228
18 Retina Group of New England Waterford Connecticut United States 06385
19 Retina Specialty Institute Pensacola Florida United States 32503
20 Fort Lauderdale Eye Institute Plantation Florida United States 33324
21 Southern Vitreoretinal Assoc Tallahassee Florida United States 32308
22 Retina Associates of Florida, LLC Tampa Florida United States 33609
23 Southeast Retina Center Augusta Georgia United States 30909
24 Georgia Retina PC Marietta Georgia United States 30060
25 Retina Consultants of Hawaii 'Aiea Hawaii United States 96701
26 Northwestern Medical Group/Northwestern University Chicago Illinois United States 60611
27 Illinois Retina Associates Joliet Illinois United States 60435
28 Wolfe Eye Clinic West Des Moines Iowa United States 50266
29 Retina Associates Lenexa Kansas United States 66215
30 Maine Eye Center Portland Maine United States 04101
31 The Retina Care Center Baltimore Maryland United States 21209
32 Retina Group of Washington Chevy Chase Maryland United States 20815
33 Cumberland Valley Retina Associates Hagerstown Maryland United States 21740
34 Retina Specialists Towson Maryland United States 21204
35 Ophthalmic Consultants of Boston Boston Massachusetts United States 02114
36 Foundation for Vision Research Grand Rapids Michigan United States 49546
37 Associated Retinal Consultants PC Royal Oak Michigan United States 48073
38 Vitreo Retinal Surgery Minneapolis Minnesota United States 55435
39 Midwest Vision Research Foundation Chesterfield Missouri United States 63017
40 Sierra Eye Associates Reno Nevada United States 89502
41 Envision Ocular, LLC Bloomfield New Jersey United States 07003
42 Mid Atlantic Retina - Wills Eye Hospital Cherry Hill New Jersey United States 08034
43 Retina Associates of NJ Teaneck New Jersey United States 07666
44 Retina Vit Surgeons/Central NY Liverpool New York United States 13088
45 New York University New York New York United States 10017
46 Western Carolina Retinal Associate PA Asheville North Carolina United States 28803
47 Char Eye Ear &Throat Assoc Charlotte North Carolina United States 28210
48 Duke Eye Center Durham North Carolina United States 27705
49 Cape Fear Retinal Associates Wilmington North Carolina United States 28401
50 Cincinnati Eye Institute Cincinnati Ohio United States 45242
51 The Ohio State University Columbus Ohio United States 43210
52 Retina Vitreous Center Edmond Oklahoma United States 73013
53 Cumberland Valley Retina Consultants; Chambersburg Chambersburg Pennsylvania United States 17201
54 Palmetto Retina Center Florence South Carolina United States 29501
55 Charleston Neuroscience Inst Ladson South Carolina United States 29456
56 Carolina Eyecare Physicians Mount Pleasant South Carolina United States 29464
57 Southeastern Retina Associates Knoxville Tennessee United States 37923
58 Charles Retina Institute Memphis Tennessee United States 38119
59 Tennessee Retina PC Nashville Tennessee United States 37203
60 Retina Res Institute of Texas Abilene Texas United States 79606
61 Texas Retina Associates Arlington Texas United States 76012
62 Austin Retina Associates Austin Texas United States 78705
63 Retina Consultants of Texas Bellaire Texas United States 77401
64 Texas Retina Associates Dallas Texas United States 75231
65 Texas Retina Associates Fort Worth Texas United States 76104
66 Retina & Vitreous of Texas Houston Texas United States 77025
67 Med Center Ophthalmology Assoc San Antonio Texas United States 78240
68 Retina Center of Texas Southlake Texas United States 76092
69 Retina Associates of Utah Salt Lake City Utah United States 84107
70 Rocky Mountain Retina Salt Lake City Utah United States 84107
71 Piedmont Eye Center Lynchburg Virginia United States 24502
72 Wagner Macula & Retina Center Norfolk Virginia United States 23502
73 Retina Institute of Virginia Richmond Virginia United States 23235
74 Retina Center Northwest Silverdale Washington United States 98383
75 Spokane Eye Clinical Research Spokane Washington United States 99204
76 Emanuelli Research and Development Center LLC Arecibo Puerto Rico 00612

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:
NCT04503551
Other Study ID Numbers:
  • GR41675
First Posted:
Aug 7, 2020
Last Update Posted:
Aug 5, 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
Port Delivery System; ranibizumab; Diabetic Retinopathy; anti-VEGF, nonproliferative diabetic retinopathy, retina, vision loss, retinal disease, eye disease
Additional relevant MeSH terms:
Retinal Diseases
Diabetic Retinopathy
Ranibizumab

Study Results

No Results Posted as of Aug 5, 2022